OBJECTIVE To establish a method for simultaneous determination of venetoclax， busulfan and voriconazole in plasma of patients with acute myeloid leukemia （AML）， and apply it clinically. METHODS Plasma samples were subjected to protein precipitation using acetonitrile and subsequently analyzed by liquid chromatography-tandem mass spectrometry （LC-MS/MS） using venetoclax-D 8 ， busulfan-D 8 and posaconazole as internal standards. The separation was performed on a Phenomenex Kinetex ® C 18 column with a mobile phase composed of 0.1% formic acid solution （2 mmol/L ammonium acetate）-0.1% formic acid in acetonitrile （gradient elution） at a flow rate of 0.8 mL/min. The column temperature was set at 40 ℃， the sample size was 5 μL， and the total run time was 3.10 min. An electrospray ionization source was employed， and positive ion scanning was conducted using multiple reaction monitoring mode. The ion pairs used for quantitative analysis included m/z 868.4→636.3 （venetoclax）， m/z 264.1→151.1 （busulfan）， and m/z 350.1→224.0 （voriconazole）. The above LC-MS/MS method was adopted to determine plasma concentrations of venetoclax and voriconazole in 10 AML patients， as well as plasma concentration of busulfan in 5 patients undergoing conditioning treatment for allogeneic hematopoietic stem cell transplantation. RESULTS The linear ranges of venetoclax， busulfan and voriconazole were 50-10 000， 15-3 000 and 50-10 000 ng/mL， respectively （ R 2 ≥0.999 0）， with lower limits of quantification of 50， 15 and 50 ng/mL， respectively. The RSDs of intra-day and inter-day precision tests for all three analytes were all less than 10%， with accuracy （relative errors） ranging from －10.00% to 12.96%. The average extraction recovery ranged from 92.54% to 100.95%， and the average matrix effect was 89.98%-101.49%. Dilution reliability covered all dilution factors used in the test samples， and the absolute values of relative errors in stability tests were all≤16.25%. The plasma concentrations of venetoclax， busulfan and voriconazole in enrolled patients were 496.20-4 250.45， 233.48-2 002.28 and 475.51-5 710.18 ng/mL， respectively. CONCLUSIONS The LC-MS/MS method established in this study is rapid， sensitive and easy to operate， and can be used for the therapeutic drug monitoring of venetoclax， busulfan and voriconazole.

Objective To summarize the whole process comprehensive management experience in transfemoral aortic valve replacement(TF-TAVR)using self-expanding valve in 79 patients with pure native aortic valve regurgitation(PNAR).Methods The nursing team adopted a multi-team collaboration approach.Preoperative nursing assessment and full preparation,enhanced psychological support,and sleep management were carefully carried out;during the operation,nurses well cooperated with doctor,implemented predictive care and intervention for possible complications;and after surgery the hemodynamics and respiratory functions were closely monitored to promptly detect and manage the complications,and to implement the infection prevention cluster management process and discharge preparation services.Besides,the comprehensive management measures throughout the entire process,the occurrence of complications and corresponding nursing responses,as well as the six-minute walk test before and after the operation were recorded.The Discharge Readiness Scale was used to evaluate the implementation of patient discharge readiness services so as to check the implementation effect of the comprehensive whole process management measures.Results Through the implementation of comprehensive whole process management measures,the surgery-related ventricular fibrillation and cardiac arrest obtained accurate and timely treatment,no newly-developed complications such as deep vein thrombosis of lower limbs occurred.Through the implementation of infection cluster nursing measures,the incidence of pulmonary infection in patients decreased from 52.00％in the early stage of carrying out the management measures to 9.26％.Through the implementation of discharge preparation services and continuous quality improvement,the left ventricular ejection fraction(LVEF)value in 64 patients receiving successful TAVR increased from(44.06±5.51)％to(54.67±5.20)％,and the difference was statistically significant(t=19.634,P＜0.001).On the day of discharge,the six-minute walk test distance increased from preoperative(131.39±39.36)meters to postoperative(180.77±29.72)meters,and the difference was statistically significant(t=10.898,P＜0.001).The average self-assessment score of discharge readiness of patients was(7.33±1.41)points.All patients were well recovered when discharged from hospital.Conclusion According to the different surgical key points and the difficult problems,full and effective implementation of comprehensive whole process management measures can ensure that the PNAR patients are able to smoothly pass through the perioperative period and obtain a satisfactory recovery after receiving TF-TAVR.

Objective To establish an UPLC-MS/MS method for determinating content of three paclitaxel fatty acid esters such as paclitaxel myristate(PTX-MA),paclitaxel palmitate(PTX-PA)and paclitaxel myristate(PTX-SA)in mouse plasma,and preliminarily investigate the pharmacokinetic characteristics of their liposomes in mice.Methods Eclipse Plus C8 chromatography column(2.1 mm×50 mm,1.8 μm)was used with different proportions of 0.2%formic acid aqueous solution(A)and methanol(B)mixture as mobile phase for gradient elution at a flow rate of 0.3 ml/min.The collum temperature was 30℃.The sample injection volume was 10 μl.The triple quadrupole mass series spectrometer was used as multi-reaction monitoring(MRM).Results PTX-MA,PTX-PA and PTX-SA all exhibited a good linear relationship in the range of 5.0～500.0 ng/ml(r>0.995 0).Their RSD of precision,stability,extraction recovery rate and matrix effect test results was all less than 10%.The half-lives(t1/2)for liposomes of three paclitaxel fatty acid esters PTX-MA-L、PTX-PA-L and PTX-SA-L in mice were 14.78 h,44.49 h and 69.32 h individually,and their clearance rates(CL)were 29.06 L?kg/h,24.94 L?kg/h and 13.74 L?kg/h,respectively.Conclusion This method had high specificity,sensitivity,easy operation and good stability,which could be used for the determination of paclitaxel fatty acid esters in mouse plasma.The results of pharmacokinetic studies in mice showed that t1/2 for paclitaxel fatty acid esters were significantly prolonged,and the clearance rate were significantly reduced with the length of fatty acid carbon chains increasement,which indicated that esterification of paclitaxel with different chain length saturated fatty acids could obviously alter its in vivo pharmacokinetic properties,which provided scientific basis for the research and development of nano formulations of paclitaxel fatty acid ester prodrug.

Objective To improve the cellular uptake efficiency and the therapeutic effect through the structural modification of paclitaxel(PTX)and the preparation of corresponding liposomes.Methods The prodrug of paclitaxel,PTX-PA,was prepared by esterification reaction,and the quantitative detection method of PTX-PA was established.Next,the optimal formulation and preparation of PTX-PA/Lip was obtained through single factor screening based on their appearance,particle size,and encapsulation efficiency.Results The PTX-PA was successfully synthesized,and the established HPLC quantitative analysis method for PTX-PA met the methodological requirements.After the optimal preparation and formulation research through single factor screening,the particle size of optimized PTX-PA/Lip was(62.75±1.81)nm with a PDI of(0.076±0.02),while the drug encapsulation rate reached more than 90%.Conclusion This research successfully prepared palmitic acid modified paclitaxel liposomes based on nanotechnology,enhancing the drug delivery efficiency of paclitaxel and laying the foundation for the pharmacodynamics research of PTX-PA.

Objective:To explore the clinical characteristics of anaphylaxis caused by gonadorelin in children in gonadotropin-releasing hormone (GnRH) stimulation test.Methods:The research subjects were children aged ≤14 years who experienced anaphylaxis using gonadorelin in the Chengdu Adverse Reaction Center database from January 1, 2015 to December 31, 2021. The purpose of medication was GnRH stimulation test. Through the hospital information system, the children′s basic information, usage of gonadorelin, occurrence of severe allergic reactions, and treatments and outcomes of anaphylaxis were collected and retrospectively analyzed.Results:A total of 14 cases of anaphylaxis in children caused by gonadorelin in the GnRH stimulation test were collected, including 3 males and 14 females, with an age of (9±2) years. All 14 cases were evaluated with a score of ≥5 using the Naranjo evaluation method. The dose of gonadorelin in the 14 children was (2.55±0.09) μg/kg and the drug was all given by intravenously injection; anaphylaxis occurred in 4 children during the first GnRH stimulation test and in 10 children during the second GnRH stimulation test. The time from medication to anaphylaxis occurence was (6.0±3.5) minutes. The symptoms of anaphylaxis in 14 children were systemic allergic reactions, involving various systems throughout the body. All children had 3 or more types of systemic damage. After anaphylaxis occurrence, gonadorelin was discontinued in all 14 patients; 5 received intramuscular injection of adrenaline, 5 received intravenous injection of adrenaline, 1 received intravenous injection of isoprenaline and intramuscular injection of adrenaline, and 3 received intravenous injection of dexamethasone only. After treatments, all children were improved.Conclusions:Anaphylaxis caused by gonadorelin in children is a rare but severe adverse reaction, and the drug may have a possibility of cross allergy with GnRH analogues. Therefore, when diagnosing and treating precocious puberty in children, medication should be given under monitoring conditions.

Objective:To explore the clinical characteristics of anaphylaxis caused by gonadorelin in children in gonadotropin-releasing hormone (GnRH) stimulation test.Methods:The research subjects were children aged ≤14 years who experienced anaphylaxis using gonadorelin in the Chengdu Adverse Reaction Center database from January 1, 2015 to December 31, 2021. The purpose of medication was GnRH stimulation test. Through the hospital information system, the children′s basic information, usage of gonadorelin, occurrence of severe allergic reactions, and treatments and outcomes of anaphylaxis were collected and retrospectively analyzed.Results:A total of 14 cases of anaphylaxis in children caused by gonadorelin in the GnRH stimulation test were collected, including 3 males and 14 females, with an age of (9±2) years. All 14 cases were evaluated with a score of ≥5 using the Naranjo evaluation method. The dose of gonadorelin in the 14 children was (2.55±0.09) μg/kg and the drug was all given by intravenously injection; anaphylaxis occurred in 4 children during the first GnRH stimulation test and in 10 children during the second GnRH stimulation test. The time from medication to anaphylaxis occurence was (6.0±3.5) minutes. The symptoms of anaphylaxis in 14 children were systemic allergic reactions, involving various systems throughout the body. All children had 3 or more types of systemic damage. After anaphylaxis occurrence, gonadorelin was discontinued in all 14 patients; 5 received intramuscular injection of adrenaline, 5 received intravenous injection of adrenaline, 1 received intravenous injection of isoprenaline and intramuscular injection of adrenaline, and 3 received intravenous injection of dexamethasone only. After treatments, all children were improved.Conclusions:Anaphylaxis caused by gonadorelin in children is a rare but severe adverse reaction, and the drug may have a possibility of cross allergy with GnRH analogues. Therefore, when diagnosing and treating precocious puberty in children, medication should be given under monitoring conditions.

To present the clinical characteristics and the misdiagnosis rate of acute coronary syndrome manifested primarily as throat discomfort, we conducted a multicentric and retrospective study in the cardiology and otorhinolaryngology departments. Records of patients with primary complaint of throat discomfort, absence of chest pain at onset, and an ultimate diagnosis of acute coronary syndrome, as well as patients with pharyngitis (as controls) were collected from May 2015 to April 2016. The patients' main manifestations were compared. Logistic regression results showed that chest tightness, dyspnea, perspiring, and exertional throat symptoms were significantly associated with acute coronary syndrome, with odds ratios of 8.3 (95% CI 2.2-31.5), 10.9 (95% CI 1.8-66.9), 25.4 (95% CI 3.6-179.9), and 81.2 (95% CI 13.0-506.7). A total of 25 (56.82%) out of 44 acute coronary syndrome patients, who were first admitted to the otorhinolaryngology department, were misdiagnosed, with a 12% (3/25) mortality rate. Throat discomfort can be the principal manifestation of acute coronary syndrome. Such patients exhibit high misdiagnosis and mortality rates. Exertional throat symptoms, chest tightness, perspiring, and dyspnea were important indicators of acute coronary syndrome in patients whose main complaint was throat discomfort. The awareness of this condition will result in prompt diagnosis and reduce morbidity and mortality.
Acute Coronary Syndrome/etiology* ; Dyspnea/etiology* ; Humans ; Pharyngitis/diagnosis* ; Pharynx ; Retrospective Studies

Colorectal cancer is a malignant tumor with increasing incidence in China. Chemotherapy or neoadjuvant therapy are needed when the patients have deep tumor invasion of distant metastasis due to the hidden clinical manifestations and limited screening methods for the colorectal cancer. With many side effects of the current chemo-medications and the drug resistance, researchers are actively exploring new chemotherapy drugs for colorectal cancer. Paclitaxel is a first-line chemotherapy drug for the treatment of breast cancer, ovarian cancer, pancreatic cancer and other malignant tumors. Colorectal cancer cells are prone to become resistant to paclitaxel and the treatment efficiency was limited. However, new drug delivery systems and the combination drug therapy can enhance the treatment efficiency. This article reviews the effective treatment strategies of paclitaxel for colorectal cancer with the hope for new ideas and more effective chemotherapy.

Objective:To investigate the effect of enhanced recovery after surgery (ERAS) in percutaneous pedicle screw internal fixation treating thoracolumbar fracture patients.Methods:A retrospective case-control study was conducted to analyze the clinical data of 62 patients with thoracolumbar fracture treated by percutaneous pedicle screw internal fixation at Second Hospital of Soochow University from October 2018 to April 2019. There were 42 males and 20 females, aged 27-59 years (mean, 43.9 years). Fracture site included T 11 in 4 patients, T 12 in 28, L 1 in 23 and L 2 in 7, and AO type contained type A1 in 40 patients, type A2 in 3, and type A3 in 19. Thirty-one patients were treated with ERAS nursing mode (ERAS group), and other 31 patients with routine nursing mode (control group). The postoperative recovery time of intestinal function, first time of expelling flatus and dejection time, hospitalization time, preoperative and postoperative pain visual analogue scale (VAS), Kolcaba comfort scale (GCQ), Oswestry disability index (ODI), incidence of abdominal distension, incidence of urinary tract infection, first wake up dizziness, urinary retention, and wound healing were compared between the two groups. Results:Period of follow-up for all patients was 3-6 months (mean, 4.5 months). Postoperative recovery time of intestinal function, first time of expelling flatus and dejection time in ERAS group were (7.2±2.0)hours, (10.7±3.7)hours and (26.7±6.4)hours, respectively, which were significantly decreased compared to control group [(19.2±5.6)hours, (22.5±5.1)hours, (72.5±12.4)hours] ( P<0.05). Hospitalization time was (4.7±1.3)days in ERAS group, shorter than that in control group [(5.9±1.5)days]. There was no significant difference in VAS preoperatively between the two groups ( P>0.05). VAS in ERAS group was (3.6±1.5)points, (2.8±0.8)points, (1.7±0.6)points at postoperative 1, 3 and 7 days, lower than that in control group [(4.6±1.3)points, (4.0±1.3)points, (2.7±0.9)points] ( P<0.05). GCQ score in ERAS group was (72.0±6.5)points, (75.0±11.1)points, (88.4±5.1)points and (89.3±4.5)points at 2 hours before operation and 2 hours, 1 days and 3 days after operation, which were higher than that in control groups [(54.0±7.2)points, (59.5±6.3)points, (62.7±5.9)points, (76.0±5.7)points] ( P<0.05). ODI in ERAS group was 37.3±5.8, 28.9±6.3 and 23.1±2.7 at 3 days, 1 month and 3 months after operation, which was markedly decreased compared to control group (44.9±7.9, 33.9±8.7, 30.3±5.3) ( P<0.05). Moreover, the incidence of abdominal distension, urinary tract infection and first wake up dizziness in ERAS group was 7%, 5%, 3%, respectively, reduced from that in control group (26%, 35%, 16%) ( P<0.05). No significant difference was observed in urinary retention wound healing of the two groups, but there was no difference in wound healing ( P>0.05). Conclusion:For thoracolumbar fracture patients treated with percutaneous pedicle screw internal fixation, ERAS has advantages over traditional nursing in attenuating pain, shortening hospitalization time, reducing postoperative abdominal distension and urinary tract infection, and accelerating functional recovery.

Objective To synthesize a lipophilic prodrug of triptolide (TP) and improve its druggability .Methods Trip-tolidestearate (TP-SA)was synthesized via the DMAP-catalyzed DCC method and identified by MS ,1H-NMR and 13C-NMR. The shake-flask method was used to study the oil/water partition coefficient .The preparations of TP and TP-SA liposomes and emulsions were compared .Their encapsulation efficiency and stability were investigated .Results TP-SA was synthesized suc-cessfully .Its log P in octanol/water system was 2 .33 .It was difficult to prepare TP liposome or emulsion .By contrast ,TP-SA liposome and emulsion can be prepared successfully with the same formulation process .The particle size of TP-SA lipo-somes were about 90 nm and TP-SA emulsions were about 110 nm .The encapsulation efficiency was above 95% .Their stabili-ty were studied at 4℃ and 25℃ .The preparation parameters ,such as particle size and encapsulation efficiency ,had no signif-icant change in a week .Conclusion Triptolide stearate enhanced drug lipophilicity .Its druggability was improved significant-ly .These data can be used for the TP related drug design and development .