Based on LC-MS technology explored the metabolomics of Agrimonia pilosa intervening in non-small cell lung cancer A549 cells / 药学学报

The objective of this study was to analyze the effects on cell viability, apoptosis, and cell cycle of non-small cell lung cancer (NSCLC) A549 cells after intervention with Agrimonia pilosa (AP) and investigate Agrimonia pilosa anti-tumor activity in vitro. Meanwhile, liquid chromatography mass spectrometry (LC-MS) metabolomics technology was used to analyze the changes of cellular metabolites and metabolic pathways. The results of this study will provide a theoretical and experimental basis for investigating the mechanism of the effect of Agrimonia pilosa on non-small cell lung cancer A549 cells. The results showed that the cell nucleus of A549 cells crumpled and apoptosis occurred with the increase of drug concentration. The survival rate of the cells decreased, and the inhibition rate reached 21.5% and 91.74% under the low and high dose conditions, respectively. Lactate dehydrogenase (LDH) content increased (P < 0.05). Metabolomics results showed significant differences in metabolism between groups, thirty-three distinct metabolites including LysoPC(24:0/0:0), LysoPC(17:0/0:0) and PC(O-40:5) were deduced. The pathway enrichment showed that the Agrimonia pilosa plays an anti-tumor role mainly by regulating the metabolism of glycerophosphate and purine in A549 cells, in which the effect on glycerophosphate metabolism pathway was most significant. The results of combined pharmacodynamics suggested that Agrimonia pilosa might induce apoptosis and inhibit the growth of A549 cells by regulating LysoPC(24:0/0:0), LysoPC(17:0/0:0) and PC(O-40:5) metabolites in A549 cells.

Neuroprotective effect and mechanism of celastrol and its derivatives in vitro / 中国药房

OBJECTIVE To explore the neuroprotective effect and possible mechanism of celastrol （Cel） and its derivatives （Cel-1， Cel-2） in terms of neuroinflammation and oxidative damage. METHODS Neuroinflammation model of microglial BV2 cells was induced by 1 μg/mL lipopolysaccharide （LPS）； oxidative damage model of human neuroblastoma SH-SY5Y cells was induced by 200 μmol/L hydrogen peroxide （H2O2）. The toxicity of different concentrations of Cel， Cel-1 and Cel-2 （0.625-20 μmol/L） to the two types of cells was investigated. The levels of nitric oxide （NO）， tumor necrosis factor α （TNF-α）， interleukin 1β （IL-1β）， and IL-6 in BV2 cells induced by LPS at safe concentrations （0.039-0.625 μmol/L） were all detected. The survival rate of SH-SY5Y cells induced by H2O2 was also determined. The expression levels of phosphoinositide 3-kinase （PI3K）， p-PI3K， protein kinase B （Akt）， p-Akt， cystatinase 3 （caspase-3）， B-cell lymphoma 2 （Bcl-2） and Bcl-2-related X protein （Bax） in SH- SY5Y cells induced by H2O2 at 0.156， 0.313， 0.625 μmol/L of active compound 2 were all detected. RESULTS In the concentration gradient range between 0.039 and 0.625 μmol/L， the results of neuroinflammation model experiments showed that Cel， Cel-1 and Cel-2 could reduce the contents of NO， TNF-α， IL-1β， and IL-6 in culture medium of BV2 cells （P＜0.05 or P＜ 0.01）； their IC50 values for neuroinflammation were （0.25±0.04）， （0.61±0.14） and （0.11±0.02） μmol/L respectively. Meanwhile， all of them could reverse the phenomenon of decreased cell survival rate after H2O2 treatment in the oxidative damage experiments at a certain concentration （P＜ 0.05 or P＜0.01）， with neuroprotective EC50 values of （0.43± XJC2023009） 0.08）， （0.45±0.04） and （0.28±0.03） μmol/L， respectively.Induced by H2O2， the phosphorylation of PI3K and Akt protein， protein expressions of Bcl-2 and Bcl-2/Bax ratio were all increased significantly （P＜0.05 or P＜0.01）， while the protein expressions of caspase-3 and Bax were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Cel， Cel-1， and Cel-2 all have significant neuroprotective activities at certain concentrations， and Cel-2 shows the most significant protective effect. The mechanism of action of Cel-2 may be related to regulating the PI3K/Akt and caspase-3/Bcl-2/Bax signaling pathways， reducing the inflammatory response， oxidative stress damage and inhibiting neuronal apoptosis.

Correlation between stool form and diversity of intestinal flora among children and adolescents / 中国学校卫生

Objective@#To investigate the differences and diversity changes in gut microbiota between children and adolescents with constipation and diarrhea, and healthy individuals, and to explore the correlation between changes in stool consistency and gut microbiota, in order to provide a scientific reference for the research on intestinal microecology among children and adolescents.@*Methods@#From October 2021 to March 2022, a total of 42 children and adolescents with constipation and 37 with diarrhea from a tertiary hospital in Hangzhou City, and 43 healthy individuals from 3 primary and secondary schools were included in this study. Fecal samples of children and adolescents were collected and then stool genomic DNA was extracted for 16S rRNA gene high throughput sequencing, and the sequencing results were analyzed. In the analysis of alpha diversity, the Kruskal-Wallis rank sum test was used to compare the differences between the three groups, and the FDR multiple testing correction was used for pairwise comparisons. In the analysis of beta diversity, the Adonis test was used to compare the overall differences between the three groups, and the ANOSIM test was used for pairwise comparisons. In the LEfSe analysis, the LDA scores obtained through LDA analysis (linear regression analysis).@*Results@#Alpha diversity analysis showed that there were statistically significant differences in the Shannon index (4.01, 3.81, 4.19) and Simpson index (0.05, 0.06, 0.04) between the diarrhea group, constipation group, and healthy group ( H=6.05, 6.35, P <0.1). Further pairwise comparison showed that the Shannon index and Simpson index of the healthy group were higher than those of the constipation group ( P <0.1). Beta diversity analysis showed that the impact of grouping factors on inter group differences was statistically significant ( R 2=0.045, P <0.1). Community composition analysis showed that there were 234 species in total among the three groups, and 36 unique species in the healthy group, 36 species in the diarrhea group, and 48 species in the constipation group. Species difference analysis showed significant differences in species composition at the genus level among the three groups ( H=0.000 05, 0.000 16, 0.000 20, 0.000 21, 0.000 53, 0.001 39, P <0.1), including Lachnospiraceae of Firmicutes phylum, Eubacterium hallii, Veillonellaceae, Qscillospiraceae, Butyricicoccaceae and Staphylococcaceae, respectively. KEGG abundance statistics and COG functional analysis showed that there were no significant differences in gene expression abundance of the same function among the three groups ( P >0.1).@*Conclusions@#The different stool consistency of children and adolescents is related to changes in gut microbiota composition. Compared to the healthy group, children with constipation or diarrhea have disrupted gut microbiota balance, with a shift in dominant bacteria and a higher abundance of opportunistic pathogens.

Genetically predicted waist circumference and risk of atrial fibrillation / 中华医学杂志(英文版)

INTRODUCTION@#Observational studies have revealed an association between waist circumference (WC) and atrial fibrillation (AF). However, it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk factors. Therefore, the causal role of WC in AF is unclear. This study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization (MR) analysis.@*METHODS@#In our two-sample MR analysis, the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study (GWAS) of WC (42 single nucleotide polymorphisms with a genetic significance of P <5 × 10 -8 ). The data of WC (from the Genetic Investigation of ANthropometric Traits consortium, containing 232,101 participants) and the data of AF (from the European Bioinformatics Institute database, containing 55,114 AF cases and 482,295 controls) were used to assess the causal role of WC on AF. Three different approaches (inverse variance weighted [IVW], MR-Egger, and weighted median regression) were used to ensure that our results more reliable.@*RESULTS@#All three MR analyses provided evidence of a positive causal association between high WC and AF. High WC was suggested to increase the risk of AF based on the IVW method (odds ratio [OR] = 1.43, 95% confidence interval [CI], 1.30-1.58, P = 2.51 × 10 -13 ). The results of MR-Egger and weighted median regression exhibited similar trends (MR-Egger OR = 1.40 [95% CI, 1.08-1.81], P = 1.61 × 10 -2 ; weighted median OR = 1.39 [95% CI, 1.21-1.61], P = 1.62 × 10 -6 ). MR-Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and AF.@*CONCLUSIONS@#Our findings suggest that greater WC is associated with an increased risk of AF. Taking measures to reduce WC may help prevent the occurrence of AF.

The efficacy of da Vinci robot-assisted lobectomy versus segmentectomy for stage ⅠA non-small cell lung cancer: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective    To compare and analyze the therapeutic effects of robot-assisted lobectomy and segmentectomy for stage ⅠA non-small cell lung cancer with a diameter≤2 cm. Methods    A total of 181 patients with pathologically confirmed stage ⅠA non-small cell lung cancer (diameter≤2 cm) who underwent robot-assisted lobectomy and segmentectomy in our hospital from 2018 to 2021 were included. There were 74 males and 107 females with an average age of 57.50±10.60 years. They were divided into two groups according to the surgical procedure: a segmentectomy group (85 patients) and a lobectomy group (96 patients). Results    There was no statistically significant  difference between the two groups in terms of clinical data such as age, gender, smoking history, basic disease, pathological type, tumour diameter, operative time, postoperative 24 h drainage volume and overall complications (P>0.05). The intraoperative blood loss (33.88±16.26 mL vs. 39.27±19.48 mL, P=0.046), groups of dissected lymph nodes (4.76±1.19 vs. 5.52±1.46, P=0.000), number of dissected lymph nodes (14.81±7.23 vs. 18.06±7.70, P=0.004) and postoperative 72 h drainage volume (561.65±225.31 mL vs. 649.84±324.34 mL, P=0.037) of patients in the segmentectomy were less than those in the lobectomy group. The chest drainage time (5.49±3.92 d vs. 7.60±4.96 d, P=0.002) and postoperative hospital stay time (7.47±4.16 d vs. 9.67±5.50 d, P=0.003) were shorter than those in the lobectomy group. There was no conversion to thoracotomy or perioperative death in the two groups. The postoperative follow-up rate was 100.0% with a longest follow-up time of 48 months. The 3-year recurrence-free survival rates of the segmentectomy group and lobectomy group were 87.7% and 92.4%, respectively (P=0.465). Conclusion    The da Vinci robot-assisted lobectomy and segmentectomy are safe and feasible surgical procedures for patients with stage ⅠA non-small cell lung cancer (diameter≤2 cm), with a similar 3-year recurrence-free survival rate. The lobectomy group has more lymph nodes dissected, while the segmentectomy group is superior to the lobectomy group in terms of intraoperative blood loss, postoperative 72 h chest drainage volume, chest drainage time and postoperative hospitalization time.

Effectss of hyperoside on traumatic brain injury rats by regulating RhoA/ROCK signaling pathway / 中国临床药理学与治疗学

AIM: To investigate the effects of hyperoside on traumatic brain injury (TBI) rats by regulating the Ras homolog gene family, member A (RhoA)/Rho-associated coiled coil-forming kinase (ROCK) signal pathway. METHODS: The TBI rat model was established by modified Feeney free fall hit method, and was randomly divided into model group, low-dose hyperoside (60 mg / kg) group, high-dose hyperoside (120 mg / kg) group, high-dose hyperoside (120 mg / kg) + no load group, and high-dose hyperoside (120 mg / kg) + RhoA overexpression group, with 10 rats in each group, another 10 healthy rats were set as sham operation group, after hyperoside and plasmid were grouped, the nerve injury was detected by modified neurological deficit score (mNSS) and dark avoidance test; Evans blue (EB) quantitative method was used to detect the permeability of blood brain barrier in rats; ultrastructural damage of blood-brain barrier was observed by transmission electron microscopy; the levels of tumor necrosis factor- α (TNF- α), interleukin-8 (IL-8), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and brain tissue of rats were measured with the kit; and the expression of RhoA/ROCK pathway related proteins in rat brain was detected by Western blot. RESULTS: Compared with the sham operation group, the blood brain barrier structure of the model group rats was damaged, the step-through latency and SOD level decreased obviously (P0.05). CONCLUSION: Hyperoside can inhibit neuroinflammation and oxidative stress in TBI rats by down-regulating RhoA / ROCK signal pathway, thereby reducing the damage of blood brain barrier and repairing its neural function.

Potential targets and mechanism of Houpuwenzhongtang for the treatment of spleen and stomach deficiency cold stomach disease based on network pharmacology / 中国药理学通报

Aim To explore the potential targets and mechanisms of Houpuwenzhongtang for the treatment of spleen and stomach deficiency cold stomach disease. Methods Firstly, TCMSP database, disease database and compound target prediction platform were used to collect active components, disease targets and predict potential targets. Secondly, Cytoscape 3.7.2 and String platform were used to screen key chemical components and core targets, and PPI network diagram was constructed. Finally, The active components with degree greater than 30 were used for molecular docking with key targets, and some docking results were selected for cell experiment. Results The key active components of Houpuwenzhongtang in the treatment of spleen and stomach deficiency cold stomach disease were hesperidin, magnolol, 6-gingerol, and so on. The key targets were JUN, AKT1, IL-8, etc.. The related pathways mainly involved immune response, signaling transduction, cell proliferation and apoptosis. Molecular docking results showed that the key active components had good binding activity with disease targets. The results of cell experiments showed that magnolol, hesperidin and 6-gingerol had different degrees of anti-inflammatory activity against IL-8 in a dose-dependent manner. Conclusions It is speculated that Houpuwenzhongtang may act on IL-8, JUN, AKT1 and other targets through magnolol, hesperidin,6-gingerol and other active ingredients, and participate in the regulation of PI3K-AKT signaling pathway, N F-K B signaling pathway for the treatment of spleen and stomach deficiency cold stomach disease. And it is found for the first time that 6-gingerol could stably bind to multiple disease targets related spleen and stomach deficiency cold stomach disease,such as AKT1,IL-8 and so on. The result suggests that 6-gingerol is worth further research. Through the results of IL-8 cell experiment, it is speculated that the components such as magnolol and hesperidin may play a role in gastric diseases caused by Helicobacter pylori infection by reducing the content of IL-8 in gastric mucosa.

Clinical and molecular biological characterization of patients with accelerated chronic lymphocytic leukemia / 中华血液学杂志

Objective: To investigate the clinical and molecular biological characteristics of patients with accelerated chronic lymphocytic leukemia (aCLL) . Methods: From January 2020 to October 2022, the data of 13 patients diagnosed with aCLL at The First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed to explore the clinical and molecular biological characteristics of aCLL. Results: The median age of the patients was 54 (35-72) years. Prior to aCLL, five patients received no treatment for CLL/small lymphocytic lymphoma (SLL), while the other patients received treatment, predominantly with BTK inhibitors. The patients were diagnosed with aCLL through pathological confirmation upon disease progression. Six patients exhibited bulky disease (lesions with a maximum diameter ≥5 cm). Positron emission tomography (PET) -computed tomography (CT) images revealed metabolic heterogeneity, both between and within lesions, and the median maximum standardized uptake value (SUVmax) of the lesion with the most elevated metabolic activity was 6.96 (2.51-11.90). Patients with unmutated IGHV CLL accounted for 76.9% (10/13), and the most frequent genetic and molecular aberrations included +12 [3/7 (42.9% ) ], ATM mutation [6/12 (50% ) ], and NOTCH1 mutation [6/12 (50% ) ]. Twelve patients received subsequent treatment. The overall response rate was 91.7%, and the complete response rate was 58.3%. Five patients experienced disease progression, among which two patients developed Richter transformation. Patients with aCLL with KRAS mutation had worse progression-free survival (7.0 month vs 26.3 months, P=0.015) . Conclusion: Patients with aCLL exhibited a clinically aggressive course, often accompanied by unfavorable prognostic factors, including unmutated IGHV, +12, ATM mutation, and NOTCH1 mutation. Patients with CLL/SLL with clinical suspicion of disease progression, especially those with bulky disease and PET-CT SUVmax ≥5, should undergo biopsy at the site of highest metabolic uptake to establish a definitive pathological diagnosis.

Current status and outlook of medical treatment for KRAS-mutated non-small cell lung cancer / 中华肿瘤杂志

Lung cancer remains the leading cause of cancer-related deaths in men and women worldwide, and 85% of these patients have non-small cell lung cancer. In recent years, the clinical use of targeted drug therapy and immune checkpoint inhibitors has dramatically changed the treatment landscape for advanced NSCLC. The mechanism and the value of targeted therapies have been a hot topic of research, as KRAS is one of the earliest discovered and most frequently mutated oncogenes, which is activated by binding to GTP and triggers a series of cascade reactions in cell proliferation and mitosis. The KRAS protein acts as a molecular switch and is activated by binding to GTP, triggering a series of cascade responses in cell proliferation and mitosis. Clinically, patients with KRAS mutated NSCLC have poor response to systemic medical therapy and poor prognosis. Since the first report of KRAS gene in 1982, research on KRAS targeted therapeutics has been slow, and previous studies such as farnesyltransferase inhibitors and downstream protein inhibitors of KRAS signaling pathway have not achieved the expected results, making KRAS long defined as a "non-druggable target". The deeper understanding of the crystal structure of KRAS has led to the discovery of potential therapeutic sites for KRAS and the development of several drugs directly targeting KRAS, especially KRAS G12C inhibitors such as AMG510 (sotorasib) and MRTX849 (adagrasib), which have shown encouraging results in clinical trials. In recent years, studies on the therapeutic efficacy of immune checkpoint inhibitors for KRAS-mutated NSCLC have made some progress. In this review, we systematically introduce the basic understanding of RAS gene and clinical characteristics of KRAS mutated NSCLC patients, summarize the medical treatments for KRAS mutated NSCLC, including chemotherapy, anti-vascular drug therapy and tumor immunotherapy, and focus on the review and outlook of the research progress of KRAS targeted therapy.

Application of Modified Intraoperative Axillary Fluoroscopy for Posterior Acromioclavicular Joint Dislocation / 中山大学学报(医学科学版)

ObjectiveThe study aims to determine whether the horizontal posterior displacement of the distal clavicle in patients with acromioclavicular joint dislocation can be corrected via the application of modified intraoperative axillary fluoroscopy. MethodsFrom February 2019 to April 2021， 50 patients with Rockwood type Ⅲ acromioclavicular joint dislocation eligible for inclusion were randomly divided into two groups： the normal （32 cases） and the experimental （18 cases）. The conventional anteroposterior position radiographs were obtained to detect the surgery effect on the patients in the normal group. In experimental group， modified intraoperative axillary radiographs were obtained， with the concept of polar coordinates introduced to reduce the horizontal posterior translation of the clavicle. Then we compared the perioperative parameters， such as average operative time， intraoperative blood loss between the two groups. The Constant score was used for assessing the postoperative function of the shoulder joint in the follow-up visits. ResultsNo statistically significant difference was found in gender， age， duration of injury， underlying diseases， intraoperative blood loss and operative time between the two groups. The postoperative shoulder function score of the experimental group was higher than that of the normal group. ConclusionsThe application of modified intraoperative axillary fluoroscopy is recommendable for accurately reducing posterior translation of the distal clavicle， and meanwhile helpful for the precise placement of the clavicular plate.

Co-load of silybin and doxorubicin by MoS2 nanosheets for synergetic chemotherapy and photothermal therapy of lung cancer / 药学学报

The active ingredient of traditional Chinese medicine, silybin (SBN), can inhibit the proliferation of cancer cells and enhance the anticancer effect of doxorubicin (DOX). However, due to non-targeting and short half-life of SBN and DOX, as well as different administration routes and pharmacokinetic processes, this combination drug cannot act on the tumor in the set order, seriously eliminating the synergistic effect between them and limiting the effect in vivo. Therefore, we intended to construct a nano-delivery system based on molybdenum disulfide (MoS2), modified by polyethylene glycol (PEG) and sialic acid (SA), and co-loaded with SBN and DOX. The system induced the release of combined drugs under the dual-stimulation of pH and near infra-red (NIR), increased the free concentration of intracellular drugs, so as to achieve the synergistic effect between them. The animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Fujian University of Traditional Chinese Medicine. MoS2-PEG-SA-SBN/DOX circulated in vivo, and effectively accumulated at tumor sites through enhanced permeability and retention effect (EPR) and SA-mediated active targeting. Under near infrared light irradiation, MoS2-PEG-SA-SBN/DOX realized the combination of synergistic chemotherapy and photothermal therapy for tumor, thus achieving excellent anti-tumor effect in vivo. This study can provide a new idea and strategy for the clinical treatment of lung cancer. Taken together, MoS2-PEG-SA-SBN/DOX can offer a new idea and strategy for the clinical treatment of lung cancer.

Effect of sodium fluoride on myocardial damage by regulating apoptosis through JNK signaling pathway / 环境与职业医学

Background It has been found that fluoride may cause cardiomyocyte damage. c-Jun N-terminal kinases (JNK) signaling pathway plays an important role in apoptosis, but its role in fluorosis-induced cardiomyocyte damage is still unknown yet. Objective To explore the toxic effect of sodium fluoride (NaF) on H9c2 cardiomyocytes of rats and whether NaF affects cardiomyocyte apoptosis through the JNK signaling pathway. Methods According to the concentrations of sodium fluoride and whether sp600125 (JNK inhibitor) was added, cardiomyocytes of rats were divided into six groups, including control group, SP600125 group (SP group), 0.24, 0.48, and 0.96 mmol·L−1 NaF groups, and 0.96 mmol·L−1 NaF+SP600125 group (NaF+SP group). Cardiomyocytes exposed to NaF for 24 h were observed using a fluorescence inverted microscope. The changes of cell viability at 24, 48, and 72 h after the treatment were detected by CCK-8 method. The levels of reactive oxygen species (ROS) at 24 h after the treatment in H9c2 cardiomyocytes were determined by fluorescent probe method. The expression levels of Bcl-2, Bax, Caspase-3, and JNK mRNA at 24 h after the treatment were detected by real-time PCR. The protein expression levels of Bcl-2, Bax, Caspase-3, and p-JNK at 24 h after the treatment were detected by Western blotting. Results Compared with the control group, after being exposed to 0.48 and 0.96 mmol·L−1 NaF for 24 h, the cell growth density decreased. With the increase of NaF concentration, rounded cells and some suspended dead cells appeared. At 24h after exposure to NaF, the cell viability of the 0.48 and 0.96 mmol·L−1 NaF groups decreased compared with the control group (P<0.05). At 48h and 72h after exposure to NaF, the cell viability levels of the NaF treated groups were significantly lower than that of the control group (P<0.05). After NaF exposure for 24 h, compared with the control group, the intracellular ROS levels were increased (P<0.05); the mRNA expression levels of Bcl-2 were decreased to varying degrees, especially in the 0.48 and 0.96 mmol·L−1 NaF groups (P<0.05); the mRNA expression levels of Bax, Caspase-3, and JNK were increased (P<0.05); the protein expression levels of Bcl-2 were reduced (P<0.05); the protein expression levels of Bax, Caspase-3, and p-JNK were elevated (P<0.05). Compared with the 0.96 mmol·L−1 NaF group, the cell viability of the NaF+SP group was increased, the intracellular ROS level was decreased, the mRNA expression levels of Bax, Caspase-3, and JNK were decreased, the protein expression level of Bcl-2 was increased, and the protein expression levels of Bax, Caspase-3, and p-JNK were decreased (P<0.05); the expression level of Bcl-2 mRNA had a rising trend but showed no statistical significance (P>0.05). Conclusion Cardiomyocyte damage after excessive fluoride exposure may result from fluoride inducing excessive ROS production in cardiomyocytes, which may activate the JNK signaling pathway and induce cardiomyocyte apoptosis.

Development and Application of Ontology of Cancer Hallmarks / 中国医学科学院学报

Objective To develop a traceable cancer hallmark ontology with terminology including gene mutation,cancer hallmark,and cell line for knowledge integration,standardization,correlation,and discovery.Methods The Ontology Development 101 and the current ontology development methods were employed to determine the content coverage,structural layers,reusable terms,and new terms of the cancer hallmark ontology.Taking colorectal cancer as a study case,we extracted the knowledge related with colorectal cancer hallmarks using text mining and text classification technology from PubMed,and then formalized the extracted knowledge into the cancer hallmark ontology.Moreover,we made use of existing cancer hallmark evidence in Catalogue of Somatic Mutations in Cancer and further semantic retrieval to discover new knowledge.Results The established cancer hallmark ontology comprised 9910 classes and 6138 instances,which realized the semantic representation of 2310 article abstracts about colorectal cancer and 26 pieces of evidence about genes and their cancer hallmarks.Compared with the Catalogue of Somatic Mutations in Cancer,new evidence for more genes associated with colorectal cancer hallmarks was found based on cancer hallmark ontology.Conclusion This study is of great significance to the research on the cancer pathogenesis at the molecular level,the revealing of specific roles of genes and mutations in the occurrence of cancer,and the rapid knowledge discovery of cancer hallmarks.

Manifestations and distribution rules of jingjin lesions in neck-type cervical spondylosis / 中国针灸

OBJECTIVE@#To explore the manifestations of jingjin (sinews/fascia) lesions and summarize their distribution rules in the patients with neck-type cervical spondylosis so as to provide the evidences for the development of clinical diagnosis and treatment scheme of acupuncture for cervical spondylosis.@*METHODS@#A total of 120 patients with neck-type cervical spondylosis were collected. The meridian diagnostic method was used to examine the upper back of each patient, the manifestation category of jingjin lesions, locations and the affected muscle regions of twelve meridians were recorded.@*RESULTS@#(1) The punctate lesions of jingjin were detected in 15 regions, and the highest frequency of lesion occurred in the region from the inner upper corner of the scapula to Quyuan (SI 13) (113 cases, 94.2% of lesion frequency). The lesion frequency of 10 regions was ≥50.0%. The punctate lesions were mainly distributed in the muscle regions of hand-shaoyang (349 cases) and foot-taiyang (333 cases). (2) The linear lesions of jingjin were detected in 10 regions, and the highest frequency of lesion occurred in the region from the inner upper corner of the scapula to Quyuan (SI 13) (77 cases, 64.2% of lesion frequency). The lesion frequency of 2 regions was ≥50.0%. The linear lesions occurred mainly in the muscle region of foot-taiyang (251 cases). (3) Eight regions were examined to be the planar lesions of jingjin, and the highest frequency of lesion was found in the site of Jianjing (GB 21) (84 cases, 70.0% of lesion frequency). The lesion frequency of 3 regions was ≥50.0%. The muscle region of foot-taiyang (260 cases) was predominated in the planar lesions. (4) The distribution of all of the punctate, linear and planar lesions of jingjin was analyzed statistically. It was found that 25 regions were involved and those with the high lesion frequency were distributed in the area from the inner upper corner of the scapula to Quyuan (SI 13), the sites of Jianjing (GB 21) and Dazhui (GV 14), transverse processes of C3 to C5 and the area from the lateral border of the scapula to the teres minor, separately. The muscle regions of foot-taiyang, hand-shaoyang and hand-yangming were involved in various kinds of jingjin lesions.@*CONCLUSION@#Jingjin lesions in patients with neck-type cervical spondylosis can be divided into three categories, namely, punctate, linear and planar lesions; of which, the punctate lesions are dominated. A majority of jingjin lesions is related to the muscle region of foot-taiyang, and the lesion frequency is higher compared with the lesions to the muscle regions of hand-shaoyang and hand-yangming. Jingjin lesions are commonly distributed in the area from the inner upper corner of the scapula to Quyuan (SI 13).

Analysis on the Exemplary Role of Medical Youth in Public Health Emergencies / 中国医学伦理学

In recent years, due to the complex international situation, frequent outbreaks of public health emergencies, and the rapid development of various new media, negative emotions and various rumors often spread at an extremely fast speed within certain groups, and increase in geometric multiples. Medical youth, as young talents with medical professional knowledge, have a certain influence, and can adapt to the development of various new things in the new era and timely respond to various emergencies. They are also the backbone of various departments in hospitals in emergencies, especially public health emergencies. Therefore, combining the actual situation with on-site investigation to analyze the role model and exemplary role played by medical youth in public health emergencies, and further summarize and amplify this exemplary and pioneering role of medical youth through analysis and research, has important practical significance for fully exerting their positive role in such events.

Da Vinci robotic versus thoracoscopic surgery via subxiphoid approach for treatment of anterior mediastinal tumor: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective     To compare the effects of anterior mediastinal tumor resection by the Da Vinci robot and video-assisted thoracoscopy via subxiphoid approach. Methods     A retrospective cohort study was conducted to continuously enroll patients who underwent anterior mediastinal tumor resection between 2020 and 2021 in our department. They were divided into a robotic group and a subxiphoid thoracoscopic group. The differences of general indexes (intraoperative blood loss, postoperative drainage volume, postoperative catheterization time, postoperative hospital stay), postoperative pain visual analogue scale (VAS), perioperative declining levels of hemoglobin, hematocrit, serum prealbumin and serum albumin were compared and analyzed. Results     A total of 113 patients were enrolled. There were 76 patients in the robotic group (46 males and 30 females, median age of 50 years) and 37 patients in the subxiphoid thoracoscopic group (21 males and 16 females, median age of 51 years). Intraoperative blood loss, postoperative drainage volume, postoperative catheterization time and postoperative hospital stay of the robotic group were better than those in the subxiphoid thoracoscopic group (P<0.05). The postoperative VAS scores in the robotic group were lower than those in the subxiphoid thoracoscopic group, but there was no statistical difference (P>0.05). Perioperative declining levels of hemoglobin, and hematocrit were not statistically different between the two groups (P>0.05). Declining levels of serum prealbumin, and serum albumin in the robotic group were lower than those in the subxiphoid thoracoscopic group (P<0.05). Conclusion     Da Vinci robotic and subxiphoid video-assisted thoracoscopic surgeries for the treatment of anterior mediastinal tumors are both safe and reliable, with short postoperative hospital stay, mild postoperative pain and quick recovery. Da Vinci robot surgery has a slight advantage in the treatment outcome.

Analysis of the current situation and countermeasures of pediatric drug procurement in China under the background of centralized drug procurement / 中国药房

OBJECTIVE To analyze the current situation of pediatric drug use under centralized drug procurement， and to provide reference for the subsequent design of pediatric drug centralized procurement rules. METHODS The comparative analysis method was used to analyze the problems in the centralized procurement， clinical use and supply of pediatric drugs from the aspects of centralized procurement selection results and actual use of pediatric drugs， price difference and online prices of pediatric drugs. The solutions were put forward to optimize the centralized procurement and pricing rules of pediatric drugs. RESULTS & CONCLUSIONS The demands for pediatric drugs in China were increasing， but the supply of marketed pediatric drugs was insufficient （including insufficient coverage of disease fields， insufficient varieties， insufficient suitable dosage forms for children， insufficient specifications for children， etc.）， and the development of pediatric drugs was relatively difficult. After merging the dosage forms of centralized procurement according to the medical insurance list， some suitable dosage forms and specifications for children couldn’t be selected， resulting in a shortage of clinical pediatric medication. Relevant enterprises’ enthusiasm for developing and producing pediatric drugs and participating in online competitions had decreased. There was also the problem of underpricing of pediatric drugs under the drug price difference ratio rule. It is recommended that when conducting centralized drug procurement， special drugs for children should be grouped separately for centralized procurement based on attributes and the population covered by the indications. The specifications of suitable pediatric drugs that were not selected are converted into the agreed purchase quantity of medical institutions in a certain proportion. It is necessary to further optimize the pricing rules for pediatric specialized drugs， ensure a certain profit margin for such drugs， increase the willingness of production enterprises to research， develop and supply drugs， and thus ensure the use and supply of pediatric drugs.

Advances in immune checkpoint inhibitors combined with other treatments / 中国药科大学学报

@#As one of the most attention-attracting immunotherapy, immune checkpoint inhibitors (ICIs) have been approved as the first-line drugs for the therapy of various types of cancers.Nevertheless, the single application of ICIs exhibited limited efficacy, and it is easy to develop drug resistance.Therefore, the development of combination therapies become a hot topic in this field to improve the efficacy of ICIs therapy.This article describes some new ICIs targets, reveals the mechanisms of resistance, and introduces the current status of combination other therapies with ICIs therapy systematically including chemotherapy, radiotherapy, hyperthermia, antiangiogenic therapy, tumor vaccines, cytokine therapy and adoptive cellular therapy.Furthermore, the synergistic mechanism of combination therapy to enhance antitumor effect.Thus, this article provides solid references for personalized combination therapy according to the pathological characteristics of patients.

"Leverage pry-off method" for effective prevention of thermal injury during microwave ablation of benign thyroid nodules / 南方医科大学学报

OBJECTIVE@#To assess the safety and efficacy of"leverage pry-off method"for preventing thermal injury during microwave ablation of benign thyroid nodules.@*METHODS@#From July, 2017 to September, 2019, a total of 348 patients with benign thyroid nodules underwent ultrasound-guided microwave ablation. For protecting from thermal injury during the ablation, "hydrodissection technique" was used in 174 of the patients (admitted from July, 2017 to August, 2018) and "leverage pry-off method" in the other 174 patients (admitted from September, 2018 to September, 2019). All the patients were followed up for 1 to 12 months after the operation for observation of severe complications and nodular residues.@*RESULTS@#Ultrasound-guided microwave ablation was completed in all the 348 patients. The most common severe complication associated with the ablation was voice change, occurring in 3 cases (1.7%) in "hydrodissection technique" group and in 4 (2.3%) in the "leverage pry-off method" group, showing no significant difference between the two groups (P>0.05). During the follow-up, no significant difference was found in the rate of nodular residues between the "hydrodissection technique" group and "hydrodissection technique" group (9.8% vs 10.9% (P>0.05).@*CONCLUSIONS@#The "leverage pry-off method" is simple and effective for preventing thermal injury during microwave ablation of benign thyroid nodules.

Clonotypic analysis of immunoglobulin heavy chain sequences among 44 patients with Waldenström macroglobulinemia / 中华医学遗传学杂志

OBJECTIVE@#To analyze the correlation between the mutational status of immunoglobulin heavy chain variable (IGHV) gene with the prognosis of patients with Waldenström macroglobulinemia (WM).@*METHODS@#Immunoglobulin heavy chain gene (IGH) clonotypic sequence analysis was carried out to assess the mutational status of IGHV in the blood and/or bone marrow samples from 44 WM patients. The usage characteristics of IGHV-IGHD-IGHJ gene was explored.@*RESULTS@#The most common IGHV subgroup was IGHV3, which was similar to the data from the Institute of Hematology of Chinese Academy of Medical Science. IGHV3-23 (20.45% vs. 15.44%) and IGHV3-74 (11.36% vs. 7.35%) were the main fragments used, which was followed by IGHV4 gene family (15.91% vs. 24.26%). However, no significant correlation was found between the IGHV4 usage and the prognosis of the patients. Should 98% be taken as the cut-off value for the IGHV mutation status, only 5 patients had no IGHV variant, and there was no correlation with the prognosis. Based on the X-tile analysis, 92.6% was re-selected as the cut-off value for the IGHV variant status in such patients. LDH was increased in 26 patients (59.1%) without IGHV variant (P < 0.05), whilst progression-free survival (P < 0.05) and overall survival (P < 0.05) were significantly shorter compared with those with IGHV variants.@*CONCLUSION@#The usage characteristics of IGHV-IGHD-IGHJ in our patients was similar to reported by the Institute of Hematology of Chinese Academy of Medical Science, albeit that no correlation was found between the IGHV4 usage and the prognosis of the patients. Furthermore, 98% may not be appropriate for distinguishing the IGHV variant status in WM patients.