Research Progress in Preoperative Evaluation of Lymph Node Metastasis of Bladder Cancer / 中国医学科学院学报

Bladder cancer is a common malignant tumor of the urinary system.The prognosis of patients with positive lymph nodes is worse than that of patients with negative lymph nodes.An accurate assessment of preoperative lymph node statushelps to make treatmentdecisions,such as the extent of pelvic lymphadenectomy and the use of neoadjuvant chemotherapy.Imaging examination and pathological examination are the primary methods used to assess the lymph node status of bladder cancer patients before surgery.However,these methods have low sensitivity and may lead to inaccuate staging of patients.We reviewed the research progress and made an outlook on the application of clinical diagnosis,imaging techniques,radiomics,and genomics in the preoperative evaluation of lymph node metastasis in bladder cancer patients at different stages.

Advances of immunotherapy-related biomarker in esophageal carcinoma / 中华胃肠外科杂志

Esophageal carcinoma is one of the most common malignant tumors in the world, with incidence and mortality rankings of 7th and 6th, respectively. In recent years, immunotherapy represented by immune checkpoint inhibitors of programmed death-1 and programmed death ligand 1 (PD-L1) has been introduced into clinical practice and has changed the treatment status of esophageal cancer. Although immunotherapy has provided long-term survival benefits for patients with advanced esophageal cancer and high pathological response rates in the neoadjuvant therapy, only a few of the patients have satisfactory therapeutic outcomes. Therefore, effective biomarkers for predicting immunotherapeutic effects are urgently needed to identify those patients who could benefit from immunotherapy. In this paper, we mainly discuss recent research advances of biomarkers related to the immunotherapy of esophageal cancer and the clinical application prospects of these biomarkers.

Optimization of perioperative treatment strategies for locally advanced esophageal squamous cell carcinoma from the perspective of tumor heterogeneity / 中华胃肠外科杂志

Recent advances in multimodality treatment offer excellent opportunities to rethink the paradigm of perioperative management for locally advanced esophageal squamous cell carcinoma. One treatment clearly doesn't fit all in terms of a broad disease spectrum. Individualized treatment of local control of bulky primary tumor burden (advanced T stage) or systemic control of nodal metastatic tumor burden (advanced N stage) is essential. Given that clinically applicable predictive biomarkers are still awaited, therapy selection guided by diverse phenotypes of tumor burden (T vs. N) is promising. Potential challenges regarding the use of immunotherapy may also boost this novel strategy in the future.

Establishment and validation of a nomogram-based predictive model for idiopathic aldosteronism / 中华内科杂志

Objective: To establish and validate a nomogram-based predictive model for idiopathic hyperaldosteronism (IHA). Methods: This cross-sectional study was conducted with the collected clinical and biochemical data of patients with primary aldosteronism (PA) including 249 patients with unilateral primary aldosteronism (UPA) and 107 patients with IHA, who were treated at the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to November 2022. Plasma aldosterone concentration (PAC) and plasma renin concentration (PRC) were measured by chemiluminescence. Stepwise regression analysis was applied to select the key predictors of IHA, and a nomogram-based scoring model was developed. The model was validated in another external independent cohort of patients with PA including 62 patients with UPA and 43 patients with IHA, who were diagnosed at the Department of Endocrinology, First Affiliated Hospital of Zhengzhou University. An independent-sample t test, Mann-Whitney U test, and χ2 test were used for statistical analysis. Results: In the training cohort, in comparison with the UPA group, the IHA group showed a higher serum potassium level [M(Q1, Q3), 3.4 (3.1, 3.8) mmol/L vs. 2.7 (2.1, 3.1) mmol/L] and higher PRC [4.0 (2.1, 8.2) mU/L vs. 1.5 (0.6, 3.4) mU/L] and a lower PAC post-saline infusion test (SIT) [305 (222, 416) pmol/L vs. 720 (443, 1 136) pmol/L] and a lower rate of unilateral adrenal nodules [33.6% (36/107) vs. 81.1% (202/249)]; the intergroup differences in these measurements were statistically significant (all P<0.001). Serum potassium level, PRC, PAC post-SIT, and the rate of unilateral adrenal nodules showed similar performance in the IHA group in the validation cohort. After stepwise regression analysis for all significant variables in the training cohort, a scoring model based on a nomogram was constructed, and the predictive parameters included the rate of unilateral adrenal nodules, serum potassium concentration, PAC post-SIT, and PRC in the standing position. When the total score was ≥14, the model showed a sensitivity of 0.65 and specificity of 0.90 in the training cohort and a sensitivity of 0.56 and specificity of 1.00 in the validation cohort. Conclusion: The nomogram was used to successfully develop a model for prediction of IHA that could facilitate selection of patients with IHA who required medication directly.

Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center / 中华血液学杂志

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.

Clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm accelerated/blast phase / 中华血液学杂志

Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.

The non-communicating intracranial-extracranial Rosai-Dorfman disease: a case report / 中华神经科杂志

Rosai-Dorfman disease (RDD) is a benign self-limited disease characterized by lymphadenopathy and phagocytosis of lymphocytes by histiocytes. A case of intracranial-extracranial non communicating RDD was reported in this paper. The patient was admitted to Shiyan Taihe Hospital in May 2020 because of "the left top scalp tumor was found for 4 months, and the right lower limb was numb for more than half a month". The plain scan and enhanced scan of the patient′s head magnetic resonance imaging (MRI) showed that the disease focus of the left parietal bone was slightly uneven enhanced, its internal and external soft tissues were significantly enhanced, and the local internal and external soft tissues were significantly thickened irregularly, with the size of about 3.2 cm× 4.7 cm, and adjacent brain parenchyma was compressed. After resection of left top mass and intracranial mass, pathological results showed spindle cell proliferation with inflammatory reaction, and immunohistochemical staining results supported the diagnosis of RDD. The neurological function of the patient recovered to normal basically 7 months after operation, and no recurrence of the disease was found in the MRI examination of the head. The treatment effect was satisfactory.

The Role of miR-21 in Skin-related Diseases and Wound Healing / 中国生物化学与分子生物学报

microRNA-21(miR-21) is an endogenous non-coding RNA and plays a key regulatory role in the process of cell proliferation and differentiation. In recent years, miR-21, as a widely studied miRNA, has attracted much attention for its role in skin- related diseases and wound healing. The study shows that miR-21, as a " broad factor", affects the proliferation, apoptosis, migration and invasion of different cells (keratinocytes, T cells, fibroblasts, etc.) by inhibiting the transcription and translation of different target genes (PTEN, TIMP, PDCD4, etc.) . At the same time, it plays a crucial role in skin tumors, skin immune diseases, skin inflammatory diseases, skin wounds and scar tissue formation by promoting inflammation through different signaling pathways. In this study, we reviewed the regulatory roles of miR-21 in different skin diseases (melanoma, cutaneous squamous cell carcinoma, T-cell lymphoma, psoriasis, scleroderma, etc.) and wound healing, aiming at deepening the understanding of miR-21 molecule in skin-related diseases and wound healing. The potential of miR-21 as a biomarker for skin disease diagnosis and its ability to evaluate the efficacy of drugs were also discussed. miR-21 is expected to become a new target of skin disease and wound healing, which may provide a new direction for clinical research.

Biological Implication of Chimeric RNAs in Cancer / 中国生物化学与分子生物学报

Chimeric RNA is a fusion transcript composed of exons from two or more different genes and generated by chromosome rearrangement or RNA splicing. Chimeric RNAs have the potential to encode novel proteins or function as non-coding RNAs. Chimeric RNAs were ubiquitously expressed across different cancers and normal tissues. To date, mechanistic and functional studies of chimeric RNAs still remain unclear. Precise definition and terminology in the research field of chimeric RNA will be discussed in this review. The formation, classification and clinical significance of chimeric RNAs in cancer progression will be summarized. Previous studies showed that products of chimeric RNAs may play important roles in regulating cell proliferation, motility, invasion and apoptosis through encoded fusion proteins or long non-coding chimeric RNAs. In cancer, chimeric RNA and its encoded specific protein or non-coding RNA can regulate tumorigenesis by changing cell phenotypes or directly affecting gene expression or regulatory pathways, which have the potential to be important diagnostic biomarkers and therapeutic targets. In recent years, more and more cancer-specific chimeric RNAs have been discovered from multiple types of cancers and used as therapeutic targets due to their vital roles in disease prognosis. Therefore, this review will focus on the functions and applications of chimeric RNAs in different tumors, which can shed a light on cancer diagnosis and therapeutics from the new perspective.

Clinical and laboratory features compared between JAK2 exon12 and JAK2 V617F mutated polycythemia vera / 中华血液学杂志

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.

Chemical synthesis of a synthetically useful L-galactosaminuronic acid building block / 中国天然药物

Most bacterial cell surface glycans are structurally unique, and have been considered as ideal target molecules for the developments of detection and diagnosis techniques, as well as vaccines. Chemical synthesis has been a promising approach to prepare well-defined oligosaccharides, facilitating the structure-activity relationship exploration and biomedical applications of bacterial glycans. L-Galactosaminuronic acid is a rare sugar that has been only found in cell surface glycans of gram-negative bacteria. Here, an orthogonally protected L-galactosaminuronic acid building block was designed and chemically synthesized. A synthetic strategy based on glycal addition and TEMPO/BAIB-mediated C6 oxidation served well for the transformation of commercial L-galactose to the corresponding L-galactosaminuronic acid. Notably, the C6 oxidation of the allyl glycoside was more efficient than that of the selenoglycoside. In addition, a balance between the formation of allyl glycoside and the recovery of selenoglycoside was essential to improve efficiency of the NIS/TfOH-catalyzed allylation. This synthetically useful L-galactosaminuronic acid building block will provide a basis for the syntheses of complex bacterial glycans.

Effect of Wenshen Yangxue Prescription on Outcome of In Vitro Fertilization- embryo Transfer in Patients with Poor Ovarian Response / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of Wenshen Yangxue prescription （WSYX） on the outcome of in vitro fertilization-embryo transfer （IVF-ET） in poor ovarian responders and the safety. MethodA total of 116 eligible patients who were admitted to Beijing Obstetrics and Gynecology Hospital in June 2016-June 2019 were randomized into the experimental group and the control group with random number table method （58 in either group）. Conventional controlled ovarian hyperstimulation （COH） was directly implemented in the control group， while the experimental group was intervened with WSYX for 3 menstrual cycles before the COH. The pregnant patients were observed till childbirth and the non-pregnant patients for 12 months. Gonadotropins （Gn） dosage and the days of use were recorded. Serum levels of follicle-stimulating hormone （FSH）， basal FSH （bFSH）， basal luteinizing hormone （bLH）， and basal estrogen （bE2）， endometrial thickness， and antral follicle count （AFC） before and after treatment were measured. The serum levels of estrogen （E2）， progesterone （P）， and luteinizing hormone （LH） on the day of human chorionic gonadotropin （HCG） injection， and levels of FSH， LH， E2， testosterone （T）， and P in follicular fluid 36 h after HCG injection were determined. Number of fertilization， rate of fertilization， number of high-quality embryos， cycle cancellation rate， clinical pregnancy rate， and live birth rate were evaluated. The traditional Chinese medicine （TCM） syndrome scores before and after treatment were recorded. Liver and kidney functions were detected before and after treatment， and adverse reactions during treatment were recorded. ResultCompared with the control group， the experimental group showed the decrease in the days of Gn use and dosage of Gn （P<0.05）， endometrium thickening （P<0.05）， and increase in oocytes obtained， levels of E2 and LH on the day of HCG injection， and ovarian reserve function. Moreover， in follicular fluid 36 h after HCG injection， the reduction in level of FSH （P<0.05）， rise of levels of LH and E2 （P<0.05）， and insignificant changes in levels of T and P in the experimental group were observed as compared with those in the control group. In addition， larger number of fertilization， more available embryos， and higher rate of high-quality embryos were observed in the experimental group than in the control group （P<0.05）. The experimental group demonstrated improvement in quality of oocytes， decrease in cycle cancellation rate ， and increase in clinical pregnancy rate and live birth rate compared with the control group. The TCM syndrome score in experimental group was decreased after treatment compared with that before treatment （P<0.05）. No serious adverse reactions occurred in two groups during treatment and the safety indexes before and after treatment were all within the normal ranges. ConclusionWSYX can reduce the use duration and dosage of Gn in infertile patients receiving IVF-ET， improve the quality of oocytes， increase the rate of high-quality embryos， and improve the pregnancy outcome of IVF-ET patients.

Chemical approaches towards installation of rare functional groups in bacterial surface glycans / 中国天然药物

Bacterial surface glycans perform a diverse and important set of biological roles, and have been widely used in the treatment of bacterial infectious diseases. The majority of bacterial surface glycans are decorated with diverse rare functional groups, including amido, acetamidino, carboxamido and pyruvate groups. These functional groups are thought to be important constituents for the biological activities of glycans. Chemical synthesis of glycans bearing these functional groups or their variants is essential for the investigation of structure-activity relationships by a medicinal chemistry approach. To date, a broad choice of synthetic methods is available for targeting the different rare functional groups in bacterial surface glycans. This article reviews the structures of naturally occurring rare functional groups in bacterial surface glycans, and the chemical methods used for installation of these groups.

The Formation Mechanism and Functional Implication of Chimeric RNAs / 中国生物化学与分子生物学报

Traditionally, chimeric RNA is thought to be generated by chromosome rearrangement, and its products (RNAs and proteins) were once considered as unique features of cancer. However, with the advancement of next-generation sequencing technologies and the development of bioinformatics software tools, increasing numbers of chimeric RNAs are being identified from various RNA-Seq database. Recently, numerous chimeric RNAs were discovered in human normal tissues and cell lines, with physiological functions. Besides chromosome rearrangement, chimeric RNAs are formed by different molecular mechanisms, including trans-splicing, cis-splicing of adjacent genes. Chimeric RNAs, without chromosomal changes, are regulated at the transcriptional level, and they show specific physiological functions and regulation patterns. Their dysregulation may induce cell differentiation and tumorogenisis. In addition, chimeric RNAs also play roles in normal cell growth and/or migration, cell cycle and apoptosis, induce genomic aberration by influencing chromosome rearrangement, act as potential competitive endogenous RNA, and influence stem cell differentiation. The expression of chimeric RNAs in specific tissues and cell development stages has the potential to be used as diagnostic and therapeutic biomarkers. Histological mapping studies can improve the specificity of treatment for unique cell types, and the chimeric RNA provides a new perspective to achieve this goal. The widespread existence of chimeric RNAs suggests that they may extend the diversity of genomes in human and higher animals.

The biological information and experimental verification of studying on Qingjie HuaGong decoction inhibiting inflammatory response of SAP model rats induced by cerulein based on TLR4/NF-kB/MYD88 pathway / 中国药理学通报

Aim To study the protective effect of Qingjie HuaGong decoction ( QJHGD) for severe acute pancreatitis ( SAP ) model rats induced by cerulein based on TLR4/NF-kB/MYD88 pathway.Methods The effective component groups and potential targets of QJHGD were collected by network pharmacology method , and we constructed the component-target network.The GO and KEGG of important targets were enriched and analyzed by metascape database, and we selected the targeted pathways related with SAP inflammation mechanism.The rat model of severe acute pancreatitis was established by cerulein combined with lipopolysac- charide, followed by QJHGD gavage.Pancreatic tissues were observed by hematoxylin and eosin staining.We verified the therapeutic effect of QJHGD on SAP rats and the regulatory effect on TLR4/NF-kB/MyD88 target pathway, by Enzyme linked immunosorbent and immunohistochemistry methods.Results A total of 105 active components and 148 key targets for SAP were screened; KEGG was enriched 320 different channels including toll like receptor and NF-kB classical pathways.Animal experiments showed that QJHGD harl protective changes in pancreatic pathological tissues, which was observed by HE staining; QJHGD reduced amylase, lipase, 1L-6 and TNF-a in SAP rat serum, inhibiting the positive expression of key proteins on TLR4/N F- kB/MyD88 inflammatory transduction j j pathways.Conclusion The mechanisms of QJHGD protecting pancreatic injury of SAP rat may be related to reducing the expression of key proteins on TLR4/ NF-kB/MvD88 pathway.

Molecular mechanism of rhubarb in treatment of acute pancreatitis based on network pharmacology and molecular docking / 中国药理学通报

Aim To analyze the molecular mechanism of rhubarb in the treatment of aeute pancreatitis ( AP) by network pharmacology and molecular docking.Methods TCMSP,TCMID and Swiss target predic¬tion databases were used to screen the active compo¬nents and targets of rhubarb,and genecards and OMIM databases were used to screen the targets of AP.Then the active ingredient drug target network of rhubarb and theactive ingredient disease target network of rhubarb for AP were constructed by using Cytoscape software.PPI network was constructed in string database, and go and KEGG enrichment analysis was performed in metascape database and R language.Finally,molecular docking was used to verify the possibility of binding the core active components to the core target.Results A total of 192 active components and 1 882 AP targets were obtained.The first three active components of rhubarb in the treatment of AP were beta sitosterol, aloe emodin and eupatin.The core target of rhubarb in the treatment of AP was hsp90aal.Go enrichment analysis focused on reaction to toxic substances, while KEGG enrichment analysis was significantly enriched in p53 signaling pathway closely related to AP.Molecular docking showed good binding and stable conformation.Conclusions Rhubarb can affect the expression of AP related genes and proteins through p53 signaling pathway, thereby inhibiting cell apoptosis and allevia¬ting the inflammatory injury of AP.

The effect of occupational stress on anxiety of nursing staff in a third-grade general hospital and mediating effect of job burnout / 中华劳动卫生职业病杂志

Objective: To explore the mediating effect of job burnout of nursing staff in clinical departments on occupational stress and anxiety, and to provide scientific basis for the formulation of intervention measures to relieve anxiety. Methods: From November 2020 to January 2021, a cross-sectional survey was conducted to investigate the basic situation, occupational stress, job burnout and anxiety of 653 nursing staff in a third class A general hospital in Hebei Province. Spearman rank correlation was used to analyze the relationship between occupational stress, job burnout and anxiety, stepwise regression and mediating effect model were used to verify the mediating effect of job burnout on the relationship between occupational stress and anxiety. Results: 551 valid questionnaires were collected with effective recovery of 84.38%. The incidence of high occupational stress was 68.06% (375/551) , the incidence of job burnout was 63.70% (351/551) [high, moderate and moderate were 11.07% (61/551) and 52.63% (290/551) respectively], and the incidence of anxiety was 55.72% (307/551) [mild, moderate and severe were 38.11% (210/551) , 8.53% (47/551) and 9.08% (50/551) respectively]. Occupational stress was positively correlated with job burnout and anxiety (r=0.545, 0.479) , and job burnout was positively correlated with anxiety (r=0.542, P<0.05) . The mediating effect analysis showed that occupational stress had a statistically significant effect on anxiety (c=0.509, P<0.001) , and the mediating effect of job burnout on the relationship between occupational stress and anxiety accounted for 44.99% of the total effect. Conclusion: The anxiety level of the nursing staff in this third-class A general hospital was relatively high. Job burnout has a mediating effect between occupational stress and anxiety, and anxiety of nursing staff can be alleviated by reducing occupational stress or job burnout.

Oligometastatic and oligoprogressive esophageal squamous cell carcinoma:clarifying conceptions and surgery perspectives / 中华外科杂志

The oligometastatic and oligoprogressive state has been a hot issue in cancer research. Its indolent tumor behavior, representing a novel therapeutic opportunity, has been identified as a clinical subtype in several malignancies. However, the clinical implications of the oligometastatic and oligoprogressive state in esophageal squamous cell carcinoma (ESCC) have not been thoroughly elucidated. There are still controversies regarding the existence of the oligometastatic state in ESCC, if the solitary regional lymph node metastasis should be viewed as oligoprogressive disease after esophagectomy, and the role of surgery and radiotherapy in ESCC oligometastatic disease. Despite many exciting contributions to the literature on these, further exploration is warranted. Thus, fostering the advance of research and scientific knowledge on the biological and prognostic characteristics scrupulously would facilitate personalizing treatment strategy for better outcomes.

Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase Ⅱ trial / 中华肿瘤杂志

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

The promotion of bone formation at the tendon-bone interface after ACL reconstruction with De-BMSCs transplantation and its mechanism / 中华骨科杂志

Objective:This study aimed to investigate the effect of differentiation osteogenic bone marrow mesenchymal stem cells (De-BMSCs) transplantation on the promotion of bone formation at the tendon-bone interface after anterior cruciate ligament reconstruction (ACLR), and further explored the molecular mechanism of the enhanced osteogenic effect of De-BMSCs.Methods:BMSCs from femur and tibia of New Zealand White rabbit were subjected to osteogenic induction and then cultured in no osteogenic factor medium; the obtained cell population was termed De-BMSCs. De-BMSCs were induced into osteo-, chondro-and adipo-differentiation in vitro to examine the characteristics of primitive stem cells. ACLR model with a semitendinosus tendon were performed in 48 adult rabbits, three groups were established: control group with alginate gel injectionat the tendon-bone interface, BMSCs group with the injection of alginate gel containing BMSCs, De-BMSCs group with the injection of alginate gel containing De-BMSCs. At 4 and 12 weeks after surgery, rabbits in each group were sacrificed to evaluate tendon-bone healing by histologic staining, micro-CT examination, and biomechanical test. During osteogenic differentiation of De-BMSCs, si-RNA of nuclear factor of activated T cells 2 (NFATc2) si-RNA of nuclear factor of activated T cells 1 (NFATc1) were used to verify the molecular mechanism of enhanced osteogenic effect of De-BMSCs.Results:De-BMSCs exhibited some properties similar to BMSCs including multiple differentiation potential and cell surface marker. At 4 weeks after surgery, the BV/TV value of the De-BMSCs group 0.36±0.01 was significantly higher than that of the control group 0.24±0.03 and BMSCs group 0.30±0.02 (all P<0.05), and the maximum load 40.34±1.19 N and stiffness 20.67±2.14 N/mm were significantly higher than those in the control group 14.88±2.74N, 8.67±2.19 N/mm and the BMSCs group 26.31±1.76 N, 13.81±2.14 N/mm (all P<0.05). At 12 weeks after surgery, the BV/TV value of the De-BMSCs transplantation group 0.47±0.02 was significantly higher than that of the control group 0.30±0.02 and the BMSCs group 0.35±0.03 (all P<0.05), and the maximum load 64.46±6.69 N and stiffness 25.18±3.11 N/mm were significantly higher than those in the control group 41.01±6.12 N, 11.59±2.54 N/mm and the BMSCs group 48.21±4.12 N, 15.89±2.94 N/mm (all P<0.05). During the osteogenic differentiation of De-BMSCs, the expressions of Nanog and NFATc1 were synergistically increased which promoted interaction of NFATc1 and Osterix ( P< 0.05), resulting in the increased expression of osteoblast marker genessuch as COL1A, OCN, OPN (all P< 0.05). Conclusion:De-BMSCs transplantation could promote bone formation at the tendon-bone interface after ACLR,Nanog/NFATc1/Osterix signaling pathway mediated the enhancement of the osteogenic differentiation effect of De-BMSCs.