OBJECTIVE To standardize the use of sterile powder for injection redissolution solvent and intravenous drugs diluent solvent， and ensure the safety of clinical drug use. METHODS The intravenous drug resolvent generation system and the intravenous drug solvent incompatibility rules library were constructed and operated by prescription-checking pharmacist team in our hospital by formulating a list of intravenous drugs needed to be dissolved with sterilized water for injection and a contraindication list of intravenous solvent compatibility. The unreasonable medical orders reviewed and intervened in our hospital from January to April 2023 （before the implementation of the intravenous drug solvent incompatibility rules library） and from May to August 2023 （after the implementation） were analyzed statistically to compare the number of unreasonable solvent selection orders， interception rate， and the success rate of pharmacists’ interventions for unreasonable solvent selection orders before and after the implementation. RESULTS Before the implementation of the solvent incompatibility rules library， a total of 5 229 groups of medical orders with unreasonable solvent selection in our hospital were identified， among which there were 1 204 groups of seriously unreasonable medical orders， with interception rate of 23.03% and the success rate of pharmacists’ intervention of 15.90%. After the implementation of the solvent incompatibility rules library， the total number of medical orders with unreasonable solvent selection was 3 258 groups， among which there were 1 148 groups of seriously unreasonable medical orders， with interception rate of 35.24% and success rate of pharmacists’ intervention of 24.83%， being significantly higher than before implementation （P＜0.01 or P＜0.001）. CONCLUSIONS The establishment and application of the intravenous drug resolvent generation system and the solvent incompatibility rules library can significantly increase the interception rate of unreasonable solvent selection orders and the success rate of pharmacists’ interventions, and ensure the safety of clinical drug use.

To identify the bitter compounds of real-world Xiaoer Ganmao Oral Liquid sugar-free intermediates, an integrated strategy has been developed by using ultra-high performance liquid chromatography with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MSⁿ) method and BitterX database prediction. The chromatographic operating conditions were as follows, chromatographic column: Acquity UPLC BEH C₁₈ (100 mm × 2.1 mm, 1.7 μm), mobile phase: 0.1% formic acid-water solution (A)-acetonitrile (B) with gradient elution. The data were collected in positive and negative ion modes, respectively. The accurate molecular mass and structural information of the target compounds were obtained based on quasi-molecular ions and fragmentation ions provided by high-resolution mass spectrometry. The compounds were identified by combining retention time, reference substances, reports, and other relevant data, and a total of 57 constituents including flavonoids, alkaloids, and phenylpropanoids were finally identified. Further, the BitterX database was used to predict binding probability of compounds to bitter receptors and identify potential bitter critical quality attributes, finally 33 potential bitter compounds, including kukoamine A and linarin, were predicted. This study comprehensively characterized the material basis of Xiaoer Ganmao Oral Liquid sugar-free intermediates, it provides an effective method for bitter compound screening and a reference for further improving the undesirable taste of Xiaoer Ganmao Oral Liquid.

OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.
Humans ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Mutation ; Leukemia, Myeloid, Acute/drug therapy* ; Nucleophosmin ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Receptors, GABA/therapeutic use*

Humans ; Gemcitabine ; Neoplasms

Objective:To study the risk factors and prediction model of radiation pneumonitis (RP) after radical chemoradiotherapy for locally advanced esophageal cancer based on dosiomics.Methods:Clinical data of 105 patients with esophageal cancer undergoing radical chemoradiotherapy at Zhejiang Cancer Hospital between January 2020 and August 2021 were retrospectively analyzed. RP was scored using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTCAE 5.0). Clinical factors, traditional dosimetric features and dosiomics features were collected, respectively. The features for predicting PR were analyzed by limma package. Support vector machine, k-nearest neighbor, decision tree, random forest and extreme gradient boosting were used to establish the prediction model, and the ten-fold cross-validation method was employed to evaluate the performance of the model. The differences of this model when different features were chosen were analyzed by delong test.Results:The incidence of RP in the whole group was 21.9%. One clinical factor, 6 traditional dosimetric features and 42 dosiomics features were significantly correlated with the occurrence of RP (all P<0.05). Support vector machine using linear kernel function yielded the optimal prediction performance, and the area under the receiver operating characteristic (ROC) without and with dosiomics features was 0.72 and 0.75, respectively. The models established by support vector machine, random forest and extreme gradient boosting were significantly different with and without dosiomics features (all P<0.05). Conclusion:The addition of dosiomics features can effectively improve the performance of the prediction model of RP after radiotherapy for esophageal cancer.

OBJECTIVE: To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study. METHODS: A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators. RESULTS: A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (P_trend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death. CONCLUSIONS In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Objective:To investigate the prognostic factors of patients with esophageal squamous cell carcinoma with pulmonary metastasis.Methods:Clinical characteristics of 135 esophageal squamous cell carcinoma patients presenting with pulmonary metastasis after treatment in Zhejiang Cancer Hospital from 2008 to 2018 were retrospectively analyzed. Thesurvival rate was calculated by Kaplan-Meier method. Univariate analysis was performed by log-rank test. Multivariate prognostic analysis was conducted by Cox models.Results:The median follow-up time of 135 patients with esophageal squamous cell carcinoma was 94.2 months (19.5-258.9 months), and 109 patients died (80.7%). The 1-and 2-year overall survival rates were 47.4% and 25.1%, with the median survival time was 11.1 months (7.3-14.9 months). Univariate prognostic analysis showed that age, number of lung metastases, treatment of lung metastases, lymph node metastasis, distant organ metastasis, and the interval between the first treatment and lung metastasis were the prognostic factors of esophageal squamous cell carcinoma with lung metastasis (all P<0.05). Multivariate analysis demonstrated that age and number of lung metastases were the independent prognostic factors for patients with esophageal squamous cell carcinoma with lung metastases (all P<0.05). Conclusions:Age and number of lung metastases are the independent prognostic factors for patients with esophageal squamous cell carcinoma with lung metastases. Surgery or radiotherapy-based regional therapy can enhance clinical prognosis.

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

COVID-19/genetics* ; Genome, Viral/genetics* ; Humans ; RNA, Viral/genetics* ; RNA-Seq ; SARS-CoV-2/genetics* ; Whole Genome Sequencing

By systematically sorting out the ancient medical books and modern clinical literature of Yiguanjian， the historical evolution of this formula， including its source， composition， origin， processing， dosage， preparation and usage， functions and indications， evolution of prescription meaning， is textual so as to clarify the historical evolution and clinical application of Yiguanjian. On the basis of fully considering the actual demand of development of famous classical formula preparation and the usage habit of modern clinical practice， the feasible development suggestions were put forward. Yiguanjian is composed of six herbs， which is derived from Yifang Jiedu (《医方絜度》) . It is an ancient book of traditional Chinese medicine edited by QIAN Min-jie in Qing dynasty. The original medicinal plants and medicinal parts of the formula were basically the same as those recorded in the 2020 edition of Chinese Pharmacopoeia. The raw products should be selected for decoction pieces and processed according to the methods recorded in the 2020 edition of Chinese Pharmacopoeia. The reference dose of the medicine in this formula is set out in Yifang Jiedu. According to dosage of one Qian（钱）=3.73 g， the dosages of Glehniae Radix， Ophiopogonis Radix and Angelicae Sinensis Radix were 5.60 g， the dosages of Lycii Fructus and Rehmanniae Radix were 11.19 g， the dosage of Toosendan Fructus was 7.46 g. These decoction pieces were boiled and warm decoction was taken. According to ancient medical records， the formula always has the effect of nourishing Yin and relieving Qi of liver. It is used to treat syndrome of stagnation of liver-Qi and deficiency of liver-Yin and kidney-Yin， which can be seen with pain in chest， stomach and flank， acerbity and vomiting， dry throat and mouth， red tongue， weak pulse or deficiency of string and hernia. Here， the source， processing and others of Yiguanjian were clarified， providing a literature reference for the development and application of this famous classical formula.