Research progress of needle-free injection technology / 药学学报

Needle-free injection technology (NFIT) refers to the drug delivery systems in which drugs are propelled as high-speed jet streams using any of the pressure source to penetrate the skin to the required depth. NFIT is a promising drug delivery system as it enables the injection of liquids, powders, and depot/projectiles, and has the advantages of preventing needle stick accidents, improving drug bioavailability, eliminating needle-phobia, increasing vaccine immunity, simplifying operations and is convenient for patients to use. NFIT and its research background, the structure and classification of needle-free jet injectors (NFJI), drugs that can be delivered using NFJI and the factors affecting the injection effect are comprehensively reviewed in this paper. The limitations and potential development directions are summarized to provide a theoretical basis for the application and development of NFIT.

The Practice of Cross-Cultural Medical Services in the United States and Its Enlightenment to China / 中国医学伦理学

This paper collected and sorted out the cross-cultural medical practice in the top 20 US hospitals in 2019-2020 through web surveys, and summarized the concepts, featured projects and models of cross-cultural medical services in American hospitals. Generally, hospitals in the US advocate the service concept of "patient-centered", provide full-process services before, during and after the treatment, involving appointments, accommodation, transportation, language translation, medical process management, etc., and attach great importance to the role of culture factors in medical treatment and cross-cultural medical education and training for employees. On this basis, it is proposed that Chinese medical institutions should focus on the following aspects in the development of foreign-related medical services: conform to international medical service concepts and standards, improve the cross-cultural medical competence of medical staff and other groups, explore cross-cultural medical service models with localized characteristics, and build the international image of the hospital with the construction of international environment.

Research on Cross-cultural Competence of Medical Staff and Its Cultivation Path / 中国医学伦理学

With the acceleration of globalization, the number of foreigners in China is rising year by year, and their demand for medical treatment is also increasing. It is imperative to strengthen the supply of international professional medical services in China and improve the cross-cultural competence of medical staff. As the origin of cross-cultural medical competence research, the United States has accumulated rich theoretical and practical experience. By defining the concept and connotation of cross-cultural competence in the medical context and explaining its constituent elements, based on the experience of the United States and combined with the actual situation of China, this paper put forward that the cultivation path of cross-cultural competence of medical staff should be explored from the aspects of enhancing cross-cultural awareness of medical staff, strengthening cross-cultural medical competence training, and utilizing a variety of measures and tools.

Content measurement of doxorubicin hydrochloride and lonidamine by HPLC / 药学实践杂志

Objective To establish a method for the simultaneous determination of DOX·HCl and LND. Methods HPLC was performed on Agilent 5 HC-C18（2） （4.6 mm × 250 mm, 5 µm） column. The mobile phase was methanol-0.1% TFA aqueous solution, and the gradient elution procedure were: 0 to 3 min, 65% methanol; 3 to 7 min, 65%→90% methanol; 7 to 13 min, 90% methanol; 13 to 15 min, 90%→65% methanol; 15 to 20 min, 65% methanol. The collection time was 20 min, the balance time was 3 min, the UV detection wavelengths were 205 nm and 253 nm. The flow rate was 1.0 ml/min and the column temperature was 35℃. The amount of inlet was 10 µl. Results The method was highly specific, and both DOX·HCl and LND exhibited good linearity in the concentration range of 1-40 µg/ml and 6-240 µg/ml, respectively. The two compounds’ precision, stability, and recovery satisfied the requirements of the method. Conclusion This study established a HPLC method that was suitable for the simultaneous detection of DOX·HCl and LND. This method’s high level of specificity, accuracy, and reliability .

Preparation and pharmacokinetics of flumazenil sublingual tablet / 药学实践杂志

Objective To prepare flumazenil sublingual tablets and study its bioavailability. Methods Flumazenil sublingual tablets were prepared by compressing flumazenil inclusion compound with hydroxypropyl-β-cyclodextrin as the inclusion material. In a double-cycle crossover trial, twelve beagle dogs were randomly divided into two groups, one group receiving flumazenil sublingual tablets and the other receiving flumazenil injections. LC-MS method was developed and validated to determine flumazenil plasma concentration. The pharmacokinetic parameters and bioavailability were calculated using WinNonlin pharmacokinetic software. Results In the pharmacokinetic study, AUClast of flumazenil injection and sublingual tablet was （8.41±2.15） and （8.86±2.83） h·ng·ml−1, respectively; Cmax was （10.96±2.62） and （6.36±2.14） ng/ml, respectively; tmax was （0.18±0.05） and （0.58±0.24） h, respectively. The bioavailability of flumazenil sublingual tablet was 52.68%. Conclusion Clathrates were used to prepare flumazenil sublingual tablets to achieve safe and efficient delivery. LC-MS method was established for the determination of flumazenil plasma concentration, and the advantages were simple, accurate and sensitive.

Preparation and cytotoxicity of doxorubicin-containing gold nanoparticles / 药学实践杂志

Objective To construct methoxy polyethylene glycol (mPEG) modified gold nanoparticles (AuNPs) loaded with doxorubicin (DOX) AuNPs-mPEG@DOX in order to reduce the toxicity and side effects of DOX. Methods AuNPs-mPEG@DOX was prepared and characterized by Z-Average, Zeta potential and UV-Vis spectroscopy. The impact of thiol-linked DOX (HS-DOX) at various dosage concentrations on the drug adsorption rate and drug loading of AuNPs-mPEG@DOX was investigated. Furthermore, a HPLC method was developed to accurately determine the content of unadsorbed HS-DOX in AuNPs-mPEG@DOX. The specificity, linearity, precision, stability and average recovery of this method were thoroughly investigated. The cytotoxic effect of AuNPs-mPEG@DOX on MCF-10A and MCF-7 cells was evaluated using a CCK-8 assay. Results AuNPs-mPEG@DOX was successfully prepared with Z-Average of (46.12±0.49) nm, Zeta potential of (18.60±1.51) nm and the maximum absorption wavelength of 530 nm. An efficient HPLC method for the detection of unadsorbed HS-DOX in AuNPs-mPEG@DOX was devised. The optimal dosage concentration of HS-DOX for AuNPs-mPEG@DOX was determined to be 11.18 μg/ml, resulting in a drug adsorption rate of (9.21±2.88)% and a drug loading rate of (2.01±0.62)%. Cytotoxicity experiments demonstrated that AuNPs-mPEG@DOX significantly reduced the toxic and side effects of DOX on normal breast cells. Additionally, AuNPs-mPEG@DOX and free DOX exhibited comparable cytotoxic effects on breast tumor cells when DOX concentration was equal to or greater than 4.75 μmol/L. Conclusion AuNPs-mPEG@DOX effectively reduce the toxicity of DOX, providing a reference for future research on reducing the toxicity of AuNPs-linked drugs.

Research progress on clinical application and quality control of sprays / 药学实践杂志

Sprays have gained significant attention and widespread use due to their numerous advantages, including rapid action, safety, and convenience. They are widely used in various fields such as dermatology, respiratory disease treatment, wound repair, and central nervous system targeted drug delivery. With the in-depth research of new drugs and modern pharmaceutics, the development ideas of sprays are more diverse, and the application scenarios are increasingly extensive. In this review the clinical application status of sprays and the latest research progress were summarized. Then the quality control parameters were briefly introduced，which provided reference for the research and development of sprays.

Establishment of determination of tetrodotoxin sustained-release microspheres / 药学实践杂志

Objective To establish a detection method for the determination of tetrodotoxin (TTX) in sustained-release microspheres. Methods The HPLC separation of tetrodotoxin was performed on an Agilent ZORBAX SB-C18 column (4.6mm×150mm,5 μm) with acetonitrile, 8mmol/L sodium heptane sulfonate containing 0.005% TFA (5:95) (pH 4.0) as the mobile phase. The flow rate was 1.0 ml/min. The UV detection wavelength was 200 nm and the column temperature was 30 °C. Results The method had good specificity and linearity of TTX in the concentration range of 1−20 μg/ml. The intra-day precision, inter-day precision, stability and repeatability of the method were good, and the average recoveries were found between 98.0% and 102.0%. Conclusion This study established an HPLC method which was suitable for the determination of tetrodotoxin sustained-release microspheres. The method is accurate and reliable within the applicable range, with strong specificity, which could lead to quantitative detection.

Construction and validation of an early predictive model for intraoperative massive transfusion of red blood cells in patients with Stanford type A aortic coarctation / 中国输血杂志

【Objective】 To analyze the risk factors for intraoperative massive red blood cell (RBC) transfusion in patients with Stanford type A aortic dissection (TAAD), in order to develop a risk-prediction model and validate its predictive effect. 【Methods】 The clinical data of 233 patients with TAAD admitted to our hospital from July 2018 to June 2021 (modeling set) were retrospectively analyzed. They were divided into routine transfusion group (n=128, RBC≤8 U) and massive transfusion group (n=105, RBC>8 U). Risk factors for intraoperative massive RBC transfusion in TAAD patients were analyzed by multivariate logistic regression and a risk prediction model was developed. Calibration curve and receiver operating characteristic (ROC) curve were used to assess the accuracy and discrimination of the model. In addition, 61 TAAD patients admitted to our hospital from July 2021 to May 2022 (validation set) were used for external validation. 【Results】 The rate of intraoperative massive RBC transfusion in 233 TAAD patients was 45.06% (95% CI: 38.59%-51.69%). Logistic analysis showed that women, age >50 years, preoperative Hb≤131.50 g/L, intraoperative bleeding >720 mL, and CPB time >155 min were independent risk factors for massive intraoperative RBC transfusion (P<0.05). The intraoperative risk prediction model formula for massive RBC infusion was: -4.427+ 0.925×gender+ 1.461×age+ 2.081×preoperative Hb+ 1.573×bleeding volume+ 2.823×CPB time. The area under the ROC curve of the modeling set and validation set were 0.904 (95% CI: 0.865-0.943) vs 0.868 (95%CI: 0.779-0.958), and the slopes of the calibration curves all converged to 1, indicating that the model predicted the risk of intraoperative massive RBC infusion in TAAD patients in good consistency with the actual risk of massive infusion. The decision curve shows that the model exhibits a positive net benefit with a threshold probability of 0.15-0.67 and has a high clinical application value. 【Conclusion】 The prediction model constructed based on the risk factors of intraoperative massive RBC infusion in TAAD patients can effectively predict the risk of intraoperative massive RBC infusion with high clinical predictive efficacy.

Advances in medicinal research on tetrodotoxin / 药学实践杂志

Tetrodotoxin (TTX) is a neurotoxin found in puffer fish and other marine organisms. It has been used as an inhibitor of voltage-gated sodium channels (VGSCs), which could selectively bind to the α-subunit on the outer vestibule of VGSCs, preventing sodium ions from entering the channel, resulting in pharmacological activities. As a typical sodium channel blocker, TTX shows a significant analgesic effect. TTX could selectively block Na+ channels without affecting other ion channels, therefore it could reduce the probability of adverse reactions caused by commonly used antiarrhythmic drugs. In addition, TTX has a significant role in detoxification and prevention of renal failure, so TTX has great potential as a medicine. The structure and physicochemical properties, mechanism of action, pharmacological activities and preparations of tetrodotoxin have been reviewed in this paper, so as to provide a general support for the evaluation of its druggability and application in the field of pharmacy.

Effects of tumor necrosis factor-alpha/extracellular signal-regulated kinase pathway on migration ability of HaCaT cells and full-thickness skin defects in mice / 中华烧伤杂志

Objective: To investigate the effects of tumor necrosis factor-alpha (TNF-α)/extracellular signal-regulated kinase (ERK) pathway on the migration ability of HaCaT cells and full-thickness skin defects in mice. Methods: The experimental research method was adopted. According to the random number table (the same below), HaCaT cells were divided into the normal oxygen group and the hypoxia group cultured under hypoxia (with oxygen volume fraction of 1%, the same below) condition. After 24 hours of culture, the significantly differentially expressed genes between the 2 groups were screened using the microarray confidence analysis software SAM4.01. The significance of the number of each gene in the signaling pathway was analyzed through the Kyoto encyclopedia of genes and genomes to screen the significantly differentially signaling pathways (n=3). HaCaT cells were cultured for 0 (immediately), 3, 6, 12, and 24 h under hypoxia condition. The secretion level of TNF-α was detected by enzyme-linked immunosorbent assay (ELISA), and the number of samples was 5. HaCaT cells were divided into normal oxygen group, hypoxia alone group, and hypoxia+inhibitor group cultured with FR180204 (an ERK inhibitor) and under hypoxia condition. The cells were cultured for 3, 6, 12, and 24 h. The migration ability of the cells was detected by scratch test (n=12). The expressions of phosphorylated nuclear factor kappa B (p-NF-κB), phosphorylated p38 (p-p38), phosphorylated ERK1/2 (p-ERK1/2), N-cadherin, and E-cadherin in HaCaT cells were detected by Western blotting under hypoxic condition for 0, 3, 6, 12, and 24 h (n=3). Sixty-four BALB/c male mice aged 6 to 8 weeks were used to make a full-thickness skin defect wound model on the dorsum of the mice. The mice were divided into the blank control group and the inhibitor group treated with FR180204, with 32 mice in each group being treated accordingly. On post injury day (PID) 0, 3, 6, 9, 12, and 15, the wound conditions of mice were observed and the healing rate was calculated (n=8). On PID 1, 3, 6, and 15, hematoxylin-eosin staining was used to observe neovascularization, inflammatory cell infiltration, and epidermal regeneration on wound, Masson staining was used to observe collagen deposition on wound, the expressions of p-NF-κB, p-p38, p-ERK12, N-cadherin, and E-cadherin in wound tissue were detected by Western blotting (n=6), the number of Ki67 positive cells and the absorbance value of vascular endothelial growth factor (VEGF) were detected by immunohistochemistry (n=5), the protein expressions of interleukin 6 (IL-6), IL-10, IL-1β, and CCL20 in wound tissue were detected by ELISA (n=6). Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, factorial design analysis of variance, Tukey test, least significant difference test, and independent sample t test. Results: After 24 hours of culture, compared with normal oxygen group, 7 667 genes were up-regulated and 7 174 genes were down-regulated in cells in hypoxic group. Among the above differentially expressed genes, the TNF-α signaling pathway had significant change (P<0.05) with large number of genes. Under hypoxia condition, the expression of TNF-α at 24 h of cell culture was (11.1±2.1) pg/mL, which was significantly higher than (1.9±0.3) pg/mL at 0 h (P<0.05). Compared with normal oxygen group, the migration ability of cells in hypoxia alone group was significantly enhanced at 6, 12, and 24 h of cell culture (with t values of 2.27, 4.65, and 4.67, respectively, P<0.05). Compared with hypoxia alone group, the migration ability of cells in hypoxia+inhibitor group was significantly decreased at 3, 6, 12, and 24 h of cell culture (with t values of 2.43, 3.06, 4.62, and 8.14, respectively, P<0.05). Under hypoxia condition, the expressions of p-NF-κB, p-ERK1/2, and N-cadherin were increased significantly at 12 and 24 h of cell culture compared with 0 h of culture (P<0.05), the expression of p-p38 was significantly increased at 3, 6, 12, and 24 h of cell culture (P<0.05), the expression of E-cadherin was significantly decreased at 6, 12, and 24 h of cell culture (P<0.05), the expression of p-ERK1/2, p-NF-κB, and E-cadherin was time-dependent. Compared with blank control group, on PID 3, 6, 9, 12, and 15, the wound healing rate of mice in inhibitor group was significantly decreased (P<0.05); there were more inflammatory cell infiltration around the wound edge of mice in inhibitor group on PID 3, 6, and 15, especially on PID 15, a large number of tissue necrosis and discontinuous new epidermal layer were observed on the wound surface, and collagen synthesis and new blood vessels were reduced; the expression of p-NF-κB in the wound of mice in inhibitor group was significantly decreased on PID 3 and 6 (with t values of 3.26 and 4.26, respectively, P<0.05) but significantly increased on PID 15 (t=3.25, P<0.05), the expressions of p-p38 and N-cadherin were significantly decreased on PID 1, 3, and 6 (with t values of 4.89, 2.98, 3.98, 9.51, 11.69, and 4.10, respectively, P<0.05), the expression of p-ERK1/2 was significantly decreased on PID 1, 3, 6, and 15 (with t values of 26.69, 3.63, 5.12, and 5.14, respectively, P<0.05), the expression of E-cadherin was significantly decreased on PID 1 (t=20.67, P<0.05) but significantly increased on PID 6 (t=2.90, P<0.05); the number of Ki67 positive cells and absorbance value of VEGF of wound in inhibitor group were significantly decreased on PID 3, 6, and 15 (with t values of 4.20, 7.35, 3.34, 4.14, 3.20, and 3.73, respectively, P<0.05); the expression of IL-10 in the wound tissue of the inhibitor group was significantly decreased on PID 6 (t=2.92, P<0.05), the expression of IL-6 was significantly increased on PID 6 (t=2.73, P<0.05), the expression of IL-1β was significantly increased on PID 15 (t=3.46, P<0.05), and CCL20 expression levels were significantly decreased on PID 1 and 6 (with t values of 3.96 and 2.63, respectively, P<0.05) but significantly increased on PID 15 (t=3.68, P<0.05). Conclusions: The TNF-α/ERK pathway can promote the migration of HaCaT cells, and regulate the healing of full-thickness skin defect wounds in mice by affecting the expression of inflammatory cytokines and chemokines.

Prevention and treatment of lung cancer by regulating tumor-associated macrophages with traditional Chinese medicine / 中国中药杂志

Lung cancer is one of the common malignant tumors in the world, and its incidence and mortality is increasing year by year. Interactions between tumor cells and immune cells in the tumor microenvironment(TME) affect tumor proliferation, infiltration, and metastasis. Tumor-associated macrophages(TAMs) are prominent components of TME, and they have dual regulation effects on malignant progression of lung cancer. The number, activity, and function of M2 macrophages are related to the poor prognosis of lung cancer, and M2 macrophages participate in tumor angiogenesis and immune escape. It has been proved that traditional Chinese medicines(TCMs) and their active ingredients can enhance the antitumor effects, reduce the toxicity of chemotherapy and radiotherapy, and prolong the survival rates of patients with cancer. This paper summarized the role of TAMs in the lung cancer initiation and progression, explored the molecular mechanism of TCM in regulating the recruitment, polarization phenotype, activity, and expression of related factors and proteins of TAMs, and discussed related signal pathways in the prevention and treatment of lung cancer based on the TCM theory of "reinforcing healthy qi and eliminating pathogen". This paper is expected to provide new ideas for the immunotherapy of targeted TAMs.

Research progress in control strategies of biological clock disorder / 生理学报

Circadian clock is an internal mechanism evolved to adapt to cyclic environmental changes, especially diurnal changes. Keeping the internal clock in synchronization with the external clock is essential for health. Mismatch of the clocks due to phase shift or disruption of molecular clocks may lead to circadian disorders, including abnormal sleep-wake cycles, as well as disrupted rhythms in hormone secretion, blood pressure, heart rate, body temperature, etc. Long-term circadian disorders are risk factors for various common critical diseases such as metabolic diseases, cardiovascular diseases, and tumor. To prevent or treat the circadian disorders, scientists have conducted extensive research on the function of circadian clocks and their roles in the development of diseases, and screened hundreds of thousands of compounds to find candidates to regulate circadian rhythms. In addition, melatonin, light therapy, exercise therapy, timing and composition of food also play a certain role in relieving associated symptoms. Here, we summarized the progress of both drug- and non-drug-based approaches to prevent and treat circadian clock disorders.

Machine and deep learning-based clinical characteristics and laboratory markers for the prediction of sarcopenia / 中华医学杂志(英文版)

BACKGROUND@#Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts.@*METHODS@#We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models.@*RESULTS@#The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC =0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), RF (AUC = 0.843, ACC = 0.836), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749).@*CONCLUSIONS@#The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR 1800018895.

Prognostic value of perioperative change of neutrophil elastase and myeloperoxidase in coronary circulation on perioperative myocardial injury and clinical outcome of patients underwent surgical valve replacement / 中华心血管病杂志

Objective: To investigate the clinical value of observing perioperative changes of myeloperoxidase (MPO) and neutrophil elastase (NE) in coronary artery circulation in patients underwent valve replacement surgery. Methods: This perspective cohort study was performed in patients who underwent valvular surgery in Nanjing Drum Tower Hospital and Fuwai Hospital from June 2021 to June 2022. Patients were divided into perioperative myocardial injury group and age-, sex- and type of cardiac procedure-matched non-perioperative myocardial injury control group in the ratio of 1∶1. Perioperative myocardial injury was defined as cardiac troponin T (cTnT)>0.8 μg/L on the first postoperative day (POD), and the cTnT level on the second POD increased by more than 10% compared with the cTnT level on the first POD. During the operation, blood samples were collected from the coronary sinus before clamping ascending aorta, and within 5 minutes after de-clamping ascending aorta. Then, the levels of MPO and NE on coronary sinus were continuously measured. The death, severe ventricular arrhythmia, pneumonia, re-intubation, repeat cardiac surgery, extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), continuous renal replacement therapy (CRRT), mechanical ventilation time and the duration of intensive care unit (ICU) were recorded. The levels of MPO and NE and the incidence of clinical outcomes were compared between the myocardial injury group and the control group. The independent risk factors of myocardial injury were analyzed by multivariate logistic regression. Results: A total of 130 patients were enrolled, aged (60.6±7.6) years old, with 59 males (45.4%). There were 65 patients in the myocardial injury group and 65 patients in the control group. During hospitalization, there was no death, ECMO, IABP and CRRT cases in both groups. Compared with the control group, the incidence of severe ventricular arrhythmia (13.8%(9/65) vs. 3.1%(2/65), P=0.03), pneumonia (20.0%(13/65) vs. 3.1%(2/65), P=0.03), re-intubation (6.2%(4/65) vs. 0, P=0.04) was significantly higher in myocardial injury group. The mechanical ventilation time (16.8(10.7, 101.7) h vs. 7.5(4.7, 15.1) h, P<0.01), and the duration of ICU (3.7(2.7, 18.9) vs. 2.7(1.8, 6.9)d, P<0.01) were significantly longer in myocardial injury group compared with the control group. There was no significant difference in the levels of MPO and NE in coronary sinus blood between the two groups before aortic clamping (all P>0.05). However, MPO ((551.3±124.2) μg/L vs. (447.2±135.9) μg/L, P<0.01) and NE ((417.0±83.1)μg/L vs. (341.0±68.3)μg/L, P<0.01) after 5 min aortic de-clamping were significantly higher in myocardial injury group than in the control group. Multivariate logistic regression analysis showed that the levels of NE (OR=1.02, 95%CI: 1.01-1.02, P<0.01), MPO (OR=1.00, 95%CI: 1.00-1.01, P=0.02) and mechanical ventilation time (OR=1.03, 95%CI: 1.01-1.06, P=0.02) were independent risk factors of myocardial injury in patients after surgical valvular replacement. Conclusion: Perioperative myocardial injury is related poor clinical outcomes, perioperative NE and MPO in coronary artery circulation are independent risk factors of perioperative myocardial injury in patients undergoing valve replacement surgery.

Clinical significance of early troponin I levels on the prognosis of patients with severe heat stroke / 中华危重病急救医学

OBJECTIVE@#To investigate the clinical significance of early troponin I (TnI) level in the prognosis of severe heat stroke.@*METHODS@#Clinical data of 131 patients with severe heat stroke in the intensive care unit (ICU) of the Affiliated Changzhou NO.2 People's Hospital of Nanjing Medical University (study dataset) and ICU 67 patients with severe heat stroke in Jintan First People's Hospital of Changzhou (validation dataset) were retrospectively analyzed from June 2013 to September 2022. The patients were divided into survival group and death group according to 30-day outcomes. TnI was collected within 24 hours after admission to the emergency department. Cox regression analysis was performed to analyze the risk factors of severe heat stroke death. Spearman correlation test was used to analyze the correlation between TnI and heart rate, and peripheral systolic blood pressure. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of TnI for death in patients with severe heat stroke. Decision curve analysis (DCA) was conducted to assess the clinical net benefit rate of TnI prediction. Grouping by TnI cut-off value, Kaplan-Meier survival curve was used to analyze 30-day cumulative survival. Sensitivity analysis included modified Possion regression, E-value, and subgroup forest map was used to evaluate the mortality risk of TnI in different populations. External dataset was used to verify the predictive value of TnI.@*RESULTS@#The death group had significantly higher TnI compared to the survival group [μg/L: 0.623 (0.196, 1.510) vs. 0.084 (0.019, 0.285), P < 0.01]. Multivariate Cox regression analysis after adjusting for confounding factors showed that TnI was an independent risk factor for death [hazard ratio (HR) = 1.885, 95% confidence interval (95%CI) was 1.528-2.325,P < 0.001]. Spearman correlation test showed that TnI was positively correlated with heart rate (r = 0.537, P < 0.001) and negatively correlated with peripheral systolic blood pressure (r = -0.611, P < 0.001). ROC curve showed that the area under the curve (AUC) of the TnI (0.817) was better than that of the acute physiology and chronic health evaluation II (APACHE II, 0.756). The DCA curve showed that the range of clinical net benefit rate of TnI (6.21%-20.00%) was higher than that of APACHE II score (5.14%-20.00%). Kaplan-Meier survival curve showed that patients in the low-risk group (TnI ≤ 0.106) had a significantly higher 30-day survival rate than that in the high-risk group (TnI > 0.106) group (Log-Rank test: χ2 = 17.350, P < 0.001). Modified Possion regression with adjustment for confounding factors showed that TnI was still an independent risk factor for death in patients with severe heat stroke [relative risk (RR) = 1.425, 95%CI was 1.284-1.583, P < 0.001]. The E-value was 2.215. The subgroup forest plot showed that the risk factors of TnI were obvious in male patients and patients ≤ 60 years old (male: HR = 1.731, 95%CI was 1.402-2.138, P < 0.001; ≤ 60 years old: HR = 1.651, 95%CI was 1.362-2.012, P < 0.001). In the validation dataset, ROC curve analysis showed that the AUC (0.836) of TnI predicting the prognosis of severe heat stroke was still higher than the APACHE II score (0.763).@*CONCLUSIONS@#Early elevation of TnI is a high-risk factor for death in patients with severe heat stroke, and it has a good predictive value for death.

Urine IL-6, IL-8, IL-33 and MMP-9 levels in patients with IgA nephropathy and their predictive value for disease progression / 中国医师杂志

Objective:To investigate the urineinterleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-33 (IL-33) and matrix metalloproteinase-9 (MMP-9) in patients with IgA nephropathy (IgAN) and their predictive value for disease progression.Methods:110 IgAN patients admitted to Zhuozhou Hospital from January 2018 to October 2021 were selected and divided into IgAN progression group (39 cases) and IgAN non progression group (71 cases) according to the progress of IgAN patients. According to the Oxford Classification Standard System (MEST-C) of IgAN, they were divided into MEST-C≥3 group (42 cases) and MEST-C<3 group (68 cases). According to the estimated glomerular filtration rate (eGFR), they were divided into eGFR≥50 ml/(min·1.73 m 2) group (group A, 63 cases) and eGFR<50 ml/(min·1.73 m 2) group (group B, 47 cases). According to the amount of urinary protein, they were divided into urinary protein≥1.5 g/24 h group (66 cases) and urinary protein<1.5 g/24 h group (44 cases). Multivariate logistic regression was used to analyze the risk factors affecting the progression of IgAN. Receiver operating characteristic (ROC) curve was drawn to analyze the value of urinary IL-6, IL-8, IL-33 and MMP-9 levels in predicting the progression of IgAN. Results:The urinary IL-6, IL-8, IL-33 and MMP-9 levels in IgAN progression group were significantly higher than those in IgAN non progression group, while the serum albumin, eGFR and complement C3 in the IgAN progression group were lower than those in the IgAN non progression group (all P<0.05). The urinary IL-6, IL-8, IL-33 and MMP-9 levels in the MEST-C≥3 group were significantly higher than those in the MEST-C<3 group (all P<0.001). The urinary IL-6, IL-8, IL-33 and MMP-9 levels in the eGFR<50 ml/(min·1.73 m 2) group were significantly higher than those in the eGFR≥50 ml/(min·1.73 m 2) group (all P<0.001). The urinary IL-6, IL-8, IL-33 and MMP-9 in the urinary protein≥1.5 g/24 h group were significantly higher than those in the urinary protein<1.5 g/24 h group (all P<0.001). Multivariate logistic regression analysis showed that the course of disease, serum albumin, eGFR, urinary protein, IL-6, IL-8, IL-33 and MMP-9 were risk factors affecting the progression of IgAN (all P<0.005). The ROC curve showed that the area under the curve (AUC) of IL-6, IL-8, IL-33 and MMP-9 in predicting the progression of IgAN was 0.956 (95% CI: 0.891-0.998), and the sensitivity and specificity were 98.4% and 86.2%, respectively. Conclusions:The elevated levels of urinary IL-6, IL-8, IL-33 and MMP-9 are closely related to the progress of IgAN, and the combination of these four indicators has a good value in predicting the progress of IgAN.

Analysis of drug therapy in a patient with pulmonary infection secondary to suppurative thrombophlebitis / 药学实践杂志

Objective To explore the role of pharmaceutical care in the treatment of patients with pulmonary infection secondary to suppurative thrombophlebitis. Methods The treatment of a patient diagnosed with pulmonary metastatic infection secondary to suppurative thrombophlebitis and the whole process of clinical pharmacists participating in the monitoring were analyzed retrospectively. The use of antibiotics was evaluated, and the experience of coagulation management in suppurative thrombophlebitis was explored. Results Based on the infection site, characteristics of septic thrombus, monitoring of vancomycin blood concentration, pharmacokinetics and pharmacodynamics characteristics of antibiotics, clinical pharmacists provided comprehensive pharmaceutical services for clinicians and patients in terms of anti-infection scheme adjustment, optimization of vancomycin individualized treatment, anticoagulant timing. Patient’s systemic infection and septic thrombus can be effectively controlled and which promotes the treatment of patients with suppurative thrombophlebitis. Conclusion Clinical pharmacists can play an important role in the treatment team of severe patients to improve the rational use of antibiotics.

A Nomogram model involving preoperative inflammatory markers for predicting postoperative overall survival in patients with stage Ⅰ-Ⅲ gastric cancer / 中华普通外科杂志

Objective:To establish a nomogram to predict overall survival of patients with stage Ⅰ-Ⅲ gastric cancer (GC) based on preoperative inflammatory markers.Methods:Clinicopathological and follow-up data of 1 035 patients with stage Ⅰ-Ⅲ gastric cancer operated at He'nan Cancer Hospital between May 2015 and Oct 2016 were retrospectively collected. A nomogram was established based on prognostic factors. Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to verify the performance of the model according to differentiation, calibration and clinical utility.Results:A total of 1 035 patients were enrolled . The median follow-up time was 41.9 months; According to the optimal cutoff value, 170 were with elevated neutrophil-to-lymphocyte ratio (NLR) and 865 with a reduced　ratio; 562 in elevated platelet-to-lymphocyte ratio (PLR) vs. 473 in the reduced group; fibrinogen/albumin ratio (FAR) elevated in 108 group vs. 972 in the reduced group; 180 in the prognostic nutritional index score (PNI) elevated group and 855 in the reduced group. Two hundred and sixty-seven patients were categorized at stage Ⅰ, 334 at stage Ⅱ ,434 at stage Ⅲ. Multivariate regression analysis showed tumor location, vascular tumor thrombus, pTNM stage, FAR, PNI and NLR were independent prognostic factors (all P<0.05). The C-index of the nomogram was 0.723 (95% CI: 0.710 -0.736) and had better clinical utility than the American Joint Committee on Cancer (AJCC) 8th TNM staging system 0.693 (95% CI, 0.681 -0.705). The calibration curve of the nomogram showed that the predicted survival rate was consistent with the actual survival rate in GC patients. Compared to AJCC 8th pTNM staging system, the DCA curve indicate that the nomogram has a higher net income. Conclusion:The nomogram predicting overall survival of patients with stage Ⅰ-Ⅲ gastric cancer is established and verified , which provides better individual prediction than TNM staging system.

Effect of the number of retrieval attempts on the outcomes after successful recanalization of mechanical thrombectomy in patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the effect of the number of retrieval attempts on the outcomes after successful recanalization of mechanical thrombectomy in patients with acute ischemic stroke.Methods:Patients with acute large vessel occlusive ischemic stroke underwent mechanical thrombectomy and successful postoperative recanalization in the Stroke Center of Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2019 to May 2020 were retrospectively enrolled. According to the number of retrieval attempts during the procedure, the patients were divided into <3-attempt group and ≥3-attempt group. The demographic data, procedure-related indexes, periprocedural complications and outcomes at 90 d after the procedure were compared between the two groups.Results:A total of 106 patients, aged 69.8±1.3 years, were enrolled, and 55 were males (51.9%). Eight-three patients (78.3%) were in the <3-attempt group, and 23 (21.7%) were in the ≥3-attempt group. Forty-one patients (38.7%) had good outcomes (the modified Rankin Scale score ≤2) at 90 d, and 11 (10.4%) died. There were no significant differences in the incidence of intracranial hemorrhage (30.4% vs. 20.5%; χ2=1.019, P=0.313), the good outcome rate at 90 d (34.8% vs. 39.8%; χ2=0.188, P=0.665) and mortality (8.7% vs. 10.8%; P=0.999) between the ≥3-attempt group and <3-attempt group, but the incidence of symptomatic intracranial hemorrhage was significantly higher than that in the <3-attampt group (13.0% vs. 1.2%; P=0.031). Multivariate logistic regression analysis showed that the number of retrieval attempts was not significantly associated with poor outcome. Conclusion:The more retrieval attempts may be related to symptomatic intracranial hemorrhage, but it does not affect the clinical outcomes of patients with successful recanalization at 3 months.