1.The expression of System Xc-/ GSH / GPX4 ferroptosis pathway in peripheral blood mononuclear cells of rheumatoid arthritis patients and its effect on the secretion of inflammatory factors
Can Liu ; Wukai Ma ; Changming Chen ; Yang An ; Zong Jiang ; Hai Huang
Acta Universitatis Medicinalis Anhui 2024;59(1):64-70
Objective :
To investigate the expression of genes and proteins in the peripheral blood mononuclear cell ( PBMC) cystine / glutamate antiporter system (System Xc-) / glutathione ( GSH) / glutathione peroxidase 4 ( GPX4) ferroptosis pathway and its influence on inflammatory factors in patients with rheumatoid arthritis ( RA) .
Methods :
30 patients with RA and 30 healthy participants were enrolled.PBMCs were isolated using Ficoll-hypaque density gradient centrifugation.The cells were categorized into the healthy control,RA,ferroptosis inhibitor,ferroptosis in- ducer group.The cell viability was checked using the cell counting kit-8 ( CCK-8) method.Intracellular Fe2 + rela- tive fluorescence intensity and reactive oxygen species (ROS) levels were detected using the FerroOrange and Di- hydroethidium (DHE) fluorescent probes,respectively.Western blot and real-time quantitative PCR (qPCR) de- tected the expression of nuclear factor erythroid 2-related factor 2 ( Nrf2 ) ,solute carrier family 7 member 11 (SLC7A11) ,GPX4 proteins and mRNA.And the flow cytometry quantified the levels of tumor necrosis factor α (TNF-α) ,Interleukin (IL) -1,and IL-6 in the supernatant of each cell group.
Results :
Compared to the healthy control group,the RA group showed a significantly increased Fe2 + concentration and elevated ROS levels,reduced expression of Nrf2,SLC7A11 and GPX4 proteins and mRNA,and increased contents of TNF-α , IL-1 and IL-6 in PBMC supernatant,and the differences were statistically significant.The concentration of Fe2 + and ROS levels in the inhibitor group were lower than those in the RA group,the proteins expressions of Nrf2,SLC7A11 and GPX4 increased,the mRNA expressions of SLC7A11 and GPX4 increased,the content of IL-6 in the PBMC supernatant decreased but the content of TNF-α increased,and the differences were statistically significant.In contrast,the in- ducer group,when compared to the RA group,displayed increased ROS levels,reduced expression of SLC7A11 protein and mRNA and decreased expression of Nrf2 protein,and the contents of TNF-α and IL-1 in the PBMC su- pernatant increased,but the expression of GPX4 protein increased ,and the differences were statistically signifi- cant.The inducer group,compared to the RA group,showed increased cell viability,and the difference was statis-
tically significant (P<0. 000 1) .
Conclusion
The presence of ferroptosis in PBMC in RA patients,inhibiting or inducing PBMC ferroptosis in RA patients,will inhibit or promote the secretion of inflammatory factors.Inhibition of PBMC ferroptosis in RA patients may be helpful in the treatment of RA.
2.Expert consensus on surgical treatment of oropharyngeal cancer
China Anti-Cancer Association Head and Neck Oncology Committee ; China Anti-Cancer Association Holistic Integrative Oral Cancer on Preventing and Screen-ing Committee ; Min RUAN ; Nannan HAN ; Changming AN ; Chao CHEN ; Chuanjun CHEN ; Minjun DONG ; Wei HAN ; Jinsong HOU ; Jun HOU ; Zhiquan HUANG ; Chao LI ; Siyi LI ; Bing LIU ; Fayu LIU ; Xiaozhi LV ; Zheng-Hua LV ; Guoxin REN ; Xiaofeng SHAN ; Zhengjun SHANG ; Shuyang SUN ; Tong JI ; Chuanzheng SUN ; Guowen SUN ; Hao TIAN ; Yuanyin WANG ; Yueping WANG ; Shuxin WEN ; Wei WU ; Jinhai YE ; Di YU ; Chunye ZHANG ; Kai ZHANG ; Ming ZHANG ; Sheng ZHANG ; Jiawei ZHENG ; Xuan ZHOU ; Yu ZHOU ; Guopei ZHU ; Ling ZHU ; Susheng MIAO ; Yue HE ; Jugao FANG ; Chenping ZHANG ; Zhiyuan ZHANG
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(11):821-833
With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth>3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.
3.Microbiomes combined with metabolomics reveals the changes of microbial and metabolic profile of articular cavity effusion in rheumatoid arthritis, urarthritis and osteoarthritis patients
Hanzhi Yi ; Wukai Ma ; Minhui Wang ; Chunxia Huang ; Guangzhao Gu ; Dan Zhu ; Hufan Li ; Can Liu ; Fang Tang ; Xueming Yao ; Liping Sun ; Nan Wang ; Changming Chen
Acta Universitatis Medicinalis Anhui 2024;59(12):2237-2245
Objective:
To investigate the changes of microorganisms and metabolites in joint effusion of patients with Rheumatoid arthritis(RA), Osteoarthritis(OA) and Urarthritis(UA). To provide new ideas for the study of the effect of microbiota on the pathogenesis of arthritis.
Methods:
Joint effusion samples were collected from 20 patients with RA, 20 patients with OA, and 20 patients with UA. 16S rRNA gene sequencing and untargeted ultra-high performance Liquid chromatography-mass spectrometry(LC-MS) were used to explore the differences in microorganisms and metabolites among the three groups. Pearson correlation analysis was used to detect the correlation between effusion microbiota and metabolites.
Results:
There were differences in microbial diversity and microbiota composition among the three groups. Combined with VIP>1 from OPLS-DA andP<0.05 from two-tailed Students t-test, 45 differential metabolites(Between RA and OA groups), 38 differential metabolites(Between UA and OA groups) and 16 differential metabolites(Between RA and UA groups), were identified. GO analysis and KEGG pathway analysis showed that the differential metabolic pathways among the three groups were mainly concentrated in citric acid cycle(TCA cycle), nucleotide metabolism, amino acid metabolism and glycolysis pathway. Correlation analysis of joint effusion microbiota and metabolites suggested that bacteria enriched in the three groups of joint effusion, such asPrevotella,Clostridium ruminosus,Prevotellaceae_UCG-001, were related to many key metabolites such as lysozyme, uric acid, glucose, and L-glutamine.
Conclusion
This study shows that there are a variety of bacterial flora in joint cavity effusion of RA, OA, and UA patients, and the differential metabolites produced by them are involved in the pathogenesis of the three types of arthritis by affecting a variety of metabolic pathways.
4.Construction of secretory IgA against SARS-CoV-2 and its biodistribution through nasal administration in mice
Ping HUANG ; Guanying ZHANG ; Xiangyang CHI ; Hancong SUN ; Ting FANG ; Changming YU ; Wei CHEN
Military Medical Sciences 2024;48(7):501-508
Objective To construct secretory IgA(sIgA)based on the previously screened IgG neutralizing antibody ZW2G10 against SARS-CoV-2,evaluate its activity and find out about the biodistribution of sIgA in ICR mice after nasal administration.Methods After expression,purification,and identification,sIgA was evaluated for its binding and neutralizing activity through ELISA and pseudovirus-based neutralization assays.SIgA was coupled with Alexa Fluor 750 dye and administered to mice via nasal administration.In vivo imaging was used to observe the biodistribution of sIgA.After dissection of the mice,the biodistribution of sIgA in various tissues and organs was observed.Results Compared with IgG,sIgA retained the binding ability to SARS-CoV-2 S proteins,and its neutralizing ability was enhanced.After nasal administration of a single dose of 1 mg/kg,sIgA could be retained in the lungs of mice for more than 72 hours.SIgA could be detected only in the nasal cavity and gastrointestinal tract within 8 h of administration,but not in the heart,liver,kidney,spleen,brain,bladder or blood.Conclusion In this study,a universal and efficient sIgA expression system has been established.sIgA can effectively target the respiratory tract and lungs after nasal administration.SIgA is expected to become a potential drug that provides immediate passive immune protection.
5.Application and practice of indocyanine green-guided laparoscopic radical gastrec-tomy for gastric cancer
Huang CHANGMING ; Liang HAN ; Zheng CHAOHUI ; Chen QIYUE ; Zhong QING ; Qiu TAOYUAN
Chinese Journal of Clinical Oncology 2024;51(13):663-669
Indocyanine green(ICG)near-infrared imaging technology has significant research value in laparoscopic radical gastrectomy and has garnered widespread attention and research both domestically and internationally.However,the application of ICG near-infrared ima-ging technology in laparoscopic radical gastrectomy is still in the exploratory stage in current clinical practice,with no unified standards es-tablished as yet.This review introduces the mechanism of ICG fluorescence imaging and discusses the indications and contraindications of ICG use in laparoscopic radical gastrectomy.The application methods and procedures of ICG molecular fluorescence imaging technology in laparoscopic radical gastrectomy and its clinical applications are elaborated upon.Finally,the practical applications of ICG-guided laparo-scopic radical gastrectomy is summarized and generalized to help facilitate its promotion and further standardization.
6.Advances in minimally invasive surgery for locally advanced gastric cancer
Yao ZIHAO ; Zhong QING ; Wu DONG ; Huang CHANGMING
Chinese Journal of Clinical Oncology 2024;51(13):690-694
Gastric cancer(GC)is one of the most common malignancies worldwide.In our country,the majority of patients are diagnosed with GC at alocally advanced stage.Fortunately,clinical studies have demonstrated that minimally invasive radical gastrectomy,particularly laparoscopic surgery,is just as effective as traditional open surgery in terms of both short-and long-term outcomes.Consequently,minim-ally invasive surgery has become the primary surgical approach for patients with locally advanced gastric cancer(LAGC).Advancements in surgical techniques and technologies are enabling even more precise and minimally invasive approaches to GC surgery.Based on recent do-mestic and international studies,this study aimed to review and elaborate on the development of minimally invasive surgery for LAGC.
7.Quality control of gastric resection range in laparoscopic locally advanced gastric cancer
Hualong ZHENG ; Linghua WEI ; Jun LU ; Changming HUANG
Chinese Journal of Gastrointestinal Surgery 2024;27(2):143-147
After nearly 30 years of exploration and practice, minimally invasive surgical techniques represented by laparoscopic technology have become an important means for the surgical treatment of gastric cancer. In China, laparoscopic radical resection for locally advanced gastric cancer has been extensively carried out. However, there are still controversies regarding the gastric resection range and methods for advanced gastric cancer. By reviewing relevant domestic and foreign guideline documents and combining team practice experience, this article elaborates on the key points of quality control of laparoscopic gastric resection range for locally advanced gastric cancer from aspects such as tumor localization and gastric resection range for upper, middle and lower gastric tumors. It aims to provide reference for carrying out and promoting laparoscopic radical gastrectomy more safely.
8.Recurrence outcomes of robotic-versus laparoscopic-assisted gastrectomy for gastric cancer: a multi-center propensity score-matched cohort study
Jun LU ; Taiyuan LI ; Li ZHANG ; Junjun SHE ; Junyu CHEN ; Qing ZHONG ; Zukai WANG ; Changming HUANG ; Chaohui ZHENG
Chinese Journal of Gastrointestinal Surgery 2024;27(8):799-807
Objective:To compare and evaluate recurrence patterns after robotic-assisted gastrectomy (RAG) versus laparoscopic-assisted gastrectomy (LAG).Methods:This was a retrospective cohort study of 2915 consecutive patients with gastric adenocarcinoma confirmed by postoperative histology as T1-4aN0-3M0, who had undergone minimally invasive radical gastrectomy at four large gastric cancer treatment centers (Fujian Medical University Union Hospital: 1426 patients; the First Affiliated Hospital, Nanchang University: 1108; Tianjin Medical University Cancer Institute and Hospital: 196; and First Affiliated Hospital of Xi'an Jiaotong University: 185 cases) between 1 January 2015 and 30 June 2019. 930 patients had undergone RAG (RAG group) and 1985 had undergone LAG (LAG group). We assessed the following characteristics: age, sex, body mass index, American Society of Anesthesiologists score, comorbidities, tumor size, extent of surgery, extent of lymph node dissection, pT, pN, year of surgery, and adjuvant chemotherapy, after propensity score matching (1:1). There were no significant differences in baseline clinical characteristics between the two groups formed by propensity score matching (837 in each group) (all P>0.05). The 3-year recurrence-free survival (RFS), recurrence pattern, and conditional RFS were compared. Results:We detected no significant differences in the overall recurrence rate at 3 years (128/837 [15.3%] vs. 141/837 [16.8%], P=0.387) or time to recurrence (15.7±8.1 months vs. 16.4±8.4 months, P=0.449) between the RAG and LAG groups. Peritoneal recurrence was the most common type of recurrence in both groups (55 [6.6%] vs. 69 [8.2%], P=0.524). The difference in 3-year RFS between the RAG and LAG groups was not statistically significant (83.2% vs. 82.5%, P=0.781). We found that age > 60 years, total gastrectomy, and worse pT stage and pN stage were independent risk factors for recurrence in the study patients (all P<0.05), whereas the surgical procedure (RAG or LAG) was not an independent risk factor for RFS ( P=0.242). The 3-year conditional RFS at various time points was comparable between the two groups (1 year postoperatively: 84.6% vs. 84.7%, P=0.793; 3 years postoperatively: 91.5% vs. 94.9%, P=0.647). Conclusions:In this multicenter study of patients with locally resectable gastric cancer, we demonstrated that RAG performed by surgeons at large gastric cancer centers is not inferior to LAG in 3-year recurrence rate or recurrence patterns.
9.Prognostic significance of textbook outcome in advanced gastric patients who underwent neoadjuvant chemotherapy followed by surgical resection
Yihui TANG ; Zening HUANG ; Qiyue CHEN ; Ping LI ; Jianwei XIE ; Jiabin WANG ; Jianxian LIN ; Jun LU ; Longlong CAO ; Mi LIN ; Ruhong TU ; Chaohui ZHENG ; Changming HUANG
Chinese Journal of Surgery 2024;62(5):379-386
Objective:To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection.Methods:This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group ( n=168) and the non-TO group ( n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score ( OR=0.488, 95% CI: 0.278 to 0.856, P=0.012) and ypN stage ( OR=0.626, 95% CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS ( HR=0.662, 95% CI: 0.457 to 0.959, P=0.029) and DFS ( HR=0.687, 95% CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion:TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.
10.Quality control of gastric resection range in laparoscopic locally advanced gastric cancer
Hualong ZHENG ; Linghua WEI ; Jun LU ; Changming HUANG
Chinese Journal of Gastrointestinal Surgery 2024;27(2):143-147
After nearly 30 years of exploration and practice, minimally invasive surgical techniques represented by laparoscopic technology have become an important means for the surgical treatment of gastric cancer. In China, laparoscopic radical resection for locally advanced gastric cancer has been extensively carried out. However, there are still controversies regarding the gastric resection range and methods for advanced gastric cancer. By reviewing relevant domestic and foreign guideline documents and combining team practice experience, this article elaborates on the key points of quality control of laparoscopic gastric resection range for locally advanced gastric cancer from aspects such as tumor localization and gastric resection range for upper, middle and lower gastric tumors. It aims to provide reference for carrying out and promoting laparoscopic radical gastrectomy more safely.


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