Reappraisals of biological behaviors of PDGFRA mutant gastrointestinal stromal tumor / 中华病理学杂志

Objective: To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification. Methods: A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically. Results: There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant (P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference (P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant (P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant (P<0.001). Conclusions: GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.

Construction and reliability and validity test of knowledge, attitude and practice questionnaire on Helicobacter pylori infection in physical examination population / 中国实用护理杂志

Objective:To develop a questionnaire on knowledge, attitude and practice of Helicobacter pylori (Hp) infection among physical examination population, and to verify its reliability and validity.Methods:This study was a cross-sectional survey. Based on the theory of knowledge, attitude and practice, the first draft of the questionnaire on knowledge, attitude and practice of Hp infection in physical examination population was designed by means of retrospective literature research, qualitative interview, discussion in the research group. The structure and items of the questionnaire were consulted and revised by the expert consultation method (Delphi method). Through pre investigation of 186 physical examination personnel from May to June in 2021, the final version of the "knowledge, attitude and practice questionnaire on Helicobacter pylori infection among physical examination population" was formed after adjustment and verification of the reliability and validity of the questionnaire.Results:The questionnaire of knowledge, attitude and practice of Hp infection in physical examination population included 3 dimensions and 28 items, and the cumulative variance contribution rate was 56.271%. The content validity index of each item level of the questionnaire was 0.75-1.00, and the content validity index of the total questionnaire was 0.94. The Cronbach alpha of knowledge, attitude and practice dimensions in this questionnaire were 0.862, 0.901 and 0.798 respectively. The overall Cronbach alpha of the questionnaire was 0.890, and the half reliability was 0.698. The test-retest reliability of the questionnaire was 0.919, and the test-retest reliability of each dimension was 0.924, 0.917 and 0.845.Conclusions:The questionnaire has good reliability and validity, and can be used to measure the level of knowledge, attitude and practice of Hp infection in physical examination population.

Developmental comparison between cerebral organoids in vitro and body's cortices in vivo / 解剖学报

Objective To understand the characteristics and developmental differences between cerebral organoids in vitro and normal cerebral cortices in vivo. Methods 1. Grouping: cerebral cortices in vivo group and cultured cerebral organoids in vitro group. 2. Sample collection: cortical tissues were collected from Kunming mouse embryos at embryonic day 7.5(E7.5), E9.5, E11.5, E14.5, and postnatal day 3 (P3) or P7. Three specimens were taken from each group. Meanwhile, cerebral organoids were cultured with mouse induced pluripotent stem cells (iPSCs), and samples at different culture time point were collected, and more than 3 samples were collected at each time point. 3. Detection method: the distribution of different types of cells in each group of specimens was analyzed by immunofluorescent staining. Results While relative similarities between in vivo cerebral cortical development and the cerebral organoids in vitro were observed, including the histogenesis, and the morphological differentiation of nerve cells and glial cells, the lamellar architecture of cerebral cortex in mouse brain was not observed in cerebral organoids. Conclusion The development of cerebral organoids in vitro has some similarity with body's cortical development. Therefore, cerebral organoids can be used to a substitution of cortex and diseases' models, but improvement of the existing technologies is necessary.

Mechanism of Bawei Chenxiang powder in treatment of ischemie heart disease through mitophagy based on network pharmacology / 中国药理学通报

Aim To explore the potential mechanism of Bawei Chenxiang powder against ischemie heart disease (IHD) through mitophagy based on network pharmacology, molecular docking and verification in vitro. Methods The targets of serum constituents of Bawei Chenxiang powder were mined by Swiss target predic-tion, and then the targets related to IHD and mitophagy were selected from Genecards, NCBI and OMIM data-bases to obtain the intersection targets of the three as the potential targets of Bawei Chenxiang powder for the treatment of IHD through mitophagy. Then the "ingre-dients-disease-potential target " network and " protein-protein interaction" (PPI) network were constructed to perform network analysis in order to screen the key ac-tive ingredients and core targets, using Autodock vina software for molecular docking operation. The targets CO function enrichment analysis and KEGG pathway enrichment analysis were analyzed by DAVID databas-es. The effeets of Bawei Chenxiang powder containing serum on celi viability, levels expressions mitophagy and key signaling pathway related protein in H9C2 cells were investigated by hypoxia-induced injury of H9c2 myocardial cells model in vitro. Results The 9 key active compounds and 8 core targets of Bawei Chenxiang powder were screened; molecular docking showed a good binding ability of key active ingredients and core targets. KEGG pathway enrichment analysis showed that the effect of Bawei Chenxiang powder on IHD through mitophagy was related to EGFR, PI3K-Akt, MAPK, FoxO signaling pathway, etc. Celi ex-periments showed that Bawei Chenxiang powder containing serum treatment could significantly improve the survival rate by hypoxia-induced injury in H9c2, the expression of LC3II and p62 were significantly down-regulated, and the expressions of p-PI3K/PI3K and p-AKT/AKT were significantly up-regulated. Conclu-sions Bawei Chenxiang powder plays an anti-IHD role by regulating mitophagy, which may be involved in AKT1, STAT3, MAPK3 and EGFR and other targets, through quercetin, Kaempferol, Naringenin and De-hydrodiisoeugenol as well as other components. Its mechanism may be related to improving PI3K-AKT pathway.

Effect of Gualou Xiebai Decoction on type II cardiorenal syndrome based on endothelial/epithelial-to-mesenchymal transition and its mechanism / 中国药理学通报

Aim To investigate the protective effects of different doses Gualou Xiebai Decoction (GXD) on type II cardiorenal syndrome (type II CRS) and explore its preliminary mechanisms. Methods The type II cardiorenal syndrome rat model was replicated by li-gating the left anterior descending coronary artery. After 10 weeks of intragastric administration, the cardiac function of the rats in each group was evaluated by echocardiography; serum were collected for biochemical testing; heart and kidney tissue samples were stained with HE and Masson to observe pathological changes. The hydroxyproline content in the heart and kidney was detected. The expression levels of endothelial/epitheli-al-to-mesenchymal transition (EndMT/EMT) related proteins in heart and kidney tissues were detecterd by immunofluorescence double staining

Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study / 中国当代儿科杂志

OBJECTIVES@#To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia.@*METHODS@#A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively.@*RESULTS@#Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia.@*CONCLUSIONS@#The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.

Clinicopathological features and prognostic factors of gastric intermediate-risk gastrointestinal stromal tumor after surgical resection: a retrospective study / 中华病理学杂志

Objective: To investigate the clinicopathological features, treatment and prognosis of gastric intermediate-risk gastrointestinal stromal tumor (GIST), so as to provide a reference for clinical management and further research. Methods: A retrospective observational study of patients with gastric intermediate-risk GIST, who underwent surgical resection between January 1996 and December 2019 at Zhongshan Hospital of Fudan University, was carried out. Results: Totally, 360 patients with a median age of 59 years were included. There were 190 males and 170 females with median tumor diameter of 5.9 cm. Routine genetic testing was performed in 247 cases (68.6%, 247/360), and 198 cases (80.2%) showed KIT mutation, 26 cases (10.5%) showed PDGFRA mutation, and 23 cases were wild-type GIST. According to "Zhongshan Method"(including 12 parameters), there were 121 malignant and 239 non-malignant cases. Complete follow-up data were available in 241 patients; 55 patients (22.8%) received imatinib therapy, 10 patients (4.1%) experienced tumor progression, and one patient (PDGFRA mutation, 0.4%) died. Disease-free survival (DFS) and overall survival rate at 5 years was 96.0% and 99.6%, respectively. Among the intermediate-risk GIST, there was no difference in DFS between the overall population, KIT mutation, PDGFRA mutation, wild-type, non-malignant and malignant subgroups (all P>0.05). However, the non-malignancy/malignancy analysis showed that there were significant differences in DFS among the overall population (P<0.01), imatinib treatment group (P=0.044) and no imatinib treatment group (P<0.01). Adjuvant imatinib resulted in potential survival benefit for KIT mutated malignant and intermediate-risk GIST in DFS (P=0.241). Conclusions: Gastric intermediate-risk GIST shows a heterogeneous biologic behavior spectrum from benign to highly malignant. It can be further classified into benign and malignant, mainly nonmalignant and low-grade malignant. The overall disease progression rate after surgical resection is low, and real-world data show that there is no significant benefit from imatinib treatment after surgery. However, adjuvant imatinib potentially improves DFS of intermediate-risk patients with tumors harboring KIT mutation in the malignant group. Therefore, a comprehensive analysis of gene mutations in benign/malignant GIST will facilitate improvements in therapeutic decision-making.

New research advances in hypertrophic scar formation, prevention and treatment / 中华预防医学杂志

Scarring, naturally induced by fibroblasts(Fb) during wound healing, is an essential process in response to repair damaged tissue. Excessive Fb proliferation which produces the excessive collagen deposition, including increased extracellular matrix synthesis or insufficient decomposition, typically contributes to hypertrophic scar(HS) formation. Although exact mechanisms of HS are not yet fully understood, it is generally believed that dysfunction of Fb and regulation of signal pathways play an important role in HS formation. Biologically, Fb function is affected by various factors such as cytokines, extracellular matrix and itself. In addition, modifications of miRNA, ceRNA, lncRNA, peptides and histones participate in HS formation by affecting the biological function of Fb. Despite the clinical importance, very few therapeutic modalities are available to prevent HS. To achieve this, a deeper characterization of Fb is required to identify mechanisms of HS. To the aspect of HS prevention and treatment, we review recent findings, concentrating on Fb function and collagen secretion. The objective of this article is to frame the current understanding, gain the deeper insights into Fb function, and provide the more comprehensive cognition and perspective for prevention and treatment of HS.

Current Status and Challenges of Research on Biomarkers of Barrett’s Esophagus in Risk Stratification / 胃肠病学

Barrett’s esophagus (BE) is the recognized precancerous lesion and risk factor for esophageal adenocarcinoma (EAC), and has a high miss diagnosis rate and low survival rate when malignantly transformed into EAC, moreover, there are only limited monitoring method and treatment. Therefore, the screening of biomarkers is highly expected, especially the risk stratification biomarkers related to the progression of malignant transformation of BE. Such biomarkers can help to determine early, quickly and accurately the disease process, and guide the stratified management and precise treatment of BE, reduce the malignancy rate and mortality. This article focused on the dynamic evolutionary process of intra‑tumor heterogeneity, and reviewed the current status and challenges of research on BE biomarkers in risk stratification from the genetics, epigenetics and serology perspectives.

Effects of PINK1 mediated mitophagy on senescence and function of rat bone marrow endothelial progenitor cells / 中国药理学通报

Aim To investigate the effects of PTEN-induced putative kinase1(PINK1)mediated mitophagy on senescence and function of rat bone marrow endothelial progenitor cells(EPCs)by using small interfering RNA(siRNA)technology to knock down the PINK1 gene in rat bone marrow EPCs.Methods EPCs from bone marrow in rats were isolated, cultured and identified.After counting, EPCs were randomlydivided into control group, negative control group(NC siRNA), and Pink1 transfection group(PINK1 siRNA).The expression of PINK1 mRNA and protein in cells in various groups were detected by qRT-PCR and Western blot.At the same time, different time points were chosen to simulate the aging process based on the best knock down time.The senescence of cells was detected by SA-β-galactosidase staining and p16 protein expression.The function of cell proliferation, migration and tubule formation was detected by CCK-8, Transwell chamber and in vitro angiogenesis kit.ROS level was detected by flow cytometry.The expressions of PINK1, Parkin, LC3, and p62 were detected by Western blot.Mitochondria and autophagosomes were observed by transmission electron microscope.Results 48 h after PINK1 siRNA transfected, PINK1 was effectively knocked down.Compared with control group, the positive rate of blue staining and the expression of p16 protein in PINK1 siRNA group increased significantly 48 h and 96 h after transfection.The function of cell proliferation, migration and tubule formation decreased significantly.The level of ROS increased significantly, while the expression of PINK1, Parkin and LC3 protein decreased significantly, and p62 protein expression increased significantly.Under the transmission electron microscope, the mitochondria swelled and denatured, and the number of autophagosomes decreased in the PINK1 siRNA group.Conclusions The down-regulation of PINK1 gene can aggravate the senescence of EPCs, and PINK1 mediated mitophagy may participate in the regulation of senescence and function of EPCs.

Research progress of gut-skin axis in three inflammatory skin diseases / 中国药理学通报

Cut and skin have many similarities that all colonized with a large number of mierobiota.Among them,gut mierobiota has an important impact on health.Gut microbiota disturbance may trigger an inflammatory response .which in turn leads to tis¬sue damage or autoimmune reactions.A large number of studies have shown that gut microbiota is closely related to skin health and the theory of gut-skin axis has also been proposed.This arti¬ cle explores the effect of gut microbiota on three common inflam¬matory skin diseases, including psoriasis, atopic dermatitis and acne vulgaris.The important role of gut microbiota in the treat¬ment of inflammatory skin diseases is also reviewed.

Exploiting DNA replication stress for sequential therapy with PARP and WEE1 inhibitors / 부인종양

We demonstrate that concurrent administration of poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors is effective in inhibiting tumor growth but poorly tolerated. Concurrent treatment with PARP and WEE1 inhibitors induces replication stress, DNA damage, and abrogates the G2 DNA damage checkpoint in both normal and malignant cells. Following cessation of monotherapy with PARP or WEE1 inhibitors, effects of these inhibitors persist suggesting that sequential administration of PARP and WEE1 inhibitors could maintain efficacy while ameliorating toxicity. Strikingly, while sequential administration mirrored concurrent therapy in cancer cells that have high basal replication stress, low basal replication stress in normal cells protected them from DNA damage and toxicity, thus improving tolerability while preserving efficacy in ovarian cancer xenograft and patient-derived xenograft models.

Medication Regularity for Chronic Renal Failure and Underlying Mechanism Based on Data Mining， Network Pharmacology， and Molecular Docking / 中国实验方剂学杂志

ObjectiveTo clarify the medication regularity of WU Zhao-dong，a famous chief physician in traditional Chinese medicine （TCM） of Jiangxi province， and investigate the potential mechanism of potential new prescriptions against chronic renal failure （CRF）. MethodThe outpatient prescriptions of WU Zhao-dong from July 2019 to July 2021 were collected. Data mining was carried out by using the Traditional Chinese Medicine Inheritance Auxiliary Platform （V 2.5） to analyze the medication frequency and drug association and obtain potential new prescriptions. The interaction between drug targets in new prescriptions was analyzed by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP），STRING，and Kyoto Encyclopedia of Genes and Genomes（KEGG）， followed by verification by molecular docking and experiments. ResultA total of 200 prescriptions were screened out， with 217 Chinese medicinal drugs involved， and eight new potential prescriptions were derived. To be specific， Prescription 1： Armeniacae Semen Amarum-Astragali Radix-Platycodonis Radix-Angelicae Sinensis Radix-Smilacis Glabrae Rhizoma-fried Atractylodis Macrocephalae Rhizoma， Prescription 2： Saposhnikoviae Radix-Schizonepetae Herba-Kochiae Fructus-Asteris Radix et Rhizoma-Menthae Haplocalycis Herba，Prescription 3：Armeniacae Semen Amarum-Asteris Radix et Rhizoma-Platycodonis Radix-Eriobotryae Folium-prepared Ephedrae Herba， Prescription 4：Perillae Caulis-Codonopsis Radix-Coptidis Rhizoma-Pseudostellariae Radix， Prescription 5：Ecliptae Herba-Astragali Radix Praeparata Cum Melle-Dryopteridis Crassirhizomatis Rhizoma-Rosae Laevigatae Fructus-Coicis Semen-Ligustri Lucidi Fructus， Prescription 6： Lycopi Herba-Lonice Raejaponicae Caulis-Trachelospermi Caulis et Folium-Alismatis Rhizoma， Prescription 7：Scutellariae Radix-Hirudo-Paeoniae Radix Rubra-Eriobotryae Folium-Glehniae Radix， Prescription 8：Glycyrrhizae Radix et Rhizoma-Scrophulariae Radix-Chrysanthemi Indici Flos-Smilacis Glabrae Rhizoma- Serissae Herba. In Prescription 1，18 main chemical components were screened out. Eighty targets of active components of Prescription 1 were predicted， and 37 potential targets for the treatment of CRF were obtained， including interleukin （IL）-6， vascular endothelial growth factor （VEGF）， cysteinyl aspartate-specific protease-3 （Caspase-3）， nitric oxide synthase 3 （NOS3）， and hypoxia-inducible factor-1 （HIF-1）. The KEGG pathways involved in the targets of Chinese medicinal drugs and disease mainly included the signaling pathways of lipid and atherosclerosis，NF-κB， Toll-like receptors， and HIF-1. Prescription 1 significantly decreased serum creatinine and urea nitrogen， and increased the content of NO and NOS3 in renal tissues of CRF rats. ConclusionPrescription 1 shows the multi-component and multi-target characteristics of action，and its mechanism may be related to its inhibition of renal fibrosis，anti-inflammation，improvement of intestinal microecology，and improvement of renal hypoxia and ischemia.

Progress in understanding hepatic fibrosis and renal fibrosis based on the gut-liver-kidney axis / 药学学报

Fibrosis is a pathological process of abnormal hyperplasia and excessive deposition of extracellular matrix during the process of repair after tissue and organ damage. Injury/inflammation caused by variously chronic diseases is a major trigger for fibrogenesis. Fibrosis of the liver and kidney is a common organ fibrosis. Recently, the intestinal microbiota has been shown to be extensively involved in the development of liver and kidney diseases, which may follow from changes in the intestinal microbial composition and intestinal integrity. This promotes the development of liver and/or kidney fibrosis through endocrine, cell signaling and other pathways. This paper reviews the research progress in understanding liver fibrosis and kidney fibrosis based on the gut-liver-kidney axis, which may be helpful for providing new strategies and theoretical basis for the diagnosis and treatment of hepatic and renal fibrosis.

The Role of SPOP During Development / 中国生物化学与分子生物学报

Aberrant expression or mutation of many genes that are essential for embryonic development, are closely associated with human diseases, one of which is SPOP (speckle type BTB/POZ protein). SPOP is an E3 ubiquitin ligase adaptor protein and mainly composed of MATH, BTB and BACK domains, which plays distinct roles to fulfill the proper function of SPOP. SPOP usually targets its substrates for degradation via the ubiquitin-proteasome pathway. More than thirty substrates of SPOP have been identified by far, most of which are associated with tumorigenesis of prostate, endometrial and kidney cancers. SPOP also plays an important role during development. Genomic loss or mutation of SPOP locus leads to postnatal lethality in mice, while de novo variants in SPOP cause neurodevelopmental disorders in children. Similarly, SPOP regulates a variety of developmental processes via targeting its substrates for degradation, including Gli2/3, PDX1, NANOG and SENP7 which are involved in neural, skeletal and pancreatic development as well as senescence. In addition, recent studies have revealed that SPOP co-localizes with its substrates into membraneless organelles such as nuclear speckles, and promotes ubiquitination and degradation of its substrates. Oligomerization of SPOP and liquid-liquid phase separation (LLPS) triggered by multivalent interactions between SPOP and substrates play a pivotal role in this process. BTB or BACK mutants, which are defective in SPOP oligomerization, are also defective in driving LLPS of SPOP and recruiting SPOP into membraneless organelles. In this review, we summarized and discussed the recent progress on the essential role of SPOP during development.

Mechanism of total C-21 steroidal glucosides from root of Cynanchum auriculatum in activation of human hepatic stellate cells via TGF-β / 中国药理学通报

Aim To investigate the inhibitory effect of total C-21 steroidal glucosides (TCSG) from the root of Cynanchum auriculatum on activation of human hepatic stellate cells and the underlying mechanism. Methods The fibrosis model in vitro was established by treating LX-2 cells with TGF-β

Clinicopathological features and prognosis of gastrointestinal stromal tumors with KIT/PDGFRA gene "homozygous mutation": a multicenter retrospective cohort study / 中华胃肠外科杂志

Objective: To investigate the clinicopathological features of gastrointestinal stromal tumor (GIST) with KIT/PDGFRA "homozygous mutation", the efficacy of targeted therapy and the prognosis. Methods: A retrospective cohort study and propensity score matching were used. "Homozygous mutation" was defined as the detection of KIT/PDGFRA gene status of GIST by Sanger sequencing, which showed that there was only mutant gene sequence in the sequencing map, lack of wild-type sequence or the peak height of mutant gene sequence was much higher than that of wild-type gene sequence (> 3 times). "Heterozygous mutation" was defined as the mutant gene sequences coexisted with wild type gene sequences, and the peak height was similar (3 times or less). The clinicopathological data and follow-up information of 92 GIST patients with KIT/PDGFRA "homozygous mutation" were collected from 4 hospitals in Shanghai from January 2008 to May 2021 (Renji Hospital, Shanghai Jiaotong University School of Medicine: 70 cases; Zhongshan Hospital, Fudan University: 14 cases; Changhai Hospital, Naval Military Medical University: 6 cases and Ruijin Hospital, Shanghai Jiaotong University School of Medicine: 2 cases). Patients with perioperative death, other malignancies, and incomplete clinicopathological information were excluded. The clinicopathological features of the patients and the efficacy of targeted drug therapy were observed and analyzed. The efficacy was evaluated using Choi criteria, which were divided into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). In addition, a total of 230 patients with high-risk GIST with "heterozygous mutation" in exon 11 of KIT gene and 117 patients with recurrent or metastatic GIST with "heterozygous mutation" in exon 11 of KIT gene were included. The propensity score matching method was used to match GIST patients with "heterozygous" and "homozygous" mutations in exon 11 of KIT gene (1∶1) for survival analysis. The disease-free survival (DFS) between two groups of high-risk GIST patients who underwent complete surgical resection were compared. And progression-free survival (PFS) in patients with recurrent or metastatic GIST were compared. Results: Of the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 58 were males and 34 were females, with a median onset age of 62 (31-91) years. Primary GIST 83 cases. Primary high-risk GIST (53 cases), metastatic GIST (21 cases) and recurrent GIST (9 cases) accounted for 90.2% (83/92). There were 90 cases of KIT gene"homozygous mutation" (exon 11 for 88 cases, exon 13 for 1 case, exon 17 for 1 case), and 2 cases of PDGFRA gene "homozygous mutation" (exon 12 for 1 case, exon 18 for 1 case). The median follow-up time was 49 (8-181) months. Among the 61 cases of primary localized GIST undergoing complete surgical resection, 2 cases were intermediate-risk GIST, 5 cases were low-risk GIST, and 1 case was very low-risk GIST, of whom 1 case of intermediate-risk GIST received 1-year adjuvant imatinib mesylate (IM) therapy after operation, and no tumor recurrence developed during the follow-up period. The remaining 53 cases were high-risk GIST, and follow-up data were obtained from 50 cases, of whom 22 developed tumor recurrence during follow-up. Of 9 patients directly receiving neoadjuvant targeted therapy (IM or avapritinib), 5 had complete imaging follow-up data, and the evaluation of efficacy achieved PR. Of all the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 50 (54.4%) had tumor metastasis or tumor recurrence or progression during follow-up, and 12 (13.0%) died of the tumor. Survival analysis combined with propensity score showed that in 100 cases of high-risk GISTs with complete resection, GISTs with "homozygous mutation" in exon 11 of KIT gene had shorter disease-free survival (DFS) than GISTs with "heterozygous mutation" in exon 11 of KIT gene (median DFS: 72 months vs. 148 months, P=0.015). In 60 cases of recurrent or metastatic GISTs with KIT gene exon 11 mutation, IM was used as the first-line treatment, and the progression-free survival (PFS) of GISTs with "homozygous mutation" was shorter compared to GISTs with "heterozygous mutation" (median PFS: 38 months vs. 69 months, P=0.044). The differences were statistically significant. Conclusions: "Homozygous mutation" in KIT/PDGFRA gene is associated with the progression of GIST. The corresponding targeted therapeutic drugs are still effective for GIST with KIT/PDGFRA gene "homozygous mutation". Compared with GIST patients with "heterozygous mutation" in KIT exon 11, GIST patients with "homozygous mutation" in KIT exon 11 are more likely to relapse after surgery and to develop resistance to IM. Therefore, it is still necessary to seek more effective treatment methods for this subset of cases.

Expert Consensus for Thermal Ablation of Pulmonary Subsolid Nodules (2021 Edition) / 中国肺癌杂志

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
.

Intramedullary nailing through suprapatellar approach with semiextended position for the treatment of tibial fractures / 中国骨伤

OBJECTIVE@#To explore clinical effects of intramedullary nailing through suprapatellar approach with semiextended position in treating tibial fractures.@*METHODS@#From January 2018 to June 2019, 23 patients with tibia fractures were treated with suprapatellar approach intramedullary nailing on knee semiextended position, including 18 males and 5 females, aged from 26 to 67 years old with an average age of (38.5±9.6) years old. Eight patients were tibial proximal fractures, 7 patients were tibial shaft fractures, 6 patients were tibial distal fractures and 2 patients were tibial segmental fractures. Operation time, intraoperative blood loss, complications and fracture healing time were recorded. Range of motivation of knee joint between 3 days and 3 months after operation were compared, Hospital for Special Surgery (HSS) score and visual analogue scale (VAS) were used to evaluate clinical effects.@*RESULTS@#All patients were followed up from 8 to 19 months with an average of (12.3±7.6) months. Operation time was (55.3±5.1) min, intraoperative blood loss was (84.0±8.7) ml. No obvious complications occurred. All patients were achieved bony union at stageⅠ, fracture healing time ranged from 3 to 8 months with an average of (4.6±1.5) months. Flexion extension range of knee motion at 3 days after operation was (110.4±15.3)°, and increased to (123.7±16.5)° at 3 months after operation (@*CONCLUSION@#Intramedullary nailing through suprapatellar approach with semiextended position in treating tibia fractureshas advantages of simple operation, less trauma for soft tissue, less pain, rapid recovery of function and less complication. It is especially suitable for patients with tibial multi-segment fracture and multiple fractures of ipsilateral lower limb for safety and simple.

A clinical epidemiological investigation of neonatal acute respiratory distress syndrome in southwest Hubei, China / 中国当代儿科杂志

OBJECTIVE@#To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China.@*METHODS@#According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017.@*RESULTS@#A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66).@*CONCLUSIONS@#Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.