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 investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

The PCR-amplified severe fever with thrombocytopenia syndrome virus(SFTSV)Gn-DⅢ-Ⅲ gene was inserted into the pET-30a(+)prokaryotic expression vector to generate the re-combinant plasmid pET-SFTSV-Gn-D Ⅲ-Ⅲ.The plasmid was transformed into E.coli BL21(DE3)for Gn-DⅢ-m protein expression and the expression conditions were optimized.The Gn-DⅢ-Ⅲ protein purified with Ni-NTA column affinity chromatography was applied as the captured antigen to establish an indirect ELISA method for the detection of SFTSV antibody.The results demonstrated that the recombinant plasmid pET-SFTSV-Gn-D Ⅲ-Ⅲ was successfully constructed as identified by PCR and sequencing.The recombinant protein SFTSV Gn-D m-Ⅲ was soluble ex-pression in E.coli under the optimal induction conditions of 0.4 mmol/L IPTG at 25 ℃ for 4 h,and the protein purity was 91.77％after purification by Ni-NTA column.The optimal reaction con-ditions for the indirect ELISA of SFTSV antibody were as follows:coating antigen concentration(5 μg/mL),primary antibody(incubation at 37 ℃ for 1.5 h),and secondary antibody(diluted 1:10 000 and incubated at 37 ℃ for 1 h).The established method had no cross-reactivity with Rift Valley fever virus(RVFV),Ebola virus(EBOV),and tick-borne encephalitis virus(TBEV)posi-tive sera.The method had a high sensitivity,with P/N＞2.1 for SFTSV-positive sera diluted to 81920.Coefficients of variation for intra-and inter-batch reactions were less than 10％.Detection of four SFTSV-infected human clinical serum samples showed the serum samples from patients in re-mission were tested as positive(P/N＞2.1),while serum samples from patients with multiple or-gan failure were detected as negative(P/N＜2.1).The results indicated that the SFTSV Gn-D Ⅲ-Ⅲ protein was successfully expressed and purified,and it was used as the coating protein to estab-lish an indirect ELISA assay for SFTSV antibody,which possesses good specificity,sensitivity and reproducibility.This method might be applied to detect human SFTSV clinical serum samples.

Objective    To investigate the feasibility and safety of DynaCT microwave ablation (MWA) guided by 3D iGuide puncture technology for lung cancer. Methods    The clinical data of 19 patients with primary or metastatic lung cancer who underwent DynaCT MWA from June 2019 to December 2020 in our hospital were retrospectively analyzed, including 15 males and 4 females with an average age of 64.9±11.7 years. The technical success rates, adverse reactions and complications, postoperative hospital stay, and local therapeutic efficacy were recorded. Results    Technical success rate was 100.0%. The mean time required to target and place the needle was 15.7±3.7 min and the mean ablation time was 5.7±1.6 min. Thirteen patients underwent biopsy synchronously before the ablation, and 10 (76.9%) patients had positive pathological results. The main adverse reactions were pain (7/19, 36.8%), post-ablation syndrome (4/19, 21.1%) and cough (2/19, 10.5%). The minor complications were pneumothorax (6/19, 31.6%), hemorrhage (5/19, 26.3%), pleural effusion (2/19, 10.5%) and cavity (1/19, 5.3%). Three patients had moderate pneumothorax and received closed thoracic drainage. The median hospitalization time after ablation was 2.0 (2.0, 3.0) d, and no patient died during the perioperative period. The initial complete ablation rate was 89.5% (17 patients) and the incomplete ablation rate was 10.5% (2 patients) at 1-month follow-up, and no local progression was observed. Conclusion    DynaCT MWA of lung cancer under the guidance of 3D iGuide system is safe and feasible with a high short-term local control rate, but the long-term efficacy remains to be further observed.

Objective: To investigate the effect of acid-sensing ion channel 1 (ASIC1) gene knockout on articular cartilage injury in adjuvant arthritis (AA) of mice． Methods: Wild-type mice and ASIC1 knockout mice were divided into normal group and model group．Arthritis score was performed by observing the inflammation of paws，and the right paw swelling was measured．HE staining，immunohistochemistry，TUNEL and ELISA were used to detect the injury of articular cartilage and arthritic inflammation. Results : The arthritis score and paw swelling of AA mice with ASIC1 knockout was lower than that of the AA wild-type mice．AA mice with ASIC1 knockout showed less destruction and increased expression of collagen-Ⅱin articular cartilage． Moreover ，the lower apoptosis rate was observed by TUNEL assay in AA mice with ASIC1 knockout by comparing with AA wild-type mice．Furthermore，ELISA assay showed that the levels of IL-1 β、TNF-α in the serum decreased in AA mice with ASIC1 knock- out． Conclusion Knockout of ASIC1 may have protective effect on articular cartilage injury.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

Objective:To examine the influence of acute hypoxemia on central venous pressure (CVP) and diastolic blood pressure (DBP) in critical patients assisted by mechanical ventilation.Methods:We retrospectively analyzed the clinical data of critical patients assisted by mechanical ventilation in Medical Information Mart for Intensive Care Ⅲ (MIMIC-Ⅲ) database. Influence of acute hypoxemia on CVP and diastolic blood pressure (DBP) were evaluated. Hypoxemia was defined according to oxygenation index (OI) (OI≤100 as severe, 100

Objective    To evaluate the safety and efficacy of microwave ablation (MWA) in the treatment of lung tumors. Methods    The clinical data of 31 patients with lung neoplasms treated with MWA from January 2019 to August 2020 in a single center were retrospectively analyzed. There were 17 males and 14 females at an age of 63.4±10.4 years. The characteristics of the lesions, technical success rate, technical efficiency, local progression rate, adverse reactions and complications were recorded in detail. Results    There were 39 target lesions with an average diameter of 20.2±10.6 mm. A total of 36 MWA procedures were completed. The initial technical success rate was 84.6% (33/39), and the technical efficiency was 92.3% (36/39). The median postprocedure hospital stay was 2.0 (2.0, 3.0) d. A total of 12.9% (4/31) of the patients had local progression, and the local control rate was 87.1%. The main adverse reactions were pain (12/36, 33.3%), cough (6/36, 16.7%), post-ablation syndrome (6/36, 16.7%) and pleural effusion (3/36, 8.3%). The main complications were pneumothorax (11/36, 30.6%), hemorrhage (8/36, 22.2%), cavitation (2/36, 5.6%) and pulmonary infection (1/36, 2.8%). The median follow-up time was 13.0 (8.0, 18.0) months. No patient died during the follow-up. Conclusion    MWA is safe and effective in the treatment of lung tumors with controllable complications. Successive researches with large sample, and medium and long-term follow-ups are needed to explore the significance of combined therapies.

OBJECTIVE: To investigate the effect of working time on the prognosis of patients with ischemic stroke undergoing intravenous thrombolysis. METHODS: Clinical data of 3050 patients with ischemic stroke received intravenous thrombolysis from 71 hospitals in Zhejiang Province during June 2017 and September 2018 were retrospective analyzed. Whole day of Saturday and Sunday were defined as weekend; whole day of Monday to Friday were defined as weekdays; Monday to Friday 8:00-17:00 were defined as daytime of weekdays; Monday to Friday 17:01-07:59 on next day were defined as nights of weekdays; unconventional working time were defined as weekend and nights of weekdays. Good outcome was defined as mRS 0-2 at 3 months. Univariate analyses of baseline and prognostic variables in group of weekend and weekdays, nights of weekdays and daytime of weekdays, unconventional working time and daytime of weekdays were performed. Binary logistic regression was used to investigate whether weekend, nights of weekdays and unconventional working time were independent predicting factors of outcome after intravenous thrombolysis, respectively. RESULTS: There was no difference in 7-day mortality, 3-month mortality and good outcome at 3-month between weekend group and weekdays group, nights of weekdays group and daytime of weekdays group, unconventional working time group and daytime of weekdays group (all >0.05). Binary logistic regression results showed that weekends, nights of weekdays and unconventional working time were not independent predicting factors for outcome after intravenous thrombolysis (all >0.05). CONCLUSIONS The working time has not affected the outcomes of patients with ischemic stroke undergoing intravenous thrombolysis in studied hospitals of Zhejiang province.
Brain Ischemia ; drug therapy ; Humans ; Prognosis ; Retrospective Studies ; Stroke ; drug therapy ; Thrombolytic Therapy ; Time Factors

Objective To evaluate the clinical value of endoscopic submucosal tunnel dissection ( ESTD) for treatment of large gastric angle superficial neoplasms. Methods A retrospective analysis was performed on data of 87 patients with superfical neoplasms in gastric angle, including 32 cases undergoing ESTD and 55 cases undergoing endoscopic submucosal dissection ( ESD) in 6 institutions between July 2014 and July 2016. The dissection time, dissection speed, en bloc resection rate, curative resection rate, adverse events, and prognosis were compared between the two groups. Results The ESTD group showed a shorter dissection time ( 87. 3 ± 32. 6 min VS 136. 7 ± 64. 5 min, P<0. 01 ) , a higher dissection speed ( 0. 18 ± 0. 07 cm2/min VS 0. 08±0. 05 cm2/min, P<0. 01), a higher en bloc resection rate[100％ (32/32) VS 87. 3％ (48/55), P=0. 035], and a higher curative resection rate[100％ (32/32) VS 85. 5％ (47/55), P=0. 024] compared with the ESD group. The intraoperative bleeding rate[59. 4％ (19/32) VS 100. 0％( 55/55) , P<0. 01] and muscular injury rate[ 0 ( 0/32) VS 14. 5％ ( 8/55) , P=0. 024] were lower in the ESTD group than those of the ESD group. There was no statistical difference on recurrence rate between the two groups[0 (0/32) VS 1. 9％ (1/54), P=0. 443]. Conclusion ESTD has a higher dissection speed and greater security on treatment of large gastric angle superficial neoplasms, and is worthy to be generalized.