Radiomics model based on CT images for distinguishing invasive lung adenocarcinoma with micropapillary or solid structure / 中国胸心血管外科临床杂志

@#Objective    To investigate the radiomics features to distinguish invasive lung adenocarcinoma with micropapillary or solid structure. Methods    A retrospective analysis was conducted on patients who received surgeries and pathologically confirmed invasive lung adenocarcinoma in our hospital from April 2016 to August 2019. The dataset was randomly divided into a training set [including a micropapillary/solid structure positive group (positive group) and a micropapillary/solid structure negative group (negative group)] and a testing set (including a positive group and a negative group) with a ratio of 7∶3. Two radiologists drew regions of interest on preoperative high-resolution CT images to extract radiomics features. Before analysis, the intraclass correlation coefficient was used to determine the stable features, and the training set data were balanced using synthetic minority oversampling technique. After mean normalization processing, further radiomics features selection was conducted using the least absolute shrinkage and selection operator algorithm, and a 5-fold cross validation was performed. Receiver operating characteristic (ROC) curves were depicted on the training and testing sets to evaluate the diagnostic performance of the radiomics model. Results    A total of 340 patients were enrolled, including 178 males and 162 females with an average age of 60.31±6.69 years. There were 238 patients in the training set, including 120 patients in the positive group and 118 patients in the negative group. There were 102 patients in the testing set, including 52 patients in the positive group and 50 patients in the negative group. The radiomics model contained 107 features, with the final 2 features selected for the radiomics model, that is, Original_ glszm_ SizeZoneNonUniformityNormalized and Original_ shape_ SurfaceVolumeRatio. The areas under the ROC curve of the training and the testing sets of the radiomics model were 0.863 (95%CI 0.815-0.912) and 0.857 (95%CI 0.783-0.932), respectively. The sensitivity was 91.7% and 73.7%, the specificity was 78.8% and 84.0%, and the accuracy was 85.3% and 78.4%, respectively. Conclusion    There are differences in radiomics features between invasive pulmonary adenocarcinoma with or without micropapillary and solid structures, and the radiomics model is demonstrated to be with good diagnostic value.

Study on the application of model transfer technology in the extraction process of Xiao'er Xiaoji Zhike oral liquid / 药学学报

The modernization and development of traditional Chinese medicine has led to higher standards for the quality of traditional Chinese medicine products. The extraction process is a crucial component of traditional Chinese medicine production, and it directly impacts the final quality of the product. However, the currently relied upon methods for quality assurance of the extraction process, such as simple wet chemical analysis, have several limitations, including time consumption and labor intensity, and do not offer precise control of the extraction process. As a result, there is significant value in incorporating near-infrared spectroscopy (NIRS) in the production process of traditional Chinese medicine to improve the quality control of the final products. In this study, we focused on the extraction process of Xiao'er Xiaoji Zhike oral liquid (XXZOL), using near-infrared spectra collected by both a Fourier transform near-infrared spectrometer and a portable near-infrared spectrometer. We used the concentration of synephrine, a quality control index component specified by the pharmacopoeia, to achieve rapid and accurate detection in the extraction process. Moreover, we developed a model transfer method to facilitate the transfer of models between the two types of near-infrared spectrometers (analytical grade and portable), thus resolving the low resolution, poor performance, and insufficient prediction accuracy issues of portable instruments. Our findings enable the rapid screening and quality analysis of XXZOL onsite, which is significant for quality monitoring during the traditional Chinese medicine production process.

Protective effects of three kinds of borneol on different brain regions in acute cerebral ischemia/reperfusion model rats / 中国中药杂志

This study compared the ameliorating effects of L-borneol, natural borneol, and synthetic borneol on the injury of different brain regions in the rat model of acute phase of cerebral ischemia/reperfusion(I/R) for the first time, which provides a reference for guiding the rational application of borneol in the early treatment of ischemic stroke and has important academic and application values. Healthy specific pathogen-free(SPF)-grade SD male rats were randomly assigned into 13 groups: a sham-operation group, a model group, a Tween model group, a positive drug(nimodipine) group, and high-, medium-, and low-dose(0.2, 0.1, and 0.05 g·kg~(-1), respectively) groups of L-borneol, natural borneol, and synthetic borneol according to body weight. After 3 days of pre-administration, the rat model of I/R was established by suture-occluded method and confirmed by laser speckle imaging. The corresponding agents in different groups were then administered for 1 day. The body temperature was monitored regularly before pre-administration, days 1, 2, and 3 of pre-administration, 2 h after model awakening, and 1 d after model establishment. Neurological function was evaluated based on Zea-Longa score and modified neurological severity score(mNSS) 2 h and next day after awakening. The rats were anesthetized 30 min after the last administration, and blood was collected from the abdominal aorta. Enzyme-linked immunoassay assay(ELISA) was employed to determine the serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-4, and transforming growth factor-beta1(TGF-β1). The brain tissues were stained with triphenyltetrazolium chloride(TTC) for the calculation of cerebral infarction rate, and hematoxylin-eosin(HE) staining was used for observing and semi-quantitatively evaluating the pathological damage in different brain regions. Immunohistochemistry was employed to detect the expression of ionized calcium binding adapter molecule 1(IBA1) in microglia. q-PCR was carried out to determine the mRNA levels of iNOS and arginase 1(Arg1), markers of polarization phenotype M1 and M2 in microglia. Compared with the sham-operation group, the model group and the Tween model group showed significantly elevated body temperature, Zea-Longa score, mNSS, and cerebral infarction rate, severely damaged cortex, hippocampus, and striatum, increased serum levels of IL-6 and TNF-α, and decreased serum levels of IL-4 and TGF-β1. The three borneol products had a tendency to reduce the body temperature of rats 1 day after modeling. Synthetic borneol at the doses of 0.2 and 0.05 g·kg~(-1), as well as L-borneol of 0.1 g·kg~(-1), significantly reduced Zea-Longa score and mNSS. The three borneol products at the dose of 0.2 g·kg~(-1) significantly reduced the cerebral infarction rate. L-borneol at the doses of 0.2 and 0.1 g·kg~(-1) and natural borneol at the dose of 0.1 g·kg~(-1) significantly reduced the pathological damage of the cortex. L-borneol and natural borneol at the dose of 0.1 g·kg~(-1) attenuated the pathological damage of hippocampus, and 0.2 g·kg~(-1) L-borneol attenuated the damage of striatum. The 0.2 g·kg~(-1) L-borneol and the three doses of natural borneol and synthetic borneol significantly reduced the serum level of TNF-α, and the 0.1 g·kg~(-1) synthetic borneol reduced the level of IL-6. L-borneol and synthetic borneol at the dose of 0.2 g·kg~(-1) significantly inhibited the activation of cortical microglia, and 0.2 g·kg~(-1) L-borneol up-regulated the expression of Arg1 and down-regulated the expression level of iNOS. In conclusion, the three borneol products may alleviate inflammation to ameliorate the pathological damage of brain regions of rats in the acute phase of I/R by inhibiting the activation of microglia and promoting the polarization of microglia from M1 type to M2 type. The protective effect on brain followed a trend of L-borneol > synthetic borneol > natural borneol. We suggest L-borneol the first choice for the treatment of I/R in the acute phase.

Research progress of Shegan Mahuang Decoction and predictive analysis on its Q-markers / 中国中药杂志

Shegan Mahuang Decoction has been used in clinical practice for thousands of years, and is a classical formula for treating asthma and other respiratory diseases, with the effects of ventilating lung, dispersing cold, and relieving cough and asthma. This paper summarized the history, clinical application and mechanism of Shegan Mahuang Decoction, and predicted its quality markers(Q-markers) based on the "five principles" of Q-markers. The results suggested that irisflorentin, tectoridin, tectorigenin, irigenin, ephedrine, pseudoephedrine, asarinin, methyleugenol, shionone, epifriedelanol, tussilagone, 6-gingerol, trigonelline, cavidine, schizandrin, and schizandrin B could be used as Q-markers of Shegan Mahuang Decoction, which provided a basis for the quality control and subsequent research and development of Shegan Mahuang Decoction.

Effect and mechanism of Bovis Calculus on ulcerative colitis by inhibiting IL-17/IL-17RA/Act1 signaling pathway / 中国中药杂志

This study aimed to elucidate the effect and underlying mechanism of Bovis Calculus in the treatment of ulcerative colitis(UC) through network pharmacological prediction and animal experimental verification. Databases such as BATMAN-TCM were used to mine the potential targets of Bovis Calculus against UC, and the pathway enrichment analysis was conducted. Seventy healthy C57BL/6J mice were randomly divided into a blank group, a model group, a solvent model(2% polysorbate 80) group, a salazosulfapyridine(SASP, 0.40 g·kg~(-1)) group, and high-, medium-, and low-dose Bovis Calculus Sativus(BCS, 0.20, 0.10, and 0.05 g·kg~(-1)) groups according to the body weight. The UC model was established in mice by drinking 3% dextran sulfate sodium(DSS) solution for 7 days. The mice in the groups with drug intervention received corresponding drugs for 3 days before modeling by gavage, and continued to take drugs for 7 days while modeling(continuous administration for 10 days). During the experiment, the body weight of mice was observed, and the disease activity index(DAI) score was recorded. After 7 days of modeling, the colon length was mea-sured, and the pathological changes in colon tissues were observed by hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), and interleukin-17(IL-17) in colon tissues of mice were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA expression of IL-17, IL-17RA, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, CXCL2, and CXCL10 was evaluated by real-time polymerase chain reaction(RT-PCR). The protein expression of IL-17, IL-17RA, Act1, p-p38 MAPK, and p-ERK1/2 was investigated by Western blot. The results of network pharmacological prediction showed that Bovis Calculus might play a therapeutic role through the IL-17 signaling pathway and the TNF signaling pathway. As revealed by the results of animal experiments, on the 10th day of drug administration, compared with the solvent model group, all the BCS groups showed significantly increased body weight, decreased DAI score, increased colon length, improved pathological damage of colon mucosa, and significantly inhibited expression of TNF-α,IL-6,IL-1β, and IL-17 in colon tissues. The high-dose BCS(0.20 g·kg~(-1)) could significantly reduce the mRNA expression levels of IL-17, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, and CXCL2 in colon tissues of UC model mice, tend to down-regulate mRNA expression levels of IL-17RA and CXCL10, significantly inhibit the protein expression of IL-17RA,Act1,and p-ERK1/2, and tend to decrease the protein expression of IL-17 and p-p38 MAPK. This study, for the first time from the whole-organ-tissue-molecular level, reveals that BCS may reduce the expression of pro-inflammatory cytokines and chemokines by inhibiting the IL-17/IL-17RA/Act1 signaling pathway, thereby improving the inflammatory injury of colon tissues in DSS-induced UC mice and exerting the effect of clearing heat and removing toxins.

Dorsal plate assisted fixation of dorsal lunate fossa fracture of distal radius / 中国骨伤

OBJECTIVE@#To explore clinical efficacy of dorsal plate assisted fixation of dorsal lunate fossa fracture block of distal radius.@*METHODS@#From January 2019 to January 2022, 30 patients were treated with dorsal plate assisted fixation of dorsal lunate fossa fracture of distal radius, including 13 males and 17 females, aged from 42 to 68 years old with an average of (48.7±5.6) years old;According to Doi fracture classification, 24 patients were type 3 blocks and 6 patients were type 4 blocks. The degree of palmar angle of anterior and posterior distal radius was fixed by dorsal steel plate during operation. Fracture healing and functional recovery of wrist were observed after operation. Functional evaluation was performed by Gartland and Werley scoring system at 12 months after operation.@*RESULTS@#All patients were followed up from 12 to 13 months with an average of (11.3±0.9) months. All fractures healed for 4 to 5 months with an average of(4.7±0.8) months. Median palpal inclination of anterior and posterior distal radius fixed by dorsal plate was 5.30°(4.85°, 6.03°), 12.45°(11.98°, 13.43°) respectively, and had statistical difference( P<0.01). Gartland and Werley scores was (1.1±0.4) at 12 months afteropertaion, and 27 patients got excellent result and 3 good.@*CONCLUSION@#Dorsal plate assisted fixation of dorsal lunate fossa fractures is beneficial to reduction and stabilization of displaced dorsal fractures and restoration of palmar inclination.

Advancements in virtual screening techniques for study of enzyme inhibitor compounds / 中国中药杂志

Enzymes are closely associated with the onset and progression of numerous diseases, making enzymes a primary target in innovative drug development. However, the challenge remains in identifying compounds that exhibit potent inhibitory effects on the target enzymes. With the continuous expansion of the total number of natural products and increasing difficulty in isolating and enriching new compounds, traditional high-throughput screening methods are finding it increasingly challenging to meet the demands of new drug development. Virtual screening, characterized by its high efficiency and low cost, has gradually become an indispensable technology in drug development. It represents a prominent example of the integration of artificial intelligence with biopharmaceuticals and is an inevitable trend in the rapid development of innovative drug screening in the future. Therefore, this article primarily focused on systematically reviewing the recent applications of virtual screening technology in the development of enzyme inhibitors and explored the prospects and advantages of using this technology in developing new drugs, aiming to provide essential theoretical insights and references for the application of related technologies in the field of new drug development.

Improvement effect of Shegan Mahuang Decoction on rats with cold-induced asthma based on TRPV1/NRF-1/mtTFA pathway / 中国中药杂志

This study investigated the therapeutic effect of Shegan Mahuang Decoction(SGMHD) on cold-induced asthma in rats and explored its underlying mechanism. Seventy-two healthy male SD rats of specific pathogen free(SPF) grade were randomly divided into a blank group, a model group, a positive control group(dexamethasone, 0.4 mg·kg~(-1)), and low-, medium-, and high-dose SGMHD groups(3.2, 6.4, and 12.8 g·kg~(-1)). The blank group received saline, while the other groups were sensitized by intraperitoneal injection of ovalbumin(OVA) solution. Subsequently, the rats were placed in a cold chamber adjustable to 0-2 ℃, and OVA solution was ultrasonically nebulized to induce cold-induced asthma in rats. After three weeks of treatment, the general behaviors of rats were observed. Hematoxylin-eosin(HE) staining was used to evaluate pathological changes in lung tissues, periodic acid-Schiff(PAS) staining assessed mucin changes, and Masson staining was performed to examine collagen deposition. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of the inflammatory factors interleukin-4(IL-4) and vascular endothelial growth factor(VEGF) in serum and bronchoalveolar lavage fluid(BALF). Real-time quantitative polymerase chain reaction(RT-PCR) was employed to assess the mRNA expression levels of transient receptor potential vanilloid subfamily member 1(TRPV1), nuclear respiratory factor 1(NRF-1), and mitochondrial transcription factor A(mtTFA) in lung tissues. Western blot was used to measure the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues. Compared with the blank group, the model group exhibited signs of rapid respiration, increased frequency of defecation with looser stools, and disheveled and dull fur. Pathological results showed significant infiltration of inflammatory cells in lung tissues, narrowing of bronchial lumens, increased mucin secretion, and enhanced collagen deposition in the model group. Additionally, the levels of IL-4 and VEGF in serum and BALF were significantly elevated, and the mRNA and protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were significantly increased. Compared with the model group, SGMHD improved the behaviors of rats, alleviated pathological changes in lung tissues, mucin production, and collagen deposition, significantly decreased the levels of IL-4 and VEGF in serum and BALF, and reduced the mRNA expression levels of TRPV1, NRF-1, and mtTFA in lung tissues, with the medium-dose SGMHD group showing the most significant effect. Moreover, the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were also reduced, with the medium-dose SGMHD group exhibiting the most significant effect. In conclusion, this study demonstrates that SGMHD can alleviate airway inflammation and inhibit airway remodeling in cold-induced asthma rats. These effects may be associated with the modulation of the TRPV1/NRF-1/mtTFA signaling pathway.

Chemical constituents and mechanism of Chuanzhi Tongluo Capsules based on UPLC-Q-Exactive Orbitrap-MS and network pharmacology / 中国中药杂志

The chemical constituents of Chuanzhi Tongluo Capsules were analyzed and identified using ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) to clarify the pharmacological substance basis. In addition, network pharmacology was employed to explore the mechanism of Chuanzhi Tongluo Capsules in the treatment of cerebral infarction. Gradient elution was performed using acetonitrile and 1% acetic acid in water as the mobile phase. Mass spectrometry was performed in positive and negative ion modes. Xcalibur 4.2 software was used for compound analysis, including accurate mass-to-charge ratio and MS/MS fragment information, combined with the comparison of reference standards and literature data. A total of 152 compounds were identified, including 32 organic acids, 35 flavonoids and their glycosides, 33 diterpenes, 13 phthalides, 12 triterpenes and triterpene saponins, 23 nitrogen-containing compounds, and 4 other compounds, and their fragmentation patterns were analyzed. SwissTargetPrediction, GeneCards, DAVID, and other databases were used to predict and analyze the core targets and mechanism of Chuanzhi Tongluo Capsules. Protein-protein interaction(PPI) network topology analysis identified 10 core targets, including TNF, VEGFA, EGFR, IL1B, and CTNNB1. KEGG enrichment analysis showed that Chuanzhi Tongluo Capsules mainly exerted their effects through the regulation of lipid and atherosclerosis, glycoproteins in cancer, MicroRNAs in cancer, fluid shear stress, and atherosclerosis-related pathways. Molecular docking was performed between the key constituents and core targets, and the results demonstrated a strong binding affinity between the key constituents of Chuanzhi Tongluo Capsules and the core targets. This study comprehensively elucidated the chemical constituents of Chuanzhi Tongluo Capsules and explored the core targets and mechanism in the treatment of cerebral infarction based on network pharmacology, providing a scientific reference for the study of the pharmacological substance basis and formulation quality standards of Chuanzhi Tongluo Capsules.

A single-center retrospective analysis of surgical strategy and clinical outcome of pulmonary nodules using pulmonary subsegments as anatomical unit / 中国胸心血管外科临床杂志

@#Objective    To analyze the results and rationality of the lesion-focused strategy with subsegment as the pulmonary anatomical unit for pulmonary nodules with a diameter of ≤2 cm which require surgery. Methods    Clinical data of 246 patients with pulmonary nodules who underwent surgery in the Department of Thoracic Surgery of The First Affiliated Hospital of Nanjing Medical University from January 2017 to October 2018 were retrospectively analyzed, including 76 males and 170 females, with an average age of 53.30±11.82 years. The patients were divided into four groups, a single segmentectomy group, a segmentectomy combined with adjacent subsegmentectomy group, a single subsegmentectomy group and a combined subsegmentectomy group, according to the different surgical approaches, to compare preoperative, intraoperative, and postoperative related data. Results    There was no perioperative death. Among the four groups, there was no statistical difference in gender (P=0.163), age (P=0.691), diameter of the nodule (P=0.743), longitudinal position of the nodule (depth ratio, P=0.831), postoperative pulmonary leakage (P=0.752), intraoperative blood loss (P=0.135), pathological type (P=0.951) or TNM stage (P=0.995); there were statistical differences in transverse position of the nodule (P<0.001) and number of subsegments involved (P<0.001). The results of multivariate logistic regression analysis showed that compared with combined subsegmentectomy, the odds ratio (OR) of the lung nodule in segmentectomy combined with adjacent subsegmentectomy as intersegment nodules was 5.759 (95%CI 1.162 to 28.539, P=0.032). Conclusion     The surgical strategy of lesion  focused and subsegment as anatomical unit is safe and feasible for surgical treatment of pulmonary nodules with diameter ≤2 cm. The transverse position of the nodules is an important factor affecting the choice of surgical method for the middle and lateral nodules with a diameter of ≤2 cm, and the longitudinal location of the nodule is not an influencing factor. For nodules in inner zone, the diameter also is one of the factors influencing the choice of surgical method.

Study on the apoptosis of human retinal pigment epithelium cells induced by EGCG / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the effect of epigallocatechin gallate(EGCG)on the apoptosis of human retinal pigment epithelium(ARPE-19)cells and its mechanism. METHODS:The ARPE-19 cells were cultured in vitro and treated with 0,40,80 and 160 μg/mL EGCG, respectively. At the proposed time of treatment the morphological changes were detected by hoechst 33258 staining. The apoptosis rate was detected by flow cytometry. The expression of apoptosis-related factors B lymphocytoma-2 gene(bcl-2), BCL2-Associated X protein(Bax),caspase-3 and p53 were detected by quantitative RT-PCR and Western blotting.RESULTS: Hoechst 33258 staining showed that the ARPE-19 cells with the increase of EGCG drug concentration, the number of apoptotic cells gradually increased and the apoptotic bodies were observed. Flow cytometry showed that the apoptosis rate increased gradually with the increase of EGCG drug concentration. The apoptosis rates at 40, 80 and 160 μg/mL were 4.95%±0.071%, 11.75%±0.075% and 21.25%±0.919% respectively, which was significantly different compared with the control group(2.8%±1.556%)(P<0.01), presented with a drug concentration-dependent. The results of quantitative PCR and Western blotting showed that EGCG could significantly up-regulate the expression of apoptosis-promoting factors Bax, caspase-3 and the mRNA and protein expression of p53, and down-regulate the apoptosis-inhibiting factor bcl-2, all of these showed concentration-dependent effects.CONCLUSION:EGCG can obviously induce the apoptosis of ARPE-19 cells. The mechanism is related with the inhibition of bcl-2 and increase the expression of Bax, caspase-3 and p53.

Clinical Characteristics and Risk Factors Analysis for Visceral Pleural Invasion in Mixed Ground-glass Nodular Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#Lung cancer is still the malignant tumor with the highest morbidity and mortality in China. Lung adenocarcinoma is the most common subtype, and the number of lung cancer presenting as mixed ground glass nodule (mGGN) in imaging is gradually increasing. Visceral pleural invasion (VPI) is an important factor affecting the prognosis of mGGN type lung adenocarcinoma. The aim of the study is to explore and analyze the risk factors for VPI in mGGN type lung adenocarcinoma.@*METHODS@#From November 2016 to November 2019, 128 patients with mGGN lung adenocarcinoma underwent radical surgical resection in the First Affiliated Hospital of Nanjing Medical University. Their clinical data, including imaging, pathological and biological features, were collected and analyzed retrospectively. There were 40 males and 88 females, aged 60.3±9.3 years ranging from 30 to 81 years. Single factor Chi-square test and multivariate Logistic regression were used to analyze the risk factors of VPI in mGGN type lung adenocarcinoma.@*RESULTS@#Among 128 mGGN patients who met the inclusion criteria, 57 cases were pathologically confirmed with pleural invasion. Between the VPI (+) and VPI (-) group (P<0.05), there were significant differences in gender, maximum diameter of solid component, consolidation tumor ratio (CTR), spicule sign, history of lung disease, family history of hypertension, relation of lesion to pleura (RLP), coursing relationship between bronchi and nodules. In multivariate Logistic regression analysis, RLP (OR=3.529, 95%CI: 1.430-8.713, P=0.006) and coursing relationship between bronchi and nodules (OR=3.993, 95%CI: 1.517-10.51, P=0.005) were found to be independent risk factors for VPI (P<0.05).@*CONCLUSIONS@#The possibility of VPI in m GGN lung adenocarcinoma should be evaluated by combining these parameters in clinical diagnosis and treatment. As independent risk factors, RLP and coursing relationship between bronchi and nodules are instructive to identify VPI in mGGN type lung adenocarcinoma.

Phenylpropanoids from Zanthoxylum species and their pharmacological activities: a review / 中国中药杂志

Phenylpropanoids are one of the major chemical constituents in Zanthoxylum species. They include simple phenylpropanoids, coumarins, and lignans and possess anti-tumor, anti-inflammatory, anti-platelet aggregation, anti-bacterial, anti-viral, insecticidal, and antifeedant activities. This review summarizes the chemical constituents and pharmacological activities from the Zanthoxylum plants in hopes of providing reference for the research and application of phenylpropanoids from this genus.

Effect of Echinococcus multilocularis infections on mitochondrial functions of macrophages / 中国血吸虫病防治杂志

Objective To investigate the changes of mitochondrial metabolic functions of macrophages following Echinococcus multilocularis infections, so as to provide insights into the pathogenesis of alveolar echinococcosis. Methods Two groups were assigned according to different treatment methods. In the culture group, mouse leukemic monocyte macrophage RAW264.7 cells were cultured with 2 000 E. multilocularis at a ratio of 500∶1, while RAW264.7 cells in the control group were given no treatment. Then, both the culture and control groups were further divided into the 24 h and 72 h subgroups. Mitochondria were stained with MitoTracker® Deep Red FM and the mean fluorescence intensity of macrophage mitochondria was measured with the Cytation 5 Cell Imaging Multi-Mode Reader. The mitochondrial DNA copy number was quantified using the quantitative real-time PCR (qPCR) assay, and the mitochondrial energy metabolism was monitored using the Seahorse XF assay. In addition, the mitochondrial reactive oxygen species and mitochondrial membrane potential were detected using flow cytometry. Results The mean fluorescence intensities of macrophage mitochondria were significantly lower in the 24 h (15 341 ± 2 532 vs. 17 823 ± 3 429; t = 6.379, P < 0.01) and 72 h (18 102 ± 3 505 vs. 21 511 ± 5 144; t = 17.680, P < 0.01) culture subgroups than in the corresponding control subgroups, and lower mitochondrial DNA copy numbers were measured in the 72 h culture subgroup than in the 72 h control group [(3.23 × 109 ± 1.78 × 107) vs. (4.39 × 109 ± 3.70 × 107); t = 8.85, P < 0.001]. The oxygen consumption rates were significantly greater in the 24 h [(241.70 ± 73.13) pmol/min vs. (69.05 ± 52.30) pmol/min; t = 7.89, P < 0.01] and 48 h culture groups [(249.50 ± 42.06) pmol/min vs. (60.28 ± 40.66) pmol/min; t = 8.64, P < 0.01] than in the corresponding control groups, and a higher extracellular acidification rate was seen in the 48 h culture group than in the 48 h control group ([ 111.6 ± 17.49) mpH/min vs. (35.05 ± 7.57) mpH/min; t = 16.90, P < 0.01]. In addition, flow cytometry detected higher mean fluorescence intensity of mitochondrial reactive oxygen species (58 264 ± 10 087 vs. 4 307 ± 97; t = 12.930, P < 0.01) and lower mitochondrial membrane potential (9.833% ± 2.285% vs. 2.667% ± 0.208%; t = 6.645, P < 0.01) in the 72 h culture group than in the control group. Conclusions E. multilocularis infection may impair mitochondrial functions and inhibit oxidative phosphorylation of macrophages, resulting in increased macrophage glycolysis. It is speculated that the alteration of macrophage metabolic states may contribute to the mechanisms underlying the development and progression of alveolar echinococcosis.

Identification of pulmonary nodule location in three dimensional images and its clinical significance / 中国胸心血管外科临床杂志

@#Objective    To analyze the difference of location identification of pulmonary nodules in two dimensional (2D) and three dimensional (3D) images, and to discuss the identification methods and clinical significance of pulmonary nodules location in 3D space. Methods    The clinical data of 105 patients undergoing sublobectomy in the Department of Thoracic Surgery, the First Affiliated Hospital with Nanjing Medical University from December 2018 to December 2019 were analyzed retrospectively. There were 28 males and 77 females, with an average age of 57.21±13.19 years. The nodule location was determined by traditional 2D method and 3D depth ratio method respectively, and the differences were compared. Results    A total of 30 nodules had different position identification between the two methods, among which 25 nodules in the inner or middle zone of 2D image were located in the peripheral region of 3D image. The overall differences between the two methods were statistically significant (P<0.05). The diagnostic consistency rates of two methods were 66.67% in the right upper lung, 83.33% in the right middle lung, 73.68% in the right lower lung, 75.76% in the left upper lung, and 64.71% in the left lower lung. In each lung lobe, the difference between the two methods in the right upper lung (P=0.014) and the left upper lung (P=0.019) was statistically significant, while in the right middle lung (P=1.000), right lower lung (P=0.460) and left lower lung (P=0.162) were not statistically significant. Conclusion    The 3D position definition of lung nodules based on depth ratio is more accurate than the traditional 2D definition, which is helpful for preoperative planning of sublobectomy.

Development and validation of antibody sandwich enzyme-linked immunosorbent assay method for quantitation of GeXIVA1,2 in plasma of rats and Beagle dogs / 药学学报

GeXIVA[1,2] is a new type of conotoxin recently discovered in the transcriptome of Conus generalis and it is expected to be used clinically as a new type of analgesic. This study established and verified a sandwich enzyme-linked immunosorbent assay method for the marine drug GeXIVA[1,2] in the plasma of rats and Beagle dogs. The mouse monoclonal antibody 4B2 and biotin-labeled rabbit polyclonal antibody 2# were developed. The checkerboard method was used to optimize the antibody pairing concentration, minimum dilution ratio, incubation temperature, and incubation time to establish an antibody sandwich ELISA detection method. Verify the established testing methods. The established ELISA method has a quantitative range of 1.25-80 ng·mL-1 in rat and Beagle plasma. The precision, accuracy, selectivity, specificity, stability, dilution linearity, and hook effect all meet the requirements for biological sample analysis. All the procedures for the animal experiments were approved by the Animal Ethics Committee of the Institute (Permit Number: IACUC-DWZX-2020-698). This method can support the preclinical pharmacokinetic study of the marine drug GeXIVA.

Characterization of Echinostoma miyagawai in domestic ducks in Wuhu City / 中国血吸虫病防治杂志

Objective To investigate the morphological characteristics of Echinostoma miyagawai in domestic ducks in Wuhu area, and to explore the feasibility of the cytochrome oxidase subunit-1 (Cox1) gene as a molecular marker for the identification of E. miyagawai. Methods E. miyagawai was isolated from free-ranged domestic ducks in Wuhu area, and the parasites were stained and identified. In addition, the mitochondrial Cox1 gene of E. miyagawai was amplified using a PCR assay, and the amplification product was sequenced and aligned with the GenBank database to yield the homology for the identification of parasite species in combination with morphological findings. Intra-species comparison was done based on the Cox1 gene sequence. Results The prevalence of E. miyagawai infection was 16.67% in domestic ducks in Wuhu area, and the adult E. miyagawai was 6.6 to 13.2 mm in length. The size of the E. miyagawai Cox1 gene was approximately 660 bp, which had a 99.68% homology to the E. miyagawai accessed in GenBank. The morphological findings were in agreement with molecular identification. Conclusion E. miyagawai infection is common in domestic ducks in Wuhu area, and the mitochondrial Cox1 gene is a feasible marker of intra- and inter-species molecular identification of Echinostoma.

Clinical Observation of Addition and Subtraction Therapy of Taohong Siwutang Combined with Chaihu Shugansan to Unstable Angina Pectoris with Type A Behavior Pattern / 中国实验方剂学杂志

Objective: To observe the clinical efficacy of addition and subtraction therapy of Taohong Siwutang combined with Chaihu Shugansan to unstable angina pectoris with type A behavior pattern (Qi stagnation and blood stasis syndrome), and investigate its effects on proinflammatory factors and serotonin (5-HT). Method: One hundred twenty-four patients were randomly divided into control group (60 cases) and observation group(64 cases) by random number table. Patients in control group got Aspirin enteric-coated tablets, 100 mg/time, 1 time/day. Tigrillo tablets, 90 mg/time, 2 times/days. Metoprolol tartrate tablets, 50 mg/time, 2 times/days. Simvastatin tablets, 10 mg/time, 1 time/day. Nitroglycerin tablets, 0.5 mg/time. Based on the treatment in control group, patients in observation group also received addition and subtraction therapy of Taohong Siwutang combined with Chaihu Shugansan, 1 dose/day. The treatment course was 8 weeks in both groups. Number of attacks, duration, degree of pain and usage of nitroglycerin were recorded for every week. Before and after treatment, electrocardiogram was also recorded. And levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), hypersensitive C-reactive protein and 5-HT were detected. In addition, scores of Seattle Angina Scale (SAQ) and Qi stagnation and blood stasis syndrome were graded. Result: In the rank sum test, the curative effect in electrocardiogram of observation group was better than that of control group (Z=1.965, PPPPα and 5-HT in observation group were lower than those in control group (PPConclusion: On the basis of conventional western medicine, addition and subtraction therapy of Taohong Siwutang combined with Chaihu Shugansan can further control angina attack, relieve clinical symptoms, improve quality of life, regulate lipid metabolism, and can inhibit expression of proinflammatory factors and 5-HT, so it can play a role in stabilizing the disease.

Anti-tumor experimental study of mouse multi-subtype heat shock protein/peptide vaccine combined with PD-L1 immunological checkpoint inhibitor / 中国肿瘤临床

Objective: To evaluate the anti-tumor activity of mouse multi-subtype heat shock protein/peptide (mHSP/P) vaccine in combination with a programmed death ligand 1 (PD-L1) inhibitor in mouse sarcoma. Methods: Immunohistochemical staining and en-zyme-linked immunosorbent assay (Elisa) was used to quantitatively identify the expression of heat shock proteins (HSP70, HSP90, Grp94) in the sarcoma cell line MCA207. From the protein suspension prepared, mHSP/P and Grp94/peptide (Grp94/P) sarcoma vac-cines were isolated using chromatography and were identified by Western blot (WB). Flow cytometry was used to determine their cy-totoxic effects. The levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) produced upon mHSP/P and Grp94/P stimulation were measured by Elisa. The effect of sarcoma vaccines on the growth and survival of sarcoma was evaluated in mice. The expression of PD-L1 on the surface of MCA207 sarcoma cells was evaluated by immunofluorescent staining. The effect of IFN-γ treatment on the expression of PD-L1 was determined by WB. Animal experiments explored the effects of PD-L1 inhibitor in combination with mHSP/P treatment on tumors. Results: Tumor tissue carries a variety of HSP subtypes (HSP70, HSP90, Grp94). We successfully isolated sarco-ma tissue-derived mHSP/P and Grp94/P tumor vaccines, which were identified by WB; flow cytometry analysis demonstrated their cy-totoxicity. The levels of IFN-γ and TNF-α cytokines upon mHSP/P stimulation were significantly higher than that observed upon Grp94/P stimulation (P<0.05). The expression of PD-L1 on the surface of sarcoma cells increased with IFN-γ treatment. Animal experiments demonstrated that PD-L1 inhibitor in combination with mHSP/P significantly increased the immune response against tumor (P<0.05). Conclusions: Tumor-derived mHSP/P and Grp94/P can be used as tumor vaccines in animal models. The mHSP/P can elicit a stronger anti-tumor immune response than Grp94/P. IFN-γ stimulates the expression of PD-L1 in sarcoma cells, which results in immune eva-sion. The PD-L1 inhibitor in combination with mHSP/P increased the anti-tumor effect in the tumor microenvironment.

Differential value of CT quantitative analysis for different subtypes of invasive lung adenocarcinoma presenting as subsolid nodule / 实用放射学杂志

Objective To explore the value of CT quantitative analysis in differentiating lepidicGpredominant adenocarcinoma (LPA)from invasive nonGlepidicGpredominant adenocarcinoma (INV)manifested as subsolid nodules (SSN).Methods A total of patients with lung adenocarcinoma manifested as SSNs on CT images were divided into LPA group and INV group according to their pathological results.Total volume,solid volume,solid volume percentage,total mass,solid mass,solid mass percentage and threeGdimensional mean CT value of the nodules were calculated after segmenting pulmonary nodules by a 3DGCT segmentation software,meanwhile the oneGdimensional mean CT value and maximal diameter were manually measured.SPSS 22.0 software was used for statistical analysis. Results Solid volume (0.1 6 ±0.3 6 cm3 vs 1.2 6 ±2.1 7 cm3 ,P＜0.00 1),solid volume percentage (4.7 9 ±5.40% vs 2 6.3 3 ± 1 5.6 3%, P＜0.001),total mass (1 180.64±1 751.46 mg vs 2 386.59±3 224.54 mg,P＝0.010),solid mass (151.64±337.53 mg vs 1 257.34± 2 220.9 2 mg,P＜0.00 1 ),solid mass percentage (7.9 8 ± 8.5 8% vs 3 7.2 3 ± 1 8.83%,P＜0.00 1 ),threeGdimensional mean CT value (－492.26±71.21 HU vs －350.73±94.52 HU,P＜0.001 )and oneGdimensional mean CT value (－472.29 ± 1 12.46 HU vs －282.02 ± 1 5 9.13 HU,P＜0.001)in LPA group were found significantly lower than those in INV group.There were no significant differences in the maximal diameter and total volume between LPA group and INV group.Solid volume percentage and solid mass percentage were selected according to stepwise discriminant analysis.The accuracy of Bayes modes by using substitution method and cross validation method were 84.2% and 83.3%,respectively.Conclusion Solid volume percentage and solid mass percentage were important parameters for differentiating LPA from INV.Quantitative analysis of SSN was very helpful to preoperatively evaluate the subtypes and prognosis of lung adenocarcinoma by using 3DGCT segmentation technique.