1.Mechanism of Action of Chinese Medicinal Herbs in the Treatment of Primary Myelofibrosis based on Bioinformatics and Molecular Dynamics
Jiayuan GUO ; Jile XIN ; Man ZHANG ; Mingxin LIU ; Jingwen LIU ; Yajing SU ; Huihui SHI ; Jue GUO ; Wenqing LIU ; Kailu WEI ; Yalin SONG ; Qiuling MA
Journal of Traditional Chinese Medicine 2024;65(21):2250-2258
ObjectiveTo explore the molecular mechanism implicated in the treatment of primary myelofibrosis (PMF) using Chinese medicinal herbs (CMH) by bioinformatics and molecular dynamics. MethodsData mining was performed to find the high-frequency CMH in treating PMF between the year of 1985 and 2024 by searching CNKI, Chinese Science and Technology Journal Database (CCD), and China Academic Journal Database (CSPD). TCMSP, SwissTargetPrediction and related reports were used to collect the main active ingredients of high-frequency CMH and their targets. The PMF datasets GSE44426 and GSE124281 were downloaded from GEO database, and R software was used for data normalization and differentially expressed genes (DEGs) screening. Key module hub genes were obtained by weighted gene co-expression network analysis (WGCNA) analysis. The common intersection genes of active ingredient targets, DEGs and key module hub genes of CMH were selected, and the target network was generated using Cytoscape 3.9.2 software. The core target network was generated by topological analysis, while key pathways were selected by GO and KEGG pathway enrichment analysis, and protein interaction relationships were obtained from the String database, so as to construct drug-ingredient-target network and protein interaction network (PPI) relationship diagrams. Discovery Studio 2020 software was used to perform molecular docking, and the GROMACS program was used to perform molecular dynamics simulation. ResultsA total of 21 prescriptions were collected involving 121 herbs. There were 9 herbs with a frequency ≥10 times, which were Danshen (Radix et Rhizoma Salviae Miltiorrhizae), Huangqi (Radix Astragali), Baizhu (Rhizoma Atractylodis Macrocephalae), Danggui (Radix Angelicae Sinensis), Dangshen (Radix Codonopsis), Gancao (Radix et Rhizoma Glycyrrhizae), Baishao (Radix Paeoniae Alba), Fuling (Poria) and Shudihuang (Radix Rehmanniae Praeparata) from high- to low-frequency. A total of 98 active ingredients and 1125 potential targets were obtained from 9 high-frequency CMH. GSE44426 and GSE124281 data sets screened out 24 gene samples, including 14 of the healthy control group and 10 of the PMF group, and identified 319 DEGs between the two groups, including 122 up-regulated genes and 197 down-regulated genes. WGCNA screened out 24 co-expression module genes and found that the five modules closely related to the onset of PMF were MEpink, MEdarkred, MEblack, MEgrey, and MEturquoise, involving 7112 key module hub genes. The GO and KEGG enrichment analyses indicated that lipids and the atherosclerosis pathways were mainly involved in the mechanism of above high-frequency CMH in treating PMF, which included six hub protein targets: HSP90AA1, HSP90AB1, SRC, MAPK1, IL1B and IL10. From the drug-ingredient-target network, seven active ingredients of CMH targeting at these six hub targets were found, including verbascoside, verbascos isoflavone, kaempferol, luteolin, naringenin, quercetin and pachymic acid. The molecular docking and molecular dynamics analyses showed that the key CMH were Shudihuang, Huangqi, Baishao, Danshen, Gancao and Fuling, and among the seven active ingredients, calycosin had the highest binding affinity with HSP90AB1. ConclusionThe main CMH for the treatment of PMF may be Shudihuang, Huangqi, Baishao, Danshen, Gancao and Fuling, and the active ingredients include verbascoside, verbascos isoflavones, kaempferol, luteolin, naringenin, quercetin and pachymic acid. The relevant targets are HSP90AA1, HSP90AB1, SRC, MAPK1, IL-10, and IL-1β, and the most critical pathways are lipid and atherosclerosis pathways.
2.Venetoclax combined with dose-reduced HAD as induction treatment for patients with de-novo acute myeloid leukemia
Zhangsong YAN ; Yang LI ; Bin ZHANG ; Jinsong HE ; Jiesi LI ; Shuning WEI ; Qi WANG ; Qiuling LI ; Kaiqi LIU ; Yingchang MI
Chinese Journal of Hematology 2024;45(4):387-390
The efficacy and safety of venetoclax combined with reduced dose HAD regimen in the treatment of newly diagnosed acute myeloid leukemia (AML) was investigated. From May 2022 to January 2023, a total of 25 patients with newly diagnosed AML were treated with venetoclax combined with reduced-dose HAD regimen as induction therapy. Accoding to the 2017 ELN recommendations, 13 (52.0%) in favoable, 3 (12.0%) in intemediate, and 9 (36.0%) in adverse. The ORR (CR rate+PR rate) was 88.0%, and the CR rate was 84.0%. By May 30, 2023, with a median follow-up of 9 months, 1 year overall survival, event-free survival, and relapse-free survival were 100%, 94.7%, and 94.7%, respectively. All patients received 1-5 cycles of consolidation therapy and two median cycles. Treatment with venetoclax and reduced dose of HAD regimen in the treatment of patients with newly diagnosed AML was high effective and safe.
3.A case of hypopharyngeal amyloidosis by digestive endoscopy
Ling HE ; Wei SU ; Lingli LI ; Qiao ZHOU ; Qiuling ZHAO ; Hongping LI
Journal of Central South University(Medical Sciences) 2024;49(4):643-648
Amyloidosis is a rare disease.This paper reports a case of localized secondary hypopharyngeal amyloidosis presenting with pulmonary tuberculosis as the initial symptom.The patient lacked specific clinical manifestations and primarily exhibited symptoms such as cough,sputum production,acid reflux,belching,and abdominal pain.Chest CT indicated bronchiectasis with infection and pulmonary tuberculosis.Digestive endoscopy revealed a white mucosal elevation at the right pyriform sinus of the hypopharynx.Pathological diagnosis confirmed amyloid deposits in the hypopharyngeal mucosal tissue.The patient tested positive for anti-amyloid A antibodies,Congo red staining(+),and periodate Schiff staining(+).Amyloidosis commonly affects the digestive system and may have various etiologies,often presenting with symptoms that overlap with other digestive system diseases,leading to frequent misdiagnosis and missed optimal treatment opportunities.The hypopharynx,a highly folded and narrow chamber that serves as a common passage for the digestive and respiratory tracts,can be effectively evaluated for amyloidosis using digestive endoscopy.
4.Risk factors for postoperative complications Clavien-Dindo classification≥gradeⅡ after lung cancer surgery
Xiaoqing LIAO ; Zhang CHEN ; Wei DAI ; Xing WEI ; Yang3 PU ; Chao LIN ; Wenhong FENG ; Yuanqiang ZHANG ; Yunfei MU ; Rui ZHANG ; Shaohua XIE ; Xin WANG ; Qiuling SHI ; Qiang LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(08):1151-1157
Objective To investigate the risk factors for postoperative complications Clavien-Dindo classification≥grade Ⅱ after lung cancer surgery. Methods The patients who underwent lung cancer surgery in a multicenter observational study from November 2017 to January 2020 were included. The Clavien-Dindo classification of postoperative complications was analyzed. Logistic regression was used to identify the risk factors for complications≥ gradeⅡ. Results A total of 388 patients were enrolled, including 203 males and 185 females with a mean age of 56.14±10.36 years. The incidence of postoperative complications was 25.52% (99/388) after lung cancer surgery and the incidence of complications≥gradeⅡ was 20.10% (78/388). The five most common postoperative complications were pneumonia (6.96%), prolonged pulmonary air leak (>7 days, 5.67%), incision dehiscence (4.64%), arrhythmia (3.87%), and postoperative pleural effusion (3.35%). Multivariate analysis showed that open surgery [reference: uniportal thoracoscopic surgery, OR=2.18, 95%CI (1.01, 4.70), P=0.047], extended resection [reference: sublobar resection, OR=2.86, 95%CI (1.11, 7.19), P=0.030; reference: lobectomy, OR=2.20, 95%CI (1.10, 4.40), P=0.026] and operative time≥3 h [OR=2.07, 95%CI (1.12, 3.85), P=0.021] were independent risk factors for postoperative complications≥gradeⅡ after lung cancer surgery. Conclusion Surgical approach, extent of resection and operative time are independent influencing factors for postoperative complications≥gradeⅡ after lung cancer surgery.
5.Method exploration of telephone follow-up in clinical research
Xing WEI ; Qi ZHANG ; Xin GAO ; Wenwu LIU ; Yangjun LIU ; Wei DAI ; Peihong HU ; Yaqin WANG ; Jia LIAO ; Hongfan YU ; Ruoyan GONG ; Ding YANG ; Wei XU ; Yang PU ; Qingsong YU ; Yuanyuan YANG ; Qiuling SHI ; Qiang LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(09):1235-1239
Telephone follow-up is one of the important ways to follow up patients. High-quality follow-up can benefit both doctors and patients. However, clinical research-related follow-up is often faced with problems such as time-consuming, laborious and poor patient compliance. The authors belong to a team that has been committed to the study of patient-reported outcomes for a long time. The team has carried out long-term follow-up of symptoms, daily function and postoperative complications of more than 1 000 patients after lung cancer surgery, and accumulated certain experience. In this paper, the experience of telephone follow-up was summarized and discussed with relevant literatures from the aspects of clarifying the purpose of clinical research follow-up, understanding the needs of patients in follow-up, and using follow-up skills.
6.Analysis of constipation status and influencing factors in patients with lung cancer during postoperative hospitalization
Heling ZHOU ; Yanhua JIANG ; Chuanmei WU ; Yanli CHEN ; Qiuyue TANG ; Shan LUO ; Yaqin WANG ; Jia LIAO ; Xing WEI ; Zhen DAI ; Wei DAI ; Qiuling SHI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(10):1402-1406
Objective To investigate the current status of constipation during postoperative hospitalization and the factors associated with moderate to severe constipation at discharge in lung cancer patients. Methods Lung cancer patients who underwent surgery in 6 tertiary hospitals in Sichuan Province from November 2017 to January 2020 were enrolled. The MD Anderson Symptom Scale-Lung Cancer Module was used to collect postoperative constipation scores. Unconditional logistic stepwise regression was used to analyze the related influencing factors for moderate to severe constipation on the day of discharge. Results Finally 337 patients were collected. There were 171 males and 166 females, with an average age of 55.0±10.3 years. Constipation scores of lung cancer patients increased from postoperative day 1 to day 3, and showed a decreasing trend from day 3 to day 7. Moderate to severe constipation was present in 68 (20.2%) patients at discharge. The postoperative hospital stay (OR=0.743, P<0.001) and the dose of morphine used during postoperative hospitalization (OR=1.002, P=0.015) were influencing factors for moderate to severe constipation at discharge in lung cancer patients. Conclusion Lung cancer patients have the most severe constipation on postoperative day 3. Moderate to severe constipation at discharge is associated with the postoperative hospital stay and the dose of morphine used during postoperative hospitalization.
7.Consistency analysis of perioperative self-reported pain scores and clinical records in patients with lung cancer
Yaqin WANG ; Hongfan YU ; Wei DAI ; Xing WEI ; Jia LIAO ; Xiaoqun HU ; Ruoyan GONG ; Qiuling SHI ; Xiaoqin LIU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(11):1545-1550
Objective To analyse the consistency of perioperative self-reported pain scores of lung cancer patients with clinical records to provide a basis for optimal pain management. Methods The patients with lung cancer who underwent surgical treatment in the Department of Thoracic Surgery, Sichuan Cancer Hospital from November 2017 to January 2020 were selected. They were divided into two groups based on the source of pain data. The self-report group used a questionnaire in which patients self-reported their pain scores, and the pain scores for the clinical record group were extracted from the electronic medical record system. Kappa test was used to compare the concordance of pain scores between the two groups preoperatively, on postoperative 1-6 days and on the day of discharge. McNemar's paired χ2 test was used to compare the differences in pain intensity levels between the two groups. Binary logistic multi-factor regression was used to analyse the factors influencing the concordance of severe pain (7-10 points) between the two groups. Results Totally 354 patients were collected, including 191 males and 163 females, with an average age of 55.64± 10.34 years. The median postoperative hospital stay was 6 days. The consistency of pain scores between the two groups was poor (Kappa=–0.035 to 0.262, P<0.05), and the distribution of pain levels at each time point was inconsistent and statistically significant (P<0.001). The percentage of inconsistent severe pain assessment ranged from 0.28% to 35.56%, with the highest percentage of inconsistent severe pain assessment on postoperative day 1 (35.56%). Single-port thoracoscopic surgical access was an influencing factor for inconsistent assessment of severe pain on postoperative day 3 (OR=2.571, P=0.005). Conclusion Self-reported perioperative pain scores of lung cancer patients are poorly aligned with clinical records. Clinical measures are needed to improve the accuracy of patient pain data reporting by choosing the correct assessment method, increasing education, and developing effective quality control measures.
8.Comparison of Quality of Life of the Patients Three Months after Uniportal and Multiportal Thoracoscopic Lobectomy.
Qi ZHANG ; Wei DAI ; Xing WEI ; Run XIANG ; Hang GU ; Peihong HU ; Mingxin LIU ; Wei CHEN ; Huaijun GONG ; Yong LIANG ; Shichao ZHANG ; Weixing PENG ; Qiuling SHI ; Qiang LI ; Nanbin YU
Chinese Journal of Lung Cancer 2023;26(11):843-850
BACKGROUND:
The relationship between quality of life at three months after lung cancer surgery and different surgical approaches is remains unclear. This study aimed to compare the quality of life of patients three months after uniportal and multiportal thoracoscopic lobectomy.
METHODS:
Data from patients who underwent lung surgery at the Department of Thoracic Surgery, Sichuan Cancer Hospital between April 2021 and October 2021 were collected. The European Organization for Research and Treatment of Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29) were used to collect quality of life data of the patients. Potential confounding factors in the baseline data were included in a multivariate regression model for adjustment, and the quality of life of the two groups three months postoperatively was compared with traditional clinical outcomes.
RESULTS:
A total of 130 lung cancer patients were included, with 57 males (43.8%) and 73 females (56.2%), and an average age of (57.1±9.5) yr. In the baseline data of the two groups, there was a statistical difference in the number of chest drainage tubes placed (P<0.001). After adjustment with the regression model, at three months postoperatively, there were no significant differences in all symptoms and functional status scores between the two groups (all P>0.05). The multiportal group had longer surgery time (120.0 min vs 85.0 min, P=0.001), postoperative hospital stay (6.0 d vs 4.0 d, P=0.020), and a higher incidence of early ≥ grade 2 complications (39.0% vs 10.1%, P=0.011) compared to the uniportal group.
CONCLUSIONS
Patients undergoing uniportal and multiportal thoracoscopic lobectomy have similar quality of life at three months postoperatively. The uniportal group may have certain advantages in terms of traditional clinical outcome indicators such as operation time, postoperative hospital stay, and early postoperative complications.
Male
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Female
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Humans
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Lung Neoplasms/surgery*
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Quality of Life
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Thoracic Surgery, Video-Assisted/adverse effects*
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Pneumonectomy/adverse effects*
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Postoperative Complications/surgery*
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Retrospective Studies
9.Discussion of the process of conducting an investigator-initiated research
Wei DAI ; Xing WEI ; Yaqin WANG ; Yangjun LIU ; Jia LIAO ; Shaohua XIE ; Bin HU ; Hongfan YU ; Yang PU ; Wei XU ; Yuqian ZHAO ; Fang LIU ; Xiaoqin LIU ; Xiang ZHUANG ; Biyu SHEN ; Shaoping WAN ; Qiang LI ; Qiuling SHI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(02):299-304
The number of investigator initiated research (IIR) is increasing. But the recognition and management of IIR in China is still in its infancy, and there is a lack of specific and operable guidance for the implementation process. Based on our practical experiences, previous literature reports, and current policy regulations, the authors took prospective IIR as an example to summarize the implementation process of IIR into 14 steps, which are as the following: study initiation, ethical review, study registration, study filing, case report form design, database establishment, standard operating procedure making, investigator training, informed consent, data collection, data entry, data verification, data locking and data archiving.
10.Efficacy and safety of anti-B cell maturation antigen chimeric antigen receptor T-cell for retreatment of relapsed/refractory multiple myeloma
Guoxing ZHAO ; Zhi CHENG ; Runhong WEI ; Yi WU ; Lei FENG ; Qiuling MA ; Xianhui LIU
Journal of Leukemia & Lymphoma 2022;31(4):229-234
Objective:To explore the efficacy and safety of anti-B cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) for the retreatment of relapsed and refractory multiple myeloma (RRMM).Methods:The clinical data of 10 RRMM patients who received anti-BCMA CAR-T therapy for the second time (CART2) in Henan Province Hospital of Traditional Chinese Medicine due to failure or recurrence after their first anti-BCMA CAR-T (CART1) therapy from January 2017 to June 2021 were retrospectively analyzed. The treatment, efficacy and adverse events of patients receiving CART2 therapy were summarized; and the objective response rate (ORR), median duration of response (DOR) and incidence of adverse reactions were compared between CART1 and CART2.Results:Among 10 patients, 8 were males and 2 were females, with a median age of 57 years (41-70 years). Patients' 3-month ORR after CART1 therapy was 90%, and the median DOR was 16.0 months (3.0-27.0 months). CART2 used human-derived anti-BCMA CAR-T to treat 6 cases and mouse-derived anti-BCMA CAR-T to treat 4 cases. The 3-month ORR of patients receiving CART2 therapy was 40%, and the median DOR was 8.5 months (3.0-11.0 months). Among 9 patients who received mouse-derived anti-BCMA CAR-T in CART1 therapy, 4 of them received the same product again and none of them showed curative effect. Among 6 patients retreated with human-derived anti-BCMA CAR-T, 4 patients (66.7%) of them achieved partial remission (PR) or better. During CART1 therapy, 10 patients developed grade 1-2 cytokine release syndrome (CRS), and 7 patients developed different degrees of decrease in leukocyte, neutrophil absolute count (ANC) and platelet. Among patients who achieved effective outcomes after receiving CART2 therapy, 4 patients of them developed grade 1-2 CRS, and different degrees of decrease in white blood cell, ANC and thrombocytopenia. Immune effector cell-related neurotoxicity syndrome was not observed.Conclusions:Anti-BCMA CAR-T is effective and safe to retreat RRMM. The ORR and DOR of patients receiving CART2 therapy are lower than those of patients receiving CART1 therapy. CRS and cytopenia are common adverse reactions.

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