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1.
Article En | MEDLINE | ID: mdl-38652608

Human activity recognition has played a crucial role in healthcare information systems due to the fast adoption of artificial intelligence (AI) and the internet of thing (IoT). Most of the existing methods are still limited by computational energy, transmission latency, and computing speed. To address these challenges, we develop an efficient human activity recognition in-memory computing architecture for healthcare monitoring. Specifically, a mechanism-oriented model of Ag/a-Carbon/Ag memristor is designed, serving as the core circuit component of the proposed in-memory computing system. Then, one-transistor-two-memristor (1T2M) crossbar array is proposed to perform high-efficiency multiply-accumulate (MAC) operation and high-density memory in the proposed scheme. To facilitate understanding of the proposed efficient human activity recognition in-memory computing design, self-attention ConvLSTM module, multi-head convolutional attention module, and recognition module are proposed. Furthermore, the proposed system is applied to perform human activity recognition, which contains eleven different human activities, including five different postural falls, and six basic daily activities. The experimental results show that the proposed system has advantages in recognition performance (≥ 0.20% accuracy, ≥ 1.10% F1-score) and time consumption (approximately 8∼10 times speed up) compared to existing methods, indicating an advancement in smart healthcare applications.

2.
Surg Endosc ; 38(4): 1912-1921, 2024 Apr.
Article En | MEDLINE | ID: mdl-38326587

BACKGROUND: Many patients experience anorectal dysfunction after rectal surgery, which is known as low anterior resection syndrome (LARS). Robotic systems have many technical advantages that may be suitable for functional preservation after low rectal resection. Thus, the study aimed to explore whether robotic surgery can reduce the incidence and severity of LARS. METHODS: Patients undergoing minimally invasive sphincter-sparing surgery for low rectal cancer were enrolled between January 2015 and December 2020. The patients were divided into robotic or laparoscopic groups. The LARS survey was conducted at 6, 12 and 18 months postoperatively. Major LARS scores were analysed as the primary endpoint. In order to reduce confounding factors, one-to-two propensity score matches were used. RESULTS: In total, 342 patients were enrolled in the study. At 18 months postoperatively, the incidence of LARS was 68.7% (235/342); minor LARS was identified in 112/342 patients (32.7%), and major LARS in 123/342 (36.0%). After matching, the robotic group included 74 patients, and the laparoscopic group included 148 patients. The incidence of major LARS in the robotic group was significantly lower than that in the laparoscopic group at 6, 12, and 18 months after surgery. In multivariate logistic regression analysis, tumour location, laparoscopic surgery, intersphincteric resection, neoadjuvant therapy, and anastomotic leakage were independent risk factors for major LARS after minimally invasive sphincter-sparing surgery for low rectal cancer. Furthermore, a major LARS prediction model was constructed. Results of model evaluation showed that the nomogram had good prediction accuracy and efficiency. CONCLUSIONS: Patients with low rectal cancer may benefit from robotic surgery to reduce the incidence and severity of LARS. Our nomogram could aid surgeons in setting an individualized treatment program for low rectal cancer patients.


Rectal Neoplasms , Robotic Surgical Procedures , Humans , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Robotic Surgical Procedures/adverse effects , Low Anterior Resection Syndrome , Anal Canal/surgery , Anal Canal/pathology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Propensity Score , Organ Sparing Treatments
3.
Nat Commun ; 15(1): 427, 2024 Jan 10.
Article En | MEDLINE | ID: mdl-38199995

The microbiome in a specific human organ has been well-studied, but few reports have investigated the multi-organ microbiome as a whole. Here, we aim to analyse the intra-individual inter-organ and intra-organ microbiome in deceased humans. We collected 1608 samples from 53 sites of 7 surface organs (oral cavity, esophagus, stomach, small intestine, appendix, large intestine and skin; n = 33 subjects) and performed microbiome profiling, including 16S full-length sequencing. Microbial diversity varied dramatically among organs, and core microbial species co-existed in different intra-individual organs. We deciphered microbial changes across distinct intra-organ sites, and identified signature microbes, their functional traits, and interactions specific to each site. We revealed significant microbial heterogeneity between paired mucosa-lumen samples of stomach, small intestine, and large intestine. Finally, we established the landscape of inter-organ relationships of microbes along the digestive tract. Therefore, we generate a catalogue of bacterial composition, diversity, interaction, functional traits, and bacterial translocation in human at inter-organ and intra-organ levels.


Appendix , Microbiota , Humans , Bacterial Translocation , Stomach , Microbiota/genetics , Mouth
4.
Surg Today ; 54(3): 220-230, 2024 Mar.
Article En | MEDLINE | ID: mdl-37468743

PURPOSE: Robotic lateral lymph node dissection (LLND) has been described as a safe and feasible procedure for local advanced rectal cancer. The aim of this study was to evaluate the learning curve for robotic-assisted LLND. METHODS: We collected data on 78 consecutive patients who underwent robotic-LLND at our hospital. The learning curve was analyzed using the cumulative sum (CUSUM) method to assess changes in the unilateral LLND operative times across the case sequence. RESULTS: Among the 78 patients, 52 underwent bilateral LLND and 26 underwent unilateral LLND. A total of 130 consecutive data were recorded. We arranged unilateral robotic-LLND operative times and calculated cumulative sum values, allowing the differentiation of three phases: phase I (learning period, cases 1-51); phase II (proficiency period, cases 52-83); and phase III (mastery period, cases 84-130). As the learning curve accumulated, the operation time and estimated blood loss of unilateral robotic-LLND decreased significantly with each phase (P < 0.05). By 12 months after surgery, the International Prostatic Symptom Score of patients at phase III was significantly lower than at phase I (P < 0.05). CONCLUSION: The CUSUM curve shows three phases in the learning of robotic-LLND. The estimated learning curve for robotic-assisted rectal-LLND is achieved after 51 cases.


Laparoscopy , Rectal Neoplasms , Robotic Surgical Procedures , Humans , Robotic Surgical Procedures/methods , Laparoscopy/methods , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Lymph Node Excision/methods , Rectum/surgery , Lymph Nodes/pathology , Learning Curve , Retrospective Studies , Neoplasm Recurrence, Local/surgery
5.
Hum Cell ; 37(1): 345-355, 2024 Jan.
Article En | MEDLINE | ID: mdl-37938540

Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive and recurrent soft tissue sarcoma. It most commonly occurs secondary to neurofibromatosis type I, and it has a 5-year survival rate of only 8-13%. To better study the tumor heterogeneity of MPNST and to develop diverse treatment options, more tumor-derived cell lines are needed to obtain richer biological information. Here, we established a primary cell line of relapsed MPNST RsNF cells derived from a patient diagnosed with NF1 and detected the presence of NF1 mutations and SUZ12 somatic mutations through whole-exome sequencing(WES). Through tumor molecular marker targeted sequencing and single-cell transcriptome sequencing, it was found that chromosome 7 copy number variation (CNV) was gained in this cell line, and ZNF804B, EGFR, etc., were overexpressed on chromosome 7. Therefore, RsNF cells can be used as a useful tool in NF1-associated MPNST genomic amplification studies and to develop new therapeutic strategies.


Neurofibromatosis 1 , Neurofibrosarcoma , Humans , Neurofibrosarcoma/genetics , Neurofibrosarcoma/therapy , Neurofibrosarcoma/complications , DNA Copy Number Variations/genetics , Neurofibromatosis 1/genetics , Neurofibromatosis 1/therapy , Neurofibromatosis 1/complications , Mutation , Cell Line, Tumor
6.
Sci Rep ; 13(1): 14866, 2023 09 08.
Article En | MEDLINE | ID: mdl-37684265

Treatment guidelines for colorectal cancer (CRC) in elderly patients remain unclear. This study aimed to investigate whether elderly patients (≥ 70 years) with CRC benefit from surgery and adjuvant therapy. A total of 90,347 eligible CRC patients older than 70 years were collected from the Surveillance, Epidemiology, and End Results (SEER) database and divided into a surgery group and a no-surgery group. After being matched by propensity score matching at a 1:1 ratio, 23,930 patients were included in our analysis. The Kaplan‒Meier method and log-rank test were applied to compare overall survival (OS) and cancer-specific survival (CSS). Univariate and multivariate Cox regression analyses were utilized to confirm independent prognostic factors for OS and CSS. In age-stratified analysis (70-74; 75-79; 80-84; ≥ 85), the OS and CSS rates of patients in the surgery group were significantly higher than those of patients in the no-surgery group (all P < 0.001). Adjuvant therapy was an independent prognostic factor for OS and CSS in elderly patients with CRC (all P < 0.001). Further analysis showed that elderly colon cancer patients with stage III and stage IV disease gained a survival benefit from adjuvant chemotherapy. Adjuvant chemoradiotherapy can significantly improve OS and CSS in elderly rectal cancer patients with stage II, III, and IV disease. In conclusion, among CRC patients aged ≥ 70 years reported in the SEER database, treatment with surgical resection is significantly associated with improved OS and CSS. Moreover, adjuvant therapy led to a significant prognostic advantage for elderly advanced CRC patients who underwent surgery.


Colonic Neoplasms , Colorectal Neoplasms , Aged , Humans , Combined Modality Therapy , Chemotherapy, Adjuvant , Chemoradiotherapy, Adjuvant , Colorectal Neoplasms/surgery
7.
Front Nutr ; 10: 1237047, 2023.
Article En | MEDLINE | ID: mdl-37671200

Objective: The assessment of nutritional status has been recognized as crucial in the treatment of geriatric cancer patients. The objective of this study is to determine the clinical predictive value of the geriatric nutritional risk index (GNRI) in predicting the short-term and long-term prognosis of elderly rectal cancer (RC) patients who undergo surgical treatment after neoadjuvant therapy. Methods: Between January 2014 and December 2020, the clinical materials of 639 RC patients aged ≥70 years who underwent surgical treatment after neoadjuvant therapy were retrospectively analysed. Propensity score matching was performed to adjust for baseline potential confounders. Logistic regression analysis and competing risk analysis were conducted to evaluate the correlation between the GNRI and the risk of postoperative major complications and cumulative incidence of cancer-specific survival (CSS). Nomograms were then constructed for postoperative major complications and CSS. Additionally, 203 elderly RC patients were enrolled between January 2021 and December 2022 as an external validation cohort. Results: Multivariate logistic regression analysis showed that GNRI [odds ratio = 1.903, 95% confidence intervals (CI): 1.120-3.233, p = 0.017] was an independent risk factor for postoperative major complications. In competing risk analysis, the GNRI was also identified as an independent prognostic factor for CSS (subdistribution hazard ratio = 3.90, 95% CI: 2.46-6.19, p < 0.001). The postoperative major complication nomogram showed excellent performance internally and externally in the area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analysis (DCA). When compared with other models, the competing risk prognosis nomogram incorporating the GNRI achieved the highest outcomes in terms of the C-index, AUC, calibration plots, and DCA. Conclusion: The GNRI is a simple and effective tool for predicting the risk of postoperative major complications and the long-term prognosis of elderly RC patients who undergo surgical treatment after neoadjuvant therapy.

8.
Front Physiol ; 14: 1175075, 2023.
Article En | MEDLINE | ID: mdl-37168230

Largemouth bass (LMB) production exceeded 0.7 million tons in 2021 and has become one of the most important freshwater aquaculture species in China. The stable and fixed culture cycle led to regular and drastic price fluctuation during the past decade. Strong price fluctuation provides opportunities and challenges for the LMB industry, and out-of-season spawning (OSS) and culture will provide technical support for the opportunities. To induce OSS at a low cost, we established a controllable recirculating system that allows precise thermo-photoperiod manipulation. In the system, four experimental groups were assigned, 18NP (18°C overwintering water temperature, natural photoperiod), 18CP (18°C overwintering water temperature, controlled photoperiod), 16CP (16°C overwintering water temperature, controlled photoperiod), and NTNP (natural water temperature and natural photoperiod), to determine the effects of chilling temperature and photoperiod on spawning performance. OSS was observed in all the experimental groups without significant differences, except NTNP. The manipulated broodstock can re-spawn 3 months later in the next spring in advance. Further analysis of the volume percentage of different stages of oocytes provides a base for excellent regression between the volume percentage of the primary growth stage, cortical alveoli stage, vitellogenesis/maturation stage, and gonadal development/maturation. The results suggest that the volume percentage of oocytes is a better indicator of gonadal development and maturation than the gonadosomatic index. We also found that LMB prefers palm fiber as a spawning nest over gravel. The findings of this work provide important technique guidance for practical OSS of the LMB aquaculture industry and standardization of ovary development and maturation in fish with asynchronous developmental oocytes.

9.
Clin Res Hepatol Gastroenterol ; 47(3): 102090, 2023 03.
Article En | MEDLINE | ID: mdl-36746236

BACKGROUND AND AIMS: The appendix has an important immune function in both health and disease, and appendectomy may influence microbial ecology and immune function. This meta-analysis aims to assess the association between appendectomy and the risk and course of Crohn's disease (CD). METHODS: PubMed, EMBASE, and the Cochrane Library were used to identify all studies published until June 2022. Data from studies evaluating the association between appendectomy and CD were reviewed. RESULTS: A total of 28 studies were included in the final analysis, comprising 22 case-control and 6 cohort studies. A positive relationship between prior appendectomy and the risk of developing CD was observed in both case-control studies (odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.22-2.08) and cohort studies (relative risk [RR]: 2.28, 95% CI: 1.66-3.14). The elevated risk of CD persisted 5 years post-appendectomy (RR = 1.24, 95% CI: 1.12-1.36). The risk of developing CD was similarly elevated regardless of the presence (RR = 1.64, 95% CI: 1.17-2.31) or absence (RR = 2.77, 95% CI: 1.84-4.16) of appendicitis in patients. Moreover, significant differences were found in the proportion of terminal ileum lesions (OR = 1.63; 95% CI: 1.38-1.93) and colon lesions (OR = 0.70; 95% CI: 0.5-0.84) between CD patients with appendectomy and those without appendectomy. CONCLUSIONS: The risk of developing CD following an appendectomy is significant and persists 5 years postoperatively. Moreover, the elevated risk of CD may mainly occur in the terminal ileum.


Appendix , Crohn Disease , Humans , Appendectomy , Cohort Studies , Case-Control Studies
10.
Surg Endosc ; 37(6): 4403-4413, 2023 06.
Article En | MEDLINE | ID: mdl-36757452

BACKGROUND: Lateral lymph node dissection (LLND) represents a technically challenging procedure. This study aimed to evaluate the perioperative, genitourinary functional and mid-term oncological outcomes of laparoscopic lateral lymph node dissection (LLLND) and robotic lateral lymph node dissection (RLLND) for advanced lower rectal cancer (ALRC). METHODS: Between January 2015 and April 2021, consecutive patients who underwent RLLND and LLLND at two high-volume centres were enrolled. The perioperative outcomes, genitourinary function recovery and mid-term oncological outcomes of the patients were compared. A subgroup analysis of patients who underwent neoadjuvant chemoradiotherapy (nCRT) was performed. RESULTS: A total of 205 patients were included in the analysis, with 95 in the RLLND group and 110 in the LLLND group. The patients in the RLLND group had a longer operative time, less blood loss, and more harvested internal iliac lymph nodes than did those in the LLLND group. In postoperative complication, urinary retention was less frequent in the RLLND group than in the LLLND group. Additionally, the RLLND group had better genitourinary function recovery. Similar results were also observed from the nCRT subgroup analysis. Moreover, there was no significant difference in mid-term oncological outcomes between the two groups. Further subgroup analysis indicated that the patients who underwent nCRT + LLLND/RLLND had better local control than those who underwent only LLLND/RLLND. CONCLUSIONS: RLLND is safe and feasible for ALRC and is associated with more harvested internal iliac lymph nodes and better genitourinary function recovery. NCRT combined with minimally invasive LLND could constitute an improved strategy for ALRC.


Laparoscopy , Rectal Neoplasms , Robotic Surgical Procedures , Humans , Retrospective Studies , Robotic Surgical Procedures/methods , Lymph Node Excision/methods , Lymph Nodes/surgery , Lymph Nodes/pathology , Laparoscopy/methods , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Treatment Outcome , Neoplasm Recurrence, Local/surgery
11.
Oncogene ; 42(7): 530-540, 2023 02.
Article En | MEDLINE | ID: mdl-36539569

Appendectomy impacts the homeostasis of gut microbiome in patients. We aimed to study the role of appendectomy in colorectal cancer (CRC) risk through causing gut microbial dysbiosis. Population-based longitudinal study (cohort 1, n = 129,155) showed a 73.0% increase in CRC risk among appendectomy cases throughout 20 years follow-up (Adjusted sub-distribution hazard ratio (SHR) 1.73, 95% CI 1.49-2.01, P < 0.001). Shotgun metagenomic sequencing was performed on fecal samples from cohort 2 (n = 314). Gut microbial dysbiosis in appendectomy subjects was observed with significant enrichment of 7 CRC-promoting bacteria (Bacteroides vulgatus, Bacteroides fragilis, Veillonella dispar, Prevotella ruminicola, Prevotella fucsa, Prevotella dentalis, Prevotella denticola) and depletion of 5 beneficial commensals (Blautia sp YL58, Enterococcus hirae, Lachnospiraceae bacterium Choco86, Collinsella aerofaciens, Blautia sp SC05B48). Microbial network analysis showed increased correlation strengths among enriched bacteria and their enriched oncogenic pathways in appendectomy subjects compared to controls. Of which, B. fragilis was the centrality in the network of the enriched bacteria. We further confirmed that appendectomy promoted colorectal tumorigenesis in mice by causing gut microbial dysbiosis and impaired intestinal barrier function. Collectively, this study revealed appendectomy-induced microbial dysbiosis characterized by enriched CRC-promoting bacteria and depleted beneficial commensals, signifying that the gut microbiome may play a crucial role in CRC development induced by appendectomy.


Colorectal Neoplasms , Gastrointestinal Microbiome , Animals , Mice , Gastrointestinal Microbiome/genetics , Dysbiosis/microbiology , Appendectomy/adverse effects , Longitudinal Studies , Colorectal Neoplasms/genetics , Colorectal Neoplasms/microbiology
12.
Front Oncol ; 12: 1024467, 2022.
Article En | MEDLINE | ID: mdl-36568209

Background: The effects of laterality of the primary tumor on survival in patients in different stages of colon cancer are contradictory. We still lack a strictly evaluated and validated survival prediction tool, considering the different roles of tumor laterality in different stages. Methods: A total of 101,277 and 809 colon cancer cases were reviewed using the Surveillance, Epidemiology, and End Results database and the First Affiliated Hospital of Xi 'an Jiaotong University database, respectively. We established training sets, internal validation sets and external validation sets. We developed and evaluated stage-specific prediction models and unified prediction models to predict cancer-specific survival and compared the prediction abilities of these models. Results: Compared with right-sided colon cancers, the risk of cancer-specific death of left-sided colon cancer patients was significantly higher in stage I/II but was markedly lower in stage III patients. We established stage-specific prediction models for stage I/II and stage III separately and established a unified prediction model for all stages. By evaluating and validating the validation sets, we reported high prediction ability and generalizability of the models. Furthermore, the stage-specific prediction models had better predictive power and efficiency than the unified model. Conclusions: Right-sided colon cancer patients have better cancer-specific survival than left-sided colon cancer patients in stage I/II and worse cancer-specific survival in stage III. Using stage-specific prediction models can further improve the prediction of cancer-specific survival in colon cancer patients and guide clinical decisions.

13.
Front Oncol ; 12: 930942, 2022.
Article En | MEDLINE | ID: mdl-35880161

Background: The preoperative prediction of lateral pelvic lymph node (LPLN) metastasis is crucial in determining further treatment strategies for advanced lower rectal cancer patients. In this study, we established a nomogram model to preoperatively predict LPLN metastasis and then externally validated the accuracy of this model. Methods: A total of 287 rectal cancer patients who underwent LPLN dissection were included in this study. Among them, 200 patients from the Peking University First Hospital were included in the development set, and 87 patients from the First Affiliated Hospital of Xi'an Jiaotong University were included in the independent external validation set. Multivariate logistic regression analysis was used to develop the nomogram. The performance of the nomogram was assessed based on its calibration, discrimination, and clinical utility. Results: Five factors (differentiation grade, extramural vascular invasion, distance of the tumor from the anal verge, perirectal lymph node status, and largest short-axis diameter of LPLN) were identified and included in the nomogram. The nomogram developed based on the analysis showed robust discrimination with an area under the receiver operating characteristic curve (AUC) of 0.878 (95% CI, 0.824-0.932). The validation set showed good discrimination with an AUC of 0.863 (95% CI, 0.779-0.948). Decision curve analysis showed that the nomogram was clinically useful. Conclusions: The present study proposed a clinical-imaging nomogram with a combination of clinicopathological risk factors and imaging features. After external verification, the predictive power of the nomogram model was satisfactory, and it is expected to be a convenient, visual, and personalized clinical tool for assessing the risk of LPLN metastasis in advanced lower rectal cancer patients.

14.
J Vis Exp ; (180)2022 02 12.
Article En | MEDLINE | ID: mdl-35225257

Since their approval for clinical use, da Vinci surgical robots have shown great advantages in gastrointestinal surgical operations, especially in complex procedures. The high-quality 3-D visual, multijoint arm and natural tremor filtration allow the surgeon to expose and dissect more accurately with minimal invasion. Total mesorectal excision is the standard surgical technique for the treatment of resectable rectal cancer. To reduce the lateral recurrence rate, lateral pelvic lymph node dissection can be performed, as it is a safe and feasible procedure for locally advanced middle-low rectal cancer with a high possibility of metastasis to the lateral lymph nodes. However, the complexity of the anatomic structures and the high postoperative complication rate limit its application. Recently, several surgeons have increasingly used robotic techniques for total mesorectal excision and lateral pelvic lymph node dissection. Compared with open and laparoscopic surgery, the robotic technique has several advantages, such as less blood loss, fewer blood transfusions, minimal trauma, shorter postoperative hospitalization, and quicker recovery. A robotic approach is generally regarded as a reasonable alternative for complicated procedures such as lateral pelvic lymph node dissection, although there are a limited number of high-quality prospective randomized controlled studies reporting direct evidence. Here, we provide the detailed steps of robot-assisted total mesorectal excision and lateral pelvic lymph node dissection performed at the First Affiliated Hospital of Xi'an Jiaotong University.


Laparoscopy , Rectal Neoplasms , Robotics , Humans , Laparoscopy/methods , Lymph Node Excision/methods , Lymph Nodes/pathology , Prospective Studies , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Rectum/pathology , Treatment Outcome
16.
J Environ Psychol ; 79: 101745, 2022 Feb.
Article En | MEDLINE | ID: mdl-34908644

Essential workers such as medical workers and police officers are first-line fighters during public-health crises, such as COVID-19 pandemic. Every time, they are under heavy stress both physically and mentally. The goal of the present study was to develop a novel nature-based intervention to promote their well-being. A representative sample of essential workers in China was recruited for a five-day intervention program, and were randomly assigned to two groups. The experimental group watched 2-min video clips of natural scenes every day, while the control group watched urban scenes. Results indicated that after five days, the natural stimuli intervention yielded overall improvements in various indices of subjective well-being. Furthermore, analyses of nested longitudinal data confirmed that everyday nature stimuli exposure provided both immediate and repeated restorative benefits. The proposed natural-based intervention is brief and easy-to-use, offering a cost-efficient psychological booster to promote subjective well-being of essential workers during this crisis time.

17.
Front Oncol ; 11: 738300, 2021.
Article En | MEDLINE | ID: mdl-34692515

Patients with germline neurofibromatosis type 1 (NF1) microdeletions frequently exhibit hereditary syndromes such as cardiovascular anomalies and have an increased risk of malignant peripheral nerve sheath tumors (MPNSTs). This study aimed to identify the genes codeleted with SUZ12 that are related to MPNST. We used differential gene expression and enrichment analyses to analyze the SUZ12-mutant and SUZ12-wild-type gene expression profiles in the GSE118186 and GSE66743 datasets in Gene Expression Omnibus (GEO). PPI network analysis combined with MPNST patient survival analysis was used to identify ADCY1, which catalyzes the conversion of ATP to cAMP, as a key gene. Moreover, chromatin immunoprecipitation sequencing (ChIP-Seq) showed that the distribution of H3K27me3 in the ADCY1 promoter region and gene body was significantly reduced in SUZ12-mutant cells. To verify the role of ADCY1 in SUZ12 mutation, we used RNA interference and plasmid transfection to interfere with SUZ12 expression in plexiform neurofibroma (pNF) and MPNST cell lines and then treated the cells with forskolin, IBMX and H89. ERK phosphorylation was accelerated and prolonged after siRNA transfection, especially in ipNF05.5 cells, and the intensity and duration of ERK activation were reduced after SUZ12 overexpression. Importantly, the level of p-ERK was consistent with that of Rap1-GTP. Moreover, H89 completely blocked Rap1 activation and the changes in the p-ERK level after SUZ12 siRNA transfection. In conclusion, our findings suggested that SUZ12 loss potentiates the effects of NF1 mutations by amplifying Ras signaling through the ADCY1/cAMP/Rap1/ERK pathway and that SUZ12 may serve as a therapeutic and prognostic biomarker in NF1-associated neurofibromas.

18.
Molecules ; 26(13)2021 Jun 25.
Article En | MEDLINE | ID: mdl-34201944

Photodynamic therapy (PDT) as a safe, non-invasive modality for cancer therapy, in which the low oxygen and high glutathione in the tumor microenvironment reduces therapeutic efficiency. In order to overcome these problems, we prepared a supramolecular photosensitive system of O2-Cu/ZIF-8@ZIF-8@WP6-MB (OCZWM), which was loaded with oxygen to increase the oxygen concentration in the tumor microenvironment, and the Cu2+ in the system reacted with glutathione (GSH) to reduce the GSH concentration to generate Cu+. It is worth noting that the generated Cu+ can produce the Fenton reaction, thus realizing the combination therapy of PDT and chemodynamic therapy (CDT) to achieve the purpose of significantly improving the anti-cancer efficiency.


Neoplasms/drug therapy , Photochemotherapy , Photosensitizing Agents , Tumor Microenvironment/drug effects , Hep G2 Cells , Humans , Methylene Blue/chemistry , Neoplasms/metabolism , Neoplasms/pathology , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Quaternary Ammonium Compounds/chemistry
19.
Int J Radiat Oncol Biol Phys ; 111(3): 773-784, 2021 11 01.
Article En | MEDLINE | ID: mdl-34058257

PURPOSE: Interstitial brachytherapy based on phosphorus-32 (P-32) has an established role as a minimally invasive treatment modality for patients with cystic craniopharyngioma. However, reporting on long-term outcomes with toxicity profiles for large cohorts is lacking in the literature. The purpose of this study is therefore to evaluate the long-term visual, endocrinal, and neurocognitive functions in what is the largest patient series having received this treatment to date. METHODS AND MATERIALS: We retrospectively evaluated 90 patients with cystic craniopharyngiomas who were treated with stereotactic intracavitary brachytherapy between 1998 and 2010. Colloidal activity of injected radioisotope P-32 was based on an even distribution within the tumor. After treatment, patients were followed-up for a minimum of 5 years and over a mean of 121 months (60-192 months) to assess radiographic and clinical responses. RESULTS: The 90 patients included in our study cohort underwent a total of 108 stereotactic surgical procedures for 129 craniopharyngioma-related cysts. Of the included tumors, 65 (72.2%) were associated with a single cyst, 15 (16.7%) were associated with 2 cysts, and 10 (11.1%) tumors had developed septations with 3 to 4 cysts. Stereotactic cyst puncture and content aspiration were used to drain a mean cyst fluid volume of 21.4 mL (1.0-55.0 mL). Each cyst was then instilled for interstitial brachytherapy with colloidal P-32 solution. Based on radiographic follow-up assessments, 56 cysts (43.4%) showed resolution and/or nonrecurrence, which was classified as a complete response to treatment; 47 cysts (36.4%) showed a partial response; and 5 cysts (3.9%) displayed a stable appearance. Treatment resulted in immediate and clinically significant vision improvement in 54 of 63 (86%) symptomatic patients, and this improvement was maintained. Progression-free survival rates at 5 and 10 years were 95.5% and 84.4%, respectively. CONCLUSIONS: P-32-based interstitial brachytherapy can play an effective role in managing patients with cystic craniopharyngiomas. It can be considered a valid alternative to surgery in select patients with a favorable toxicity profile and long-term clinical outcomes.


Brachytherapy , Craniopharyngioma , Cysts , Pituitary Neoplasms , Brachytherapy/adverse effects , Craniopharyngioma/diagnostic imaging , Craniopharyngioma/radiotherapy , Cysts/radiotherapy , Humans , Phosphorus Radioisotopes , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/radiotherapy , Retrospective Studies
20.
Microbiol Res ; 244: 126652, 2021 Mar.
Article En | MEDLINE | ID: mdl-33310352

Actinobacteria that inhabit lichen symbionts are considered a promising yet previously underexplored source of novel compounds. Here, for the first time, we conducted a comprehensive investigation with regard to strain isolation and identification of lichen-associated actinobacteria from Tibet Plateau, antimicrobial activity screening, biosynthetic genes detection, bioactive metabolites identification and activity prediction. A large number of culturable actinomycetes were isolated from lichens around Qinghai Lake, in Qinghai-Tibet Plateau. Twenty-seven strains with distinct morphological characteristics were preliminarily studied. 16S rRNA gene identification showed that 13 strains were new species. The PCR-screening of specific biosynthetic genes indicated that these 27 isolates had abundant intrinsic biosynthetic potential. The antimicrobial activity experiment screened out some potential biological control antagonistic bacteria. The metabolites of 13 strains of Streptomyces with antibacterial activity were analyzed by LC-HRMS, and further 18 compounds were identified by NMR and / or LC-HRMS. The identified compounds were mainly pyrrolidine and indole derivatives, as well as anthracyclines. Seven compounds were identified with less biological activity, then predicted and evaluated their biological activity. The predicted results showed that compound 2 had excellent inhibitory activity on HIV-1 reverse transcriptase. Overall, the results indicate actinobacteria isolated from unexploited plateau lichen are promising sources of biological active metabolite, which could provide important bioactive compounds as potential antibiotic drugs.


Actinobacteria/metabolism , Anti-Infective Agents/metabolism , Anti-Infective Agents/pharmacology , Lichens/microbiology , Actinobacteria/chemistry , Actinobacteria/classification , Actinobacteria/genetics , Anti-Infective Agents/chemistry , Biodiversity , Chromatography, High Pressure Liquid , Lichens/physiology , Mass Spectrometry , Phylogeny , Symbiosis , Tibet
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