1.Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance
Xianlong WANG ; Chuan ZHAO ; Jincheng LIN ; Hongxing LIU ; Qiuhong ZENG ; Huadong CHEN ; Ye WANG ; Dapeng XU ; Wen CHEN ; Moping XU ; En ZHANG ; Da LIN ; Zhixiong LIN
Chinese Medical Journal 2024;137(7):859-870
Background::Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods::Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results::Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). Conclusions::ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.
2.Effects of comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome.
Shun Tang LI ; Yuan LIN ; Bin Xian OU ; Da En LIU ; De Hui LI ; Qing Wen NONG ; Ya Jun WU ; Shu Mei QIU ; Zhen Xing HUANG
Chinese Journal of Burns 2022;38(6):512-519
Objective: To investigate the characteristics and comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome. Methods: A retrospective observational study was conducted. From May 2012 to December 2021, the data of 19 patients with iatrogenic Cushing's syndrome discharged from the Department of Burns and Plastic Surgery of the First Affiliated Hospital of Guangxi Medical University were collected, including 8 males and 11 females, aged 28-71 (56±11) years, with 12 cases of infected acute wounds and 7 cases of infected chronic wounds. The lesions were located in the limbs, perianal, and sacrococcygeal regions, with original infection ranging from 9 cm×5 cm to 85 cm×45 cm. After admission, the patients were performed with multidisciplinary assisted diagnosis and treatment, and the wounds were treated with debridement and vacuum sealing drainage, according to the size, severity of infection, suture tension, and bone and tendon tissue exposure of wounds, direct suture or autologous skin and/or artificial dermis and/or autologous tissue flap transplantation was selected for wound repair. The levels of cortisol and adrenocorticotropic hormone (ACTH) of patients at 8:00, 16:00, and 24:00 within 24 h after admission were counted. After admission, the number of operations, wound repair methods, and wound and skin/flap donor site healing of patients were recorded. During follow-up, the wounds were observed for recurrent infection. Results: The cortisol levels of 16 patients at 8:00, 16:00, and 24:00 within 24 h after admission were (130±54), (80±16), and (109±39) nmol/L, respectively, and ACTH levels were (7.2±2.8), (4.1±1.8), and (6.0±3.0) pg/mL, respectively; and the other 3 patients had no such statistical results. After admission, the number of surgical operation for patients was 3.4±0.9. The following methods were used for wound repair, including direct suturing in 4 cases and autologous skin and/or artificial dermis grafting in 9 cases, of which 2 cases underwent stage Ⅱ autologous skin grafting after artificial dermis grafting in stage Ⅰ, and 6 cases had pedicled retrograde island flap+autologous skin grafting. The wound healing was observed, showing that all directly sutured wounds healed well; the wounds in 6 cases of autologous skin and/or artificial dermis grafting healed well, and the wounds in 3 cases also healed well after the secondary skin grafting; the flaps in 4 cases survived well with the wounds in 2 cases with distal perforators flap arteries circumfluence obstacle of posterior leg healed after stage Ⅱ debridement and autologous skin grafting. The healing status of skin/flap donor sites was followed showing that the donor sites of medium-thickness skin grafts in the thigh of 4 cases were well healed after transplanted with autologous split-thickness grafts from scalp; the donor sites of medium-thickness skin grafts in 3 cases did not undergo split-thickness skin grafting, of which 2 cases had poor healing but healed well after secondary skin grafting 2 weeks after surgery; the donor sites of split-thickness skin grafts in the head of 2 patients healed well; and all donor sites of flaps healed well after autologous skin grafting. During follow-up of more than half a year, 3 gout patients were hospitalized again for surgical treatment due to gout stone rupture, 4 patients were hospitalized again for surgical treatment due to infection, and no recurrent infection was found in the rest of patients. Conclusions: The infected wounds in patients with iatrogenic Cushing's syndrome have poor ability to regenerate and are prone to repeated infection. Local wound treatment together with multidisciplinary comprehensive treatment should be performed to control infection and close wounds in a timely manner, so as to maximize the benefits of patients.
Adrenocorticotropic Hormone
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China
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Cushing Syndrome/surgery*
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Female
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Gout
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Humans
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Hydrocortisone
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Iatrogenic Disease
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Male
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Skin, Artificial
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Wound Infection
3. EHD2 Affects the Proliferation of Esophageal Squamous Cell Carcinoma by Regulating the Cyclin Dl-CDK4-pRb Signaling Axis
Zhi-Da ZHANG ; Dan-Xia DENG ; Bing WEN ; Liu PENG ; Ke DONG ; De-Yuan PAN ; Lian-Di LIAO ; Li-Yan XU ; En-Min LI ; Hai-Xiang ZHENG ; Li-Yan XU ; De-Yuan PAN ; Li-Yan XU
Chinese Journal of Biochemistry and Molecular Biology 2022;38(9):1174-1192
Actin-binding proteins (ABPs) are important components of the F-actin cytoskeleton and affect the dynamics of F-actin by promoting the polymerization and depolymerization of actin. Numerous studies have shown that F-actin and actin-binding proteins are involved in all stages of carcinogenesis. Our analysis of esophageal carcinoma proteomic data showed that the actin-binding protein EHD2 (E p s l 5 homology domain-containing protein 2) is expressed at low levels in esophageal squamous cell carcinoma tissues and patients with lower EHD2 expression had poorer prognosis. Previous studies have revealed that EHD2 is involved in the regulation of glucose metabolism, autophagy and tumor cell migration. However, the role and mechanism of EHD2 in esophageal squamous cell carcinoma progression remain unclear. This study aimed to explore the effect of EHD2 on the proliferation of esophageal squamous cell carcinoma. Immunofluorescence and cell fractionation analysis showed that EHD2 was not only localized in the cell membrane and cytoplasm, but also in the nucleus. Colony formation, EdU labeling and flow cytometry were used to determine the effect of EHD2 on the proliferation of esophageal squamous cell carcinoma. The results showed that overexpression of EHD2 and EHD2-3×NLS (nuclear localization signal) inhibited proliferation, cell cycle G
4.Research Progress on Estimation of Postmortem Submersion Interval.
Hui Ya YUAN ; Rui ZHAO ; Li Na GAO ; En Yu XU ; Lin Lin WANG ; Da Wei GUAN ; Jun Ting LIU
Journal of Forensic Medicine 2020;36(6):801-806
Postmortem interval (PMI) estimation is one of the most important and difficult academic tasks in forensic sciences. Due to the influence of the corpse itself and the water environment, corpses in water have unique corruption phenomenon and laws. Based on the experience of traditional PMI studies of corpses on land, forensic practitioners across the world have proposed a variety of practical methods for estimating postmortem submersion interval (PMSI). This paper summarizes the literatures related to PMSI in recent years, and introduces methods to infer PMSI according to the phenomenon of corpses, the development of insects, the succession pattern of aquatic organisms, and the changes of other physical and chemical indexes of corpses, in order to provide some reference for the study of PMSI of corpses in water.
Animals
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Autopsy
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Cadaver
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Forensic Medicine
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Immersion
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Postmortem Changes
5.Preparation and detection of pipettes for microinjection
xin Da CHENG ; ran Li XU ; qing Qing YU ; cui Shou GAO ; jing Xiao WANG ; Yi LIU ; qi En LIU ; hai Si ZHAO
Journal of Xi'an Jiaotong University(Medical Sciences) 2017;38(6):917-920
Objective To introduce an optimized practical method of making and detecting pipettes for microinjection.Methods Transfer pipette was made from hard glass capillary. We softened the hard glass capillary by rotating it in a spirit-lamp flame,then moved out from the flame and quickly pulled it into two transfer pipettes.After broken by a grinding wheel,the tip of the pipette was fire-polished by quickly touching the flame to make a fine opening.A hard glass capillary (1.0 mm,ouside diametre)was pulled into two holding pipettes by pipette Puller.The pipette shoulder was broken at desired position with a grinding wheel,then the fine pipette tip opening was heated by a microforge and shrinked into a diameter -15 μm.Injection pipette could be made directly from a capillary with filament by Puller.The solution loaded injection pipette and holding pipette were assembled into the micromanipulator and could be checked before use.We transfered both pipettes into the zygotes media drop,touched the holding pipette with the tip of the injection pipette to make a "suitable"opening.Then we switched injection pipette to the mineral oil and applied injection pressure through the injector to check whether the solution could come out of the tip smoothly and at a proper speed.It could be further verified by pronucleus microinjection of zygotes.Results The results showed that the method introduced in this paper could produce suitable pipettes for zygote microinjection.In particular,the method of detecting the opening of the injection pipette was helpful for achieving high efficiency of zygote microinjection.Conclusion The method introduced here to make and detect pipettes for microinjection is very helpful for establishing a standard microinjection manipulation procedure and improving the efficiency of zygote microinjection.
6.Andrographolide as an anti-H1N1 drug and the mechanism related to retinoic acid-inducible gene-I-like receptors signaling pathway.
Bin YU ; Cong-qi DAI ; Zhen-you JIANG ; En-qing LI ; Chen CHEN ; Xian-lin WU ; Jia CHEN ; Qian LIU ; Chang-lin ZHAO ; Jin-xiong HE ; Da-hong JU ; Xiao-yin CHEN
Chinese journal of integrative medicine 2014;20(7):540-545
OBJECTIVETo observe the anti-virus effects of andrographolide (AD) on the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) signaling pathway when immunological cells were infected with H1N1.
METHODSLeukomonocyte was obtained from umbilical cord blood by Ficoll density gradient centrifugation, and immunological cells were harvested after cytokines stimulation. Virus infected cell model was established by H1N1 co-cultured with normal human bronchial epithelial cell line (16HBE). The optimal concentration of AD was defined by methyl-thiazolyl-tetrazolium (MTT) assay. After the virus infected cell model was established, AD was added into the medium as a treatment intervention. After 24-h co-culture, cell supernatant was collected for interferon gamma (IFN-γ) and interleukin-4 (IL-4) enzyme-linked immunosorbent assay (ELISA) detection while immunological cells for real-time polymerase chain reaction (RT-PCR).
RESULTSThe optimal concentration of AD for anti-virus effect was 250 μg/mL. IL-4 and IFN-γ in the supernatant and mRNA levels in RLRs pathway increased when cells was infected by virus, RIG-I, IFN-β promoter stimulator-1 (IPS-1), interferon regulatory factor (IRF)-7, IRF-3 and nuclear transcription factor κB (NF-κB) mRNA levels increased significantly (P<0.05). When AD was added into co-culture medium, the levels of IL-4 and IFN-γ were lower than those in the non-interference groups and the mRNA expression levels decreased, RIG-I, IPS-1, IRF-7, IRF-3 and NF-κB decreased significantly in each group with significant statistic differences (P<0.05).
CONCLUSIONSThe RLRs mediated viral recognition provided a potential molecular target for acute viral infections and andrographolide could ameliorate H1N1 virus-induced cell mortality. And the antiviral effects might be related to its inhibition of viral-induced activation of the RLRs signaling pathway.
Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Antiviral Agents ; pharmacology ; Cells, Cultured ; Coculture Techniques ; DEAD Box Protein 58 ; DEAD-box RNA Helicases ; genetics ; metabolism ; Dendritic Cells ; drug effects ; immunology ; virology ; Diterpenes ; pharmacology ; Fetal Blood ; cytology ; Humans ; Influenza A Virus, H1N1 Subtype ; drug effects ; immunology ; Influenza, Human ; drug therapy ; immunology ; virology ; Interferon-beta ; genetics ; metabolism ; Interferon-gamma ; metabolism ; Interleukin-4 ; metabolism ; Leukocytes, Mononuclear ; drug effects ; immunology ; virology ; Macrophages ; drug effects ; virology ; NF-kappa B ; genetics ; metabolism ; Promoter Regions, Genetic ; drug effects ; immunology ; RNA, Messenger ; metabolism ; Signal Transduction ; drug effects ; genetics ; immunology
7.Emergence application of colonoscopic placement of self-expandable metal stent without fluoroscopic monitoring.
Zheng LOU ; En-da YU ; Wei ZHANG ; Lian-jie LIU ; Li-qiang HAO ; Han-tao WANG ; Rong-gui MENG ; Chuan-gang FU
Chinese Journal of Gastrointestinal Surgery 2013;16(4):363-366
OBJECTIVETo evaluate the efficacy and safety of colonoscopy-guided placement of self-expandable metallic stent without fluoroscopic monitoring in the emergence management for acute malignant colorectal obstruction.
METHODSClinical data of 42 patients (24 males and 18 females with a mean age of 64.3 years) undergoing colonoscopy-guided placement of self-expandable metallic stents without fluoroscopic monitoring for acute malignant colorectal obstruction between January 2010 and June 2012 were reviewed retrospectively.
RESULTSThe obstruction was located in the rectum (n=19), sigmoid (n=9), descending colon (n=8), splenic flexure (n=1), hepatic flexure (n=3), and ascending colon (n=2). Technical success was achieved in all the 42 patients (100%). The mean time of operation was (11.8±10.4) min (range 1.1-51.0 min). No serious procedure-related complication occurred. Minor bleeding occurred in 3 cases (7.1%). One patient died on the second day after surgery because of heart failure.
CONCLUSIONSColonoscopy-guided placement of self-expandable metallic stents without fluoroscopic monitoring in emergence management for acute malignant colorectal obstruction is effective and safe with shorter operative time.
Adult ; Aged ; Aged, 80 and over ; Colonoscopy ; Colorectal Neoplasms ; complications ; Female ; Humans ; Intestinal Obstruction ; etiology ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Stents
8.Association of tumor budding with clinicopathological characteristics and prognosis in T2 rectal cancer.
Jian-xiang HE ; Hao WANG ; Chuan-gang FU ; Rong-gui MENG ; Lian-jie LIU ; Wei ZHANG ; En-da YU
Chinese Journal of Gastrointestinal Surgery 2012;15(4):363-366
OBJECTIVETo demonstrate the association of tumor budding with clinicopathological features and prognosis in T2 rectal cancer.
METHODSClinicopathological data of 123 patients who underwent potentially curative resection for T2 rectal carcinoma between 2001 and 2005 at the Changhai Hospital were collected. All pathology slides were stained with hematoxylin and eosin for microscopic examinations. The maximum value of tumor buds(MV) and average value of tumor buds(AV) were calculated, which were classified as low value (≤5), median value (5 < bud value < 10), and high value (≥10).
RESULTSUnivariate analysis and multivariate analysis revealed that MV(P=0.000), AV(P=0.001), and lymphatic invasion (P=0.006) were independent predictors for lymph node metastasis in T2 rectal cancer. Neural invasion and poorly differentiation were significantly associated with MV(P<0.05). Neural invasion, vascular invasion and poorly differentiation were were significantly associated to AV (P<0.01). Disease-free survival (DFS) of patients with low AV, median AV and high AV was 110.5 months, 95.8 months, and 60.0 months respectively. There were significance differences in DFS of low AV with median and high AV(P<0.05). DFS of patients with low MV, median MV and high MV was 115.1 months, 98.5 months, and 86.0 months respectively. There were significance differences in DFS between low and high AV, and median and high MV(P<0.01 and P<0.05), while no significant difference existed between low and median MV.
CONCLUSIONTumor budding is a useful marker to indicate high invasiveness of rectal cancer and a valuable prognostic predictor.
Female ; Humans ; Lymphatic Metastasis ; Male ; Prognosis ; Rectal Neoplasms ; pathology ; surgery
9.Colonoscopic restoration for sigmoid vovulus in the elderly.
Zheng LOU ; En-da YU ; Rong-gui MENG ; Wei ZHANG ; Lian-jie LIU ; Han-tao WANG ; Chuan-gang FU
Chinese Journal of Gastrointestinal Surgery 2012;15(12):1244-1246
OBJECTIVETo investigate the emergency therapeutic strategy for sigmoid vovulus in the elderly.
METHODSClinical data of 14 elderly patients with sigmoid vovulus were analyzed retrospectively.
RESULTSThe mean age was(79.1±7.2) years(range, 70-93), and 11 patients (78.6%) were male. Emergency decompression and restoration with colonoscopy was performed in all the patients with a success rate of 100%. No patient required emergent surgery. Four patients(28.6%) recurred and they were managed well by repeat colonoscopic restoration.
CONCLUSIONEmergency colonoscopic restoration is the first treatment of choice for sigmoid vovulus in the elderly because it is safe and effective, and can be performed repeatedly.
Aged ; Aged, 80 and over ; Colon, Sigmoid ; surgery ; Colonoscopy ; Decompression, Surgical ; Emergencies ; Female ; Humans ; Intestinal Volvulus ; surgery ; Male ; Recurrence ; Retrospective Studies
10.A study of proximal humerus fractures using close reduction and percutaneous minimally invasive fixation.
Yin-wen LIU ; Yong KUANG ; Xin-feng GU ; Yu-xin ZHENG ; Zhi-qiang LI ; Xiao-en WEI ; Wei-da LU ; Hong-sheng ZHAN ; Yin-yu SHI
China Journal of Orthopaedics and Traumatology 2011;24(11):949-951
OBJECTIVETo investigate the clinical effects of close reduction and percutaneous minimally invasive fixation in the treatment of proximal humerus fractures.
METHODSFrom April 2008 to March 2010, 28 patients with proximal humerus fracture were treated with close reduction and percutaneous minimally invasive fixation. There were 21 males and 7 females, ranging in age from 22 to 78 years,with an average of 42.6 years. The mean time from suffering injuries to the operation was 1.7 d. Nineteen cases caused by falling down, 9 cases by traffic accident. The main clinical manifestation was swelling, pain and limited mobility of shoulders. According to Neer classification, two part fractures were in 17 cases and three part fractures in 11 cases. The locking proximal humerus plate was used to minimally fixation through deltoid muscle under acromion. The operating time,volume of blood loss, the length of incision and Constant-Murley assessment were applied to evaluate the therapeutic effects.
RESULTSThe mean operating time was 40 min, the mean blood loss was 110 ml, and the mean length of incision was about 5.6 cm. The postoperative X-ray showed excellent reduction and the plate and screws were successfully place. Twenty-eight patients were followed up for 6 to 24 months (averaged 14.2 months). The healing time ranged from 6 to 8 weeks and all incision was primarily healed. There were no cases with necrosis head humerus, 24 cases without omalgia, and 4 cases with o-malgia occasionally. All the patients can complete the daily life. The mean score of Constant-Murley assessment was 91.0 +/- 5.8, 24 cases got an excellent result, 3 good and 1 fair.
CONCLUSIONClose reduction and percutaneous minimally invasive fixation, not only can reduce surgical invasive, but also guarantee the early function activities. It has the advantages of less invasive, fixed well and less damage of blood circulation.
Adult ; Aged ; Female ; Fracture Healing ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; methods ; Shoulder Fractures ; physiopathology ; surgery

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