Design, synthesis and biological study of BTK/JAK3 dual-target inhibitors / 中国药科大学学报

@#Abstract: In the present study, the compound XL-12 from our previous work was utilized as a lead compound. Through the optimization of the terminal phenyl ring, 12 target compounds were designed and synthesized. The structures of all target compounds were confirmed by 1H NMR, 13C NMR, and H RMS. In vitro enzyme activity assay showed that most compounds demonstrated significant inhibitory activity toward Bruton’s tyrosine kinase (BTK) and Janus kinase 3 (JAK3). Among them, compound I-3 exhibited moderate cell proliferation inhibitory activity toward Daudi cells and BaF3-JAK3 cells. In the evaluation of anti-inflammatory activity in vitro, compound I-3 could effectively inhibit the production of inflammatory factors IL-6; besides, it exhibited superior anti-inflammatory activity compared to ibrutinib in xylene-induced ear swelling model in mice.

Efficacy of multidisciplinary team combined with Da Vinci robot-assisted thoracic surgery in the treatment of early non-small cell lung cancer: A retrospective study in a single center / 中国胸心血管外科临床杂志

@#Objective To investigate the clinical efficacy of multidisciplinary team (MDT) model combined with Da Vinci robot-assisted thoracic surgery in the treatment of early non-small cell lung cancer (NSCLC). Methods From July 2020 to December 2021, the patients with NSCLC who received Da Vinci robot-assisted thoracic surgery in the Department of Thoracic Surgery, General Hospital of Northern Theater Command were collected. According to whether MDT were performed before hospitalization, the patients were divided into an MDT group and a common group. The recovery and clinical efficacy were compared between the two groups. Results A total of 187 patients were enrolled, including 81 males and 106 females, aged 63 (56, 67) years. There were 85 patients in the MDT group, and 102 patients in the common group. Compared with the common group, the MDT group had lower incidence of postoperative complications (9.4% vs. 29.4%, P=0.017), shorter intraoperative operation time [55 (45, 61) min vs. 79 (65, 90) min, P<0.001], and less intraoperative blood loss [25 (20, 30) mL vs. 30 (20, 50) mL, P=0.029] in the same operation mode. In addition, the drainage volume on the second postoperative day [270 (200, 350) mL vs. 215 (190, 300) mL, P=0.004], the number of dissected lymph nodes groups [6 (5, 6) groups vs. 5 (3, 6) groups, P=0.004] and the number of dissected lymph nodes [16 (13, 21) vs. 13 (9, 20), P=0.005] in the MDT group were significantly better than those in the common group. The differences in the postoperative intubation time and postoperative hospital stay between the two groups were not statistically significant (P>0.05). Conclusion MDT combined with Da Vinci robot-assisted thoracic surgery can further reduce the risk of surgery, improve the clinical treatment effect, reduce the incidence of postoperative complications, and accelerate the rehabilitation of patients.

Application of digital drainage system after da Vinci robot-assisted lobectomy: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective To investigate the clinical effect of digital drainage system (DDS) in patients after robot-assisted lobectomy. Methods The clinical data of the patients who underwent da Vinci robot-assisted lobectomy from August 2020 to December 2021 were retrospectively analyzed. The patients were divided into a DDS group and a conventional group (using traditional single thoracic drainage tube device) according to different drainage devices used after operation. The preoperative data, intraoperative blood loss, total drainage volume within 48 h after operation, postoperative extubation time and postoperative hospital stay were compared between the two groups. Results Finally, 170 patients were collected, including 76 males and 94 females with an average age of 61.8±8.7 years. Postoperative extubation time [5.53 (6.00, 7.00) days vs. 6.36 (6.00, 8.00) days, Z=–2.467, P=0.014] and postoperative hospital stay [7.80 (8.00, 10.00) days vs. 8.94 (9.00, 10.00) days, Z=–2.364, P=0.018] in the DDS group were shorter than those in the conventional group. For patients with postoperative persistent air leak, postoperative extubation time (Z=–2.786, P=0.005) and postoperative hospital stay (Z=–2.862, P=0.003) in the DDS group were also shorter than those in the conventional group. Conclusion DDS has a positive effect on enhanced recovery after robot-assisted lobectomy, which is safe and stable, and is beneficial to postoperative rehabilitation and shortening the average hospital stay.

Study on learning curve of Da Vinci robotic segmentectomy / 中国胸心血管外科临床杂志

@#Objective To analyze the learning curve of Da Vinci robotic segmentectomy. Methods Cumulative sum analysis (CUSUM) was used to analyze the learning curve of Da Vinci robotic segmentectomy performed by the General Hospital of Northern Theater Command from February 2018 to December 2020. The learning curve was obtained by fitting, and R2 was used to judge the goodness of fitting. The clinical data of patients in different stages of learning curve were compared and analyzed. Results The first 50 patients who received Da Vinci robotic segmentectomy were included, including 24 males and 26 females, with an average age of 61.9±10.6 years. The operation time decreased gradually with the accumulation of operation patients. The goodness of fitting coefficient reached the maximum value when R2=0.907 (P<0.001), CUSUM (n) =0.009×n3−0.953×n2+24.968×n−7.033 (n was the number of patients). The fitting curve achieved vertex crossing when the number of patients reached 17. Based on this, 50 patients were divided into two stages: a learning and improving stage and a mastering stage. There were statistical differences in the operation time, intraoperative blood loss, postoperative drainage volume, number of lymph node dissection, postoperative catheter time, postoperative hospital stay, and postoperative complications between the two stages (P<0.05). Conclusion It shows that the technical competency for assuring feasible perioperative outcomes can be achieved when the cumulative number of surgical patients reaches 17.

Analysis and evaluation of bioactive constituents from different parts of Epimedium brevicornum / 中国中药杂志

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 μm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.

Construction and application value of CT based radiomics model in predicting the prognosis of patients with gastric neuroendocrine neoplasm / 中华消化外科杂志

Objective:To construct of a computed tomography (CT) based radiomics model for predicting the prognosis of patients with gastric neuroendocrine neoplasm (GNEN) and inves-tigate its application value.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 182 patients with GNEN who were admitted to 2 medical centers, including the First Affiliated Hospital of Zhengzhou University of 124 cases and the Affiliated Cancer Hospital of Zhengzhou University of 58 cases, from August 2011 to December 2020 were collected. There were 130 males and 52 females, aged 64(range, 56-70)years. Based on random number table, all 182 patients were divided into the training dataset of 128 cases and the validation dataset of 54 cases with a ratio of 7:3. All patients underwent enhanced CT examination. Observation indicators: (1) construction and validation of the radiomics prediction model; (2) analysis of prognostic factors for patients with GNEN in the training dataset; (3) construction and evaluation of the prediction model for prognosis of patients with GNEN. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and the chi-square test, corrected chi-square test or Fisher exact probability were used for comparison between groups. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX regression model was used for univariate and multivariate analyses. The R software (version 4.0.3) glmnet software package was used for least absolute shrinkage and selection operator (LASSO)-COX regression analysis. The rms software (version 4.0.3) was used to generate nomogram and calibration curve. The Hmisc software (version 4.0.3) was used to calculate C-index values. The dca.R software (version 4.0.3) was used for decision curve analysis. Results:(1) Construction and valida-tion of the radiomics prediction model. One thousand seven hundred and eighty-one radiomics features were finally extracted from the 182 patients. Based on the feature selection using intra-group correlation coefficient >0.75, and the reduce dimensionality using LASSO-COX regression analysis, 14 non zero coefficient radiomics features were finally selected from the 1 781 radiomics features. The radiomics prediction model was constructed based on the radiomics score (R-score) of these non zero coefficient radiomics features. According to the best cutoff value of the R-score as -0.494, 128 patients in the training dataset were divided into 64 cases with high risk and 64 cases with low risk, 54 patients in the validation dataset were divided into 35 cases with high risk and 19 cases with low risk. The area under curve (AUC) of radiomics prediction model in predicting 18-, 24-, 30-month overall survival rate of patients in the training dataset was 0.83[95% confidence interval ( CI ) as 0.76-0.87, P<0.05], 0.84(95% CI as 0.73-0.91, P<0.05), 0.91(95% CI as 0.78-0.95, P<0.05), respectively. The AUC of radiomics prediction model in predicting 18-, 24-, 30-month overall survival rate of patients in the validation dataset was 0.84(95% CI as 0.75-0.92, P<0.05), 0.84 (95% CI as 0.73-0.91, P<0.05), 0.86(95% CI as 0.82-0.94, P<0.05), respectively. (2) Analysis of prognostic factors for patients with GNEN in the training dataset. Results of multivariate analysis showed gender, age, treatment method, tumor boundary, tumor T staging, tumor N staging, tumor M staging, Ki-67 index, CD56 expression were independent factors influencing prognosis of patients with GNEN in the training dataset ( P<0.05). (3) Construction and evaluation of the prediction model for prognosis of patients with GNEN. The clinical prediction model was constructed based on the independent factors influen-cing prognosis of patients with GNEN including gender, age, treatment method, tumor boundary, tumor T staging, tumor N staging, tumor M staging, Ki-67 index, CD56 expression. The C-index value of clinical prediction model in the training dataset and the validation dataset was 0.86 (95% CI as 0.82-0.90) and 0.80(95% CI as 0.72-0.87), respectively. The C-index value of radiomics prediction model in the training dataset and the validation dataset was 0.80 (95% CI as 0.74-0.86, P<0.05) and 0.75(95% CI as 0.66-0.84, P<0.05), respectively. The C-index value of clinical-radiomics combined prediction model in the training dataset and the validation dataset was 0.88(95% CI as 0.85-0.92) and 0.83 (95% CI as 0.77-0.89), respectively. Results of calibration curve show that clinical prediction model, radiomics prediction model and clinical-radiomics combined prediction model had good predictive ability. Results of decision curve show that the clinical-radiomics combined prediction model is superior to the clinical prediction model, radiomics prediction model in evaluating the prognosis of patients with GNEN. Conclusions:The predection model for predicting the prognosis of patients with GNEN is constructed based on 14 radiomics features after selecting. The prediction model can predict the prognosis of patients with GNEN well, and the clinical-radiomics combined prediction model has a better prediction efficiency.

Preoperative prediction of vessel invasion in locally advanced gastric cancer based on venous phase enhanced CT radiomics and machine learning / 中华放射学杂志

Objective:To evaluate the value of preoperative prediction of vessel invasion (VI) of locally advanced gastric cancer by machine learning model based on the venous phase enhanced CT radiomics features.Methods:A retrospective analysis of 296 patients with locally advanced gastric cancer confirmed by pathology in the First Affiliated Hospital of Zhengzhou University from July 2011 to December 2020 was performed. The patients were divided into VI positive group ( n=213) and VI negative group ( n=83) based on pathological results. The data were divided into training set ( n=207) and test set ( n=89) according to the ratio of 7∶3 with stratification sampling. The clinical characteristics of patients were recorded, and the independent risk factors of gastric cancer VI were screened by multivariate logistic regression. Pyradiomics software was used to extract radiomic features from the venous phase enhanced CT images, and the minimum absolute shrinkage and selection algorithm (LASSO) was used to screen the features, obtain the optimal feature subset, and establish the radiomics signature. Four machine learning algorithms, including extreme gradient boosting (XGBoost), logistic, naive Bayes (GNB), and support vector machine (SVM) models, were used to build prediction models for the radiomics signature and the screened clinical independent risk factors. The efficacy of the model in predicting gastric cancer VI was evaluated by the receiver operating characteristic curve. Results:The degree of differentiation (OR=13.651, 95%CI 7.265-25.650, P=0.003), Lauren′s classification (OR=1.349, 95%CI 1.011-1.799, P=0.042) and CA199 (OR=1.796, 95%CI 1.406-2.186, P=0.044) were independent risk factors for predicting the VI of locally advanced gastric cancer. Based on the venous phase enhanced CT images, 864 quantitative features were extracted, and 18 best constructed radiomics signature were selected by LASSO. In the training set, the area under the curve (AUC) of XGBoost, logistic, GNB and SVM models for predicting gastric cancer VI were 0.914 (95%CI 0.875-0.953), 0.897 (95%CI 0.853-0.940), 0.880 (95%CI 0.832-0.928) and 0.814 (95%CI 0.755-0.873), respectively, and in the test set were 0.870 (95%CI 0.769-0.971), 0.877 (95%CI 0.788-0.964), 0.859 (95%CI 0.755-0.961) and 0.773 (95%CI 0.647-0.898). The logistic model had the largest AUC in the test set. Conclusions:The machine learning model based on the venous phase enhanced CT radiomics features has high efficacy in predicting the VI of locally advanced gastric cancer before the operation, and the logistic model demonstrates the best diagnostic efficacy.

A New Calculation Model for Calcium Requirements After Parathyroidectomy in Patients With Secondary Hyperparathyroidism

Objectives@#. We aimed to develop a new calculation model for calcium requirements in dialysis patients following parathyroidectomy. @*Methods@#. A total of 98 patients with secondary hyperparathyroidism receiving parathyroidectomy from January 2014 to January 2022 were enrolled in this study. Among these patients, 78 were randomly selected for construction of the calcium requirement calculation model, and the remaining 20 patients were selected for model validation. The calcium requirement model estimated the total calcium supplementation for 1 week after surgery using variables with significant relationships in the derivation group by stepwise multiple linear regression analysis. Bias, precision, and accuracy were measured in the validation group to determine the performance of the model. @*Results@#. The model was as follows: calcium requirement for 1 week after surgery=33.798–8.929×immediate postoperative calcium+0.190×C-reactive protein–0.125×age+0.002×preoperative intact parathyroid hormone+0.003×preoperative alkaline phosphatase (R2=0.8). The model was successfully validated. @*Conclusion@#. We generated a novel model to guide calcium supplementation. This model can assist in stabilizing the serum calcium levels of patients during the early postoperative period. Furthermore, it contributes to the individualized and precise treatment of hypocalcemia in patients following parathyroidectomy.

Perioperative outcomes of robot-assisted versus video-assisted left upper lobectomy in non-small cell lung cancer: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective    To summarize the efficacy of robot-assisted thoracic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) in the treatment of left upper lobectomy for non-small cell lung cancer. Methods    The clinical data of patients with non-small cell lung cancer who underwent left upper lobectomy with RATS or VATS in our center from January 2019 to October 2021 were retrospectively analyzed. The patients were divided into two groups according to surgical methods: a RATS group and a VATS group. The baseline clinical data and results were compared between the two groups. Results    A total of 145 patients were included. There were 78 males and 67 females with a mean age of 59.9 years. There were 63 patients in the RATS group and 82 patients in the VATS group. There was no death within 30 days after operation in both groups. In the RATS group, the drainage volume on the second postoperative day (233.49±83.94 mL vs. 284.88±120.21 mL, P=0.003), total operative time (126.94±29.50 min vs. 181.59±61.51 min, P=0.000), intraoperative resection time of the left upper lobe (76.48±27.52 min vs. 107.23±47.84 min, P=0.000), intraoperative blood loss (P=0.000), and conversion rate to thoracotomy (P=0.018) were significantly better than those in the VATS group. The group (5.41±0.94 groups vs. 4.83±1.31 groups, P=0.002) and number (18.27±7.39 vs. 12.76±6.54, P=0.000) of dissected lymph nodes in the RATS group were significantly more than those in the VATS group. The differences in the drainage volume on the first day after operation, postoperative intubation time, postoperative hospital stay or postoperative complications between the two groups were not statistically significant (P>0.05). Conclusion    The application of RATS in the left upper lobectomy for non-small cell lung cancer is safe and feasible, and has obvious advantages over VATS.

Perioperative effects of da Vinci robot with totally no tube versus subxiphoid video-assisted thymectomy surgery for thymic tumors: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective     To compare the clinical efficacy and safety of da Vinci robot with totally no tube (TNT) versus subxiphoid video-assisted thymectomy surgery (SVATS) in the treatment of thymic tumors. Methods     From 2019 to 2021, a retrospective analysis was conducted on patients with thymic tumor resection in the Department of Thoracic Surgery, General Hospital of Northern Theater Command. All patients underwent total thymectomy and mediastinal fat removal, and they were divided into a TNT group and a SVATS group according to the operation method. The intraoperative blood loss, conversion rate, postoperative visual analogue score (VAS), postoperative hospital stay time and postoperative complications were compared between the two groups. Results     We finally included 435 patiets. There were 168 patients with 83 males and 85 females at an average age of 61.920±9.210 years in the TNT group and 267 patients with 147 males and 120 females at an average age of 61.460±8.119 years in the SVATS group. There was no death or postoperative myasthenic crisis in both groups. There was no statistical difference in postoperative hospital stay (1.540±0.500 d vs. 3.400±0.561 d, P=0.000), intraoperative blood loss (13.450±5.498 mL vs. 108.610±54.462 mL, P=0.000), postoperative 24 h VAS score (4.960±1.757 points vs. 3.600±1.708 points, P=0.000), or postoperative complication rate (3.0% vs. 11.6%, P=0.001). Conclusion     TNT is a more efficient, safe, and effective surgical approach for treating thymic tumors, which can shorten hospital stay time and reduce postoperative complications. However, SVATS can minimize postoperative pain.

Heixiaoyao Powder interferes with microglia polarization in AD model mice by regulating NOX2/ROS/NF-κB signaling pathway / 中国中药杂志

The effect and mechanism of Heixiaoyao Powder on the polarization of microglia(MG) in APP/PS1 double transgenic mice were explored based on NADPH oxidase 2(NOX2)/reactive oxygen species(ROS)/nuclear factor kappaB(NF-κB) signaling pathway. Fifty 4-month-old male APP/PS1 mice were randomly divided into a model group, an MCC950 group(10 mg·kg~(-1)), and low-, medium-, and high-dose Heixiaoyao Powder groups(6.45, 12.89, and 25.78 g·kg~(-1)). Thirty male C57BL/6J mice of the same age and strain were randomly divided into a blank group, a blank + intragastric intervention group, and a blank + intraperitoneal injection group. Drug intervention lasted 90 days. Morris water maze test was used to detect learning and cognitive ability. Nissl staining and transmission electron microscopy were used to observe the pathological morphology and ultrastructure of hippocampal neurons. Immunofluorescence was used to detect the positive expression of M1-type marker CD16/32~+/Iba-1~+, M2-type marker CD206~+/Iba-1~+ of MG and the expression of hippocampal ROS. The colorimetric method was used to detect the content of malondialdehyde(MDA) and superoxide dismutase(SOD) in the hippocampus. Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory factors, including interleukin-6(IL-6), interleukin-8(IL-8), and tumor necrosis factor-α(TNF-α), in the hippocampus. Western blot was used to detect the protein expression of β-amyloid protein(Aβ), Iba-1, CD16/32, CD206, NOX2, NF-κB, p-NF-κB, NF-κB inhibitor alpha(IκBα), and p-IKBα in the hippocampus. The results showed that as compared with the blank group, the model group showed prolonged target quadrant movement distance and escape latency(P<0.01), shortened target quadrant retention time and percentage(P<0.01), disorganized neuronal cells with swelling, nuclear disappearance or bias, reduced number of cells, dissolved or absent Nissl bodies, and a clear area in the cytoplasm, damaged and shrunk cell membrane with abnormal cell morphology, few organelles in the cytoplasm, reduced and swollen mitochondria, increased MG M1-type marker CD16/32~+/Iba-1~+(P<0.01), decreased M2-type marker CD206~+/Iba-1~+(P<0.01), increased ROS activity and MDA content(P<0.01), decreased SOD level(P<0.01), elevated inflammatory factors IL-6, IL-8, and TNF-α(P<0.01), up-regulated protein expression and phosphorylation of Aβ, CD16/32, Iba-1, NOX2, NF-κB, and IKBα(P<0.01), and down-regulated CD206(P<0.01). There was no statistically significant difference between the blank group, the blank + intragastric intervention group, and the blank + intraperitoneal injection group. After the intervention of Heixiaoyao Powder, the Heixiaoyao Powder groups showed shortened target quadrant movement distance and escape latency(P<0.01), prolonged target quadrant retention time and percentage(P<0.01), increased and neatly arranged cells with relieved swelling, increased Nissl bodies, regular cell morphology, and intact cell membrane, relieved swelling of mitochondria, slightly expanded endoplasmic reticulum, decreased CD16/32~+/Iba-1~+(P<0.05 or P<0.01), increased CD206~+/Iba-1~+(P<0.01), decreased ROS activity and MDA content(P<0.01), increased SOD level(P<0.01), decreased content of inflammatory factors IL-6, IL-8, and TNF-α(P<0.01), down-regulated protein expression and phosphorylation of Aβ, CD16/32, Iba-1, NOX2, NF-κB, and IKBα(P<0.01), and up-regulated CD206(P<0.01). In conclusion, Heixiaoyao Powder can alleviate neuronal damage and improve the learning and memory abilities of APP/PS1 mice. The mechanism of action may be related to the inhibition of NOX2/ROS/NF-κB signaling pathway, regulating the polarization of MG, increasing the expression of M2 type, inhibiting the expression of M1 type, and reducing the release of inflammatory factor.

Quality evaluation of Lysimachiae Herba from different habitats based on simultaneous determination of multiple bioactive constituents combined with multivariate statistical analysis / 中国中药杂志

A method based on ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap-tandem mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 41 bioactive constituents of flavonoids, organic acids, nucleosides, and amino acids in Lysimachiae Herba. The content of multiple bioactive constituents was compared among the samples from different habitats. The chromatographic separation was performed in a Waters XBridge®C_(18) column(4.6 mm×100 mm, 3.5 μm) at 30 ℃. The gradient elution was performed with 0.4% methanol(A)-formic acid water(B) as the mobile phase at a flow rate of 0.8 mL·min~(-1), and the multiple-reaction monitoring(MRM) mode was adopted. According to the content of 41 constituents, hierarchical cluster analysis(HCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and gray relational analysis(GRA) were perfomed to comprehensively evaluate the samples from different habitats. The results showed that the 41 constituents exhibited good linear relationship within the tested concentration ranges, with the correlation coefficients(r) greater than 0.999 4. The method featured good precision, repeatability, and stability with the relative standard deviations(RSDs) less than 5.0%. The average recoveries of the 41 constituents ranged from 98.06% to 101.9%, with the RSDs of 0.62%-4.6%. HCA and OPLS-DA separated 48 batches of Lysimachiae Herba samples from different habitats into three categories: the producing areas in Sichuan and Chongqing, the producing areas in Jiangsu, Zhejiang, and Jiangxi, and the producing areas in Guizhou. The content of 41 constituents varied among the Lysimachiae Herba samples from different habitats. The GRA results revealed that the Lysimachiae Herba sample from Nanchong City, Sichuan Province had the best comprehensive quality. The method developed in this study was accurate and reliable and thus can be used for comprehensive evaluation of Lysimachiae Herba quality and provide basic information for the selection of habitats.

Study on the relation of the radiochemical purity and in vivo imaging effect of 68Ga-DOTATATE injection / 中华核医学与分子影像杂志

Objective:To explore the relation of the radiochemical purity and in vivo imaging effect of 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)- D-phe1-Tyr3-Thr8-octreotide (TATE) injection. Methods:High performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) methods were established to determine 68Ga-DOTATATE, 68Ga 3+ , 68Ga in colloidal form and 68Ga-DOTA- D-Phe1-Tyr3-Thr8-dethreonine-octreotide (heptapeptide) and to study the influence of precursor purity on radiochemical purity of labelled products. The uptake of 68Ga-DOTATATE injection with different radiochemical purities was investigated in nude mice bearing AR42J cells by microPET imaging and the tumor target/non-target (T/NT) value was calculated. One-way analysis of variance and Pearson correlation analysis were used to analyze the data. Results:The contents of 68Ga 3+ and 68Ga in colloidal form were not related with precursor purity ( r values: 0.385, 0.497, P values: 0.306, 0.137), while the content of 68Ga-DOTA-heptapeptide was positively related with the purity of DOTA-heptapeptide ( r=0.957, P<0.001). The radiochemical purities of 68Ga-DOTATATE injection were (87.0±2.3)%, (86.8±0.8)% and (94.0±3.1)% when the DOTATATE purities were 90.9%, 91.6% and 99.2%, respectively. The results of microPET imaging showed that the tumor uptake was positively related with the radiochemical purity of 68Ga-DOTATATE injection ( r=0.828, P<0.001), and the T/NT values of 68Ga-DOTATATE injection with radiochemical purities of 95.7%, 85.8%, 84.5% and 79.9% were 21.25±8.84, 8.50±1.51, 11.38±1.65 and 6.01±0.99, respectively ( F=11.48, P=0.001). Conclusion:The radiochemical purity of 68Ga-DOTATATE injection is impacted by the purity of labelled precursor and manufacturing processes and is related with the imaging effect in vivo.

Clinical comprehensive evaluation of Reyanning Mixture in treatment of acute upper respiratory tract infection (heat-toxin attacking lung syndrome) / 中国中药杂志

This study systematically sorted out the evidence data of the safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine(TCM) of Reyanning Mixture in the treatment of acute upper respiratory tract infection(heat-toxin attacking lung syndrome) with the qualitative and quantitative evaluation methods adopted. Based on evidence-based medicine, epidemiology, clinical medicine, evidence-based pharmacy, pharmacoeconomics, and health technology evalua-tion(HTA), the clinical value of Reyanning Mixture was evaluated using multi-criteria decision analysis(MCDA) model, Chinese patent medicine clinical evidence, and value evaluation software(CSC v2.0). The SRS monitoring data, Meta-analysis, and other safety evidence showed that the main adverse reactions of Reyanning Mixture were nausea, diarrhea, and rash, and no serious adverse reactions were found. The pharmacovigilance system was sound, and the system was perfect. There was no recall, notification, or interview for unqualified products. Based on the existing research, the evidence was sufficient, and the risk was controllable. Hence, its safety was grade A. Meta-analysis showed that in the treatment of acute upper respiratory tract infection, Reyanning Mixture combined with Amoxicillin Capsules was better than Amoxicillin Capsules alone in shortening the complete fever relief time and improving the cure rate. Besides, it was superior to Shuanghuanglian Granules in shortening the complete fever relief time, cough relief time, nasal congestion relief time, and pharyngeal congestion relief time. The Meta-analysis was conducted based on AMSTAR standard, and its ove-rall quality was proved good. The evidence quality in GRADE system evaluation was medium and low. The quality of evidence was medium, and the clinical value was obvious. Hence, its effectiveness was grade A. The results of pharmacoeconomic research showed that compared with Amoxicillin Capsules, Reyanning Mixture alone or in combination with Amoxicillin Capsules had cost-effectiveness advantages in the treatment of acute upper respiratory tract infection, and the results were stable in sensitivity analysis. According to the CASP economic evaluation checklist, the research problems were clear and the results were reliable. As revealed by the comprehensive evaluation, the evidence quality was sufficient and the result was clear. Its economy was grade B. Reyanning Mixture had multiple therapeutic targets like anti-virus, anti-bacteria, antipyresis, and anti-cough, with good clinical innovation. There were many innovative initiatives in ensuring drug supply, especially at the grass roots, drug safety, and effectiveness, and also multiple innovative contributions to production technology, quality control, scientific and technological research and development, and enterprise management and marketing. Therefore, its innovation was grade B. The dosage form of Reyanning was mixture, which made it convenient for storage and transportation. The usage was easy to be mastered and accepted by doctors and nurses, exhibiting good suitability for clinicians, nurses, pharmacists, and patients who received this drug and basically meeting the needs of clinical medication. The suitability was grade B. The average daily cost of this drug was 8.082 yuan, and the price was low. The treatment cost accounted for a small proportion of the annual disposable income of urban and rural residents, indicating that it was affordable. Reyanning Mixture was available in 31 provinces, cities and autonomous regions, covering 6 910 hospitals. The allocation of hospitals at all levels was more than 50%. There was no shortage or supply restriction of medicinal material resources. The annual production capacity was sufficient to meet the supply demand, so its accessibility was grade A. Reyanning Mixture, sourced from "pneumonia Ⅲ", has been subjected to a real-world study of its clinical application, with 4 367 cases involved, and the characteristic of TCM was grade B. The comprehensive evaluation results demonstrated that the clinical value score of Reyanning Mixture in the treatment of acute upper respiratory tract infection(heat-toxin attacking lung syndrome) was 0.80, making it rated class A. According to the Guidelines for Management of Comprehensive Clinical Evaluation of Drugs(trial version 2021), it is recommended to convert it into the relevant policy results of basic clinical medication management according to the procedures.

Risk factors for hypocalcemia after parathyroidectomy in maintenance hemodialysis patients with secondary hyperparathyroidism / 中华肾脏病杂志

Objective:To explore the risk factors of hypocalcemia and the correlation between calcium supplementation and clinical parameters after parathyroidectomy (PTX) in maintenance hemodialysis patients with secondary hyperparathyroidism (SHPT), and to analyze the effect of calcium supplementation after PTX on the long-term prognosis of patients.Methods:This study was a single-center retrospective study. The patients who underwent PTX in maintenance hemodialysis patients with SHPT in the Huashan Hospital affiliated to Fudan University from October 2014 to March 2021 were retrospectively enrolled. Total PTX with auto transplantation or total PTX alone were the surgical procedures. According to the postoperative requirement of calcium in the first week, the patients were divided into two groups: high calcium supplement (>16.05 g/week) group and low calcium supplement group (≤16.05 g/week). According to the average serum calcium level in the first week after operation, the patients were divided into hypocalcemia group (≤2.1 mmol/L) and non-hypocalcemia group (>2.1 mmol/L) and the differences of clinical parameters between the two groups were compared. The correlation between clinical parameters and the postoperative calcium requirement was examined through Pearson or Spearman correlation analysis. The influencing factors for hypocalcemia after PTX were examined through logistic regression analysis. The survival curve was made by Kaplan-Meier method, and the difference of cumulative survival rate between the two groups was compared by log-rank test.Results:A total of 98 maintenance hemodialysis patients with SHPT were enrolled. The levels of serum calcium, phosphorus, and intact parathyroid hormone (iPTH) after the operation decreased significantly than those of preoperation (all P<0.05). Multiple linear regression analysis showed age ( β=-0.160, P=0.030), iPTH ( β=0.004, P=0.025) and C-reactive protein ( β=0.186, P=0.011) were correlated with postoperative calcium requirement. Preoperative alkaline phosphatase ( OR=1.002, 95% CI 1.000-1.004, P=0.018) and hemoglobin ( OR=0.977, 95% CI 0.954-1.000, P=0.048) independently predicted the occurrence risk of postoperative hypocalcemia through multivariate logistic regression analysis. The recurrence rate of high calcium supplement group was higher than that of low calcium supplement group (10.26% vs 0, P=0.023) and there was no significant difference in all-cause mortality between the two groups (17.95% vs 5.08%, P=0.086). The recurrence rate between the hypocalcemia group and non-hypocalcemia group was no significantly different (8.3% vs 1.8%, P=0.451) and there was no significant difference in all cause mortality between the two groups (12.5% vs 12.7%, P=1.000). Kaplan-Meier survival curve showed that the cumulative survival rate between the two groups was no significantly different (log-rank test χ2=0.147, P=0.702). Conclusions:PTX is a safe and effective therapeutic method to reduce the level of iPTH and improve the metabolism of calcium and phosphorus in SHPT patients. Age, iPTH and C-reactive protein are correlated with the postoperative requirement of calcium in the first week. Preoperative alkaline phosphatase and hemoglobin are independent risk factors for postoperative hypocalcemia. Correcting preoperative electrolyte disorder, improving infection and anemia can reduce the incidence of hypocalcemia after PTX.

Visualization of research on Chinese medicine-induced kidney injury by CiteSpace / 中国中药杂志

This study aimed to provide researchers with a better understanding of the research status, progress and problems of Chinese medicine-induced kidney injury. The mapping knowledge domain(MKD) was chosen to visualize the research process, hotspots,and frontiers, thus providing a reference for follow-up research. The relevant articles were retrieved from China National Knowledge Infrastructure(CNKI) from its inception to November 20, 2020, and 683 were finally included for visualization, with a knowledge map covering the keywords, research institutions and authors plotted by Cite Space. Since 2006, the annual number of published articles regarding Chinese medicine-induced kidney injury has steadily declined. The top five keywords sorted by frequency of co-occurrence were tubulointerstitial nephritis(TIN), aristolochic acid(AA), Akebiae Caulis, experimental research, and descriptive research. Akebiae Caulis appeared at the highest frequency of co-occurrence among Chinese medicines and exhibited the highest burst intensity. The burst ended in 2020, when the Chinese medicine with the highest burst intensity changed to Tripterygii wilfordii and its preparations. It could be seen that Akebiae Caulis was the hotspot in the research of Chinese medicine-induced kidney injury, and T. wilfordii became the research frontier. The current research has mainly focused on " organic anion transporters" and " metabolomics". The decline in articles about Chinese medicine-induced kidney injury was attributed to the reduced clinical case reports after the in-depth study of Chinese medicine-induced kidney injury. However, more clinical studies need to be conducted based on the concept and method of pharmacovigilance to construct a pharmacovigilance system of Chinese medicine for actively and passively monitoring and collecting the clinical cases with Chinese medicine-induced kidney injury, figuring out the incidence and characteristics of adverse reactions caused by Chinese medicine, and carrying out comprehensive and multi-dimensional safety research.

Analysis of Banxia Houpo Tang Based on Ancient Literatures / 中国实验方剂学杂志

Banxia Houpo Tang is widely used in modern clinics with definite curative effect. It is one of the classic famous prescriptions in the Catalogue of Ancient Classic Famous Recipes（First Batch） published by the State Administration of Traditional Chinese Medicine（TCM） in 2018. Using bibliometrics methods，collect relevant literatures of Banxia Houpo Tang in ancient medical books，analyze and verify the origin，historical evolution，composition，prescription，function，dosage，artillery，preparation method and decoction method of prescription. A total of 259 related ancient literature data were obtained，involving 107 TCM books. The inductive analysis found that Banxia Houpo Tang originated from ZHANG Zhong-jing's Synopsis of the Golden Chamberin the Han dynasty and consisted of the five flavors of Pinelliae Rhizoma，Magnoliae Officinalis Cortex，Poria，Perillae Folium and Zingiberis Rhizoma Recens. Houpo Tang，Qiqi Tang，Siqi Tang，Daqiqi Tang and other synonyms have appeared in the records of medical records of all dynasties. The prescription composition，preparation method and decoction method are used by later generations of medical practitioners. The analysis of related prescriptions is also rarely disputed. The dosage of drugs used in Banxia Houpo Tang can be calculated as 1g or 3 g. The drug processing method is different from the original one. Pinelliae Rhizoma should choose Pinelliae Rhizoma Praeparatum Cum Zingibere et Alumine and Magnoliae Officinalis Cortex as "Jianghoupu". The rest of the drug processing methods respect the 2015 edition of Chinese Pharmacopoeia. The cardiology of its treatment has also been extended and expanded. In addition to the symptoms of "burning in the pharynx" recorded by the original party，this side can also be used for heart diseases such as heartache，chest tightness，sorrow，vomiting，choking noisy and other spleen and stomach disease syndrome and spermatorrhea，turbidity，scorching and other lower coke disease syndrome.

Proteomics and peptidomics analysis of Sepiae Endoconcha / 中国中药杂志

Shotgun based proteomics and peptidomics analysis were used to investigate the proteins and peptides in marine traditional Chinese medicine(TCM) Sepiae Endoconcha(cuttlebone). Peptides were extracted from cuttlebone by acidified methanol, and then strong cation exchange(SCX) resin was used to enrich those peptides. Also, proteins from cuttlebone were extracted and digested by trypsin. nano-LC Q Exactive Orbitrap mass spectrometry was used to analyze proteins and peptides from cuttlebone. As a result, a total of 16 proteins and 168 peptides were identified by protein database search, and 328 peptides were identified by De novo sequencing. The identified proteins were hemocyanin, enolase, myosin, actin, calmodulin, etc., and the identified peptides were derived from actin, histone, and tubulin. All these proteins and peptides were important components in cuttlebone, which would provide important theoretical and research basis for marine TCM cuttlebone investigations.

Antioxidant status following postprandial challenge of two different doses of tocopherols and tocotrienols / 中西医结合学报

OBJECTIVE@#Tocotrienols (T3s) have been hypothesized to have greater antioxidant capacity than tocopherols (Ts) due to differences in biokinetics that affect their absorption and function. The present trial compares the antioxidant effectiveness following postprandial challenge of two different doses of α-T or palm T3-rich fraction (TRF) treatments and evaluates their dose-response effects on antioxidant status.@*METHODS@#Ten healthy volunteers were given four different doses of vitamin E formulations (268 mg α-T, 537 mg α-T, 263 mg TRF or 526 mg TRF) in a cross-over postprandial trial. Blood was sampled at 0, 2, 4, 5, 6 and 8 hours after meal consumption and plasma antioxidant status including total glutathione, superoxide dismutase, malondialdehyde (MDA), ferric reducing antioxidant potential and trolox-equivalent antioxidant capacity, was analyzed.@*RESULTS@#Supplementation with the different doses of either α-T or TRF did not significantly improve overall antioxidant status. There was no significant difference in overall antioxidant status among treatments at the different doses compared. However, a significant dose-response effect was observed for plasma MDA throughout the 8-hour postprandial period. MDA was significantly lower after the 537 mg α-T treatment, compared to the 268 mg α-T treatment; it was also lower after the 526 mg TRF treatment compared to the 263 mg TRF treatment (P < 0.05).@*CONCLUSION@#T3 and α-T demonstrated similar antioxidant capacity, despite markedly lower levels of T3 in blood and lipoproteins, compared to α-T.

Discussion on Use of Pinelliae Rhizoma Processed Products in Famous Classical Formulas / 中国实验方剂学杂志

There are 17 formulas containing Pinelliae Rhizoma in the Catalogue of Ancient Famous Classical Formulas (the First Batch), most of which are only labeled with " washing with decoction" or without any processing method, which is inconsistent with the current use requirements and brings confusion to research and development of related famous classical formulas. Through combing the records of famous classical formulas in the original book, contemporary works and later works, the usage of processed products of Pinelliae Rhizoma in the evolution of past dynasties was contrasted, and the efficacy, indications and compatibility significance of different formulas were analyzed, according to the principle of " respecting the ancient but not confining the ancient" , the authors suggested that the 17 famous classical formulas should use the processed products of Pinelliae Rhizoma in the 2015 edition of Chinese Pharmacopoeia, including Pinelliae Rhizoma Praeparatum, Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Pinelliae Rhizoma Praeparatum cum Alumine. Among them, Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine should be used in Banxia Xiexintang, Gancao Xiexintang, Huangliantang, Xuanfu Daizhe Tang, Zhuye Shigaotang, Banxia Houpotang, Maimendong Tang, Gualou Xiebai Banxiatang, Wendantang, Zhurutang, Jinshui Liujun Jian and Yangweitang, Pinelliae Rhizoma Praeparatum should be used in Shengyang Yiweitang, Houpo Mahuangtang, Banxia Baizhu Tianma Tang and Huopo Xialing Tang, and Pinelliae Rhizoma Praeparatum cum Alumine should be used in Sangbaipi Tang.