1.LIU Shenlin's Experience in Treating Gastric Cancer with the Thinking of "Prescription According to Tendency"
Qingmin SUN ; Cancan ZHANG ; Xiaoxia ZHENG ; Yujia LU ; Xiang ZHANG ; Shanshan ZHENG ; Jian WU ;
Journal of Traditional Chinese Medicine 2024;65(20):2075-2080
This paper summarized the clinical experience of Professor LIU Shenlin in diagnosing and treating gastric cancer with the thinking of "prescription according to tendency". In this paper, the thinking of diagnosis and treatment for gastric cancer and medication skills were summarized into four dimensions: power, energy, chronology and situation. The diagnosis emphasizes the tendency of qi power, considering that the onset of gastric cancer primarily stems from the disorder of qi movement in zang-fu organs, and emphasizing the importance of regulating the liver and spleen qi to intercept the tendency of disease. It points out that dampness-phlegm-stasis-toxin is a crucial link leading to the metabolic imbalance of body energy, and Professor LIU adepts at using methods such as breaking up blood and expelling stasis, and clearing heat and resolving toxins to block the pathological chain reaction caused by energy imbalance and to restore the homeostasis of the organism. In the treatment process, according to the characteristics of gastric cancer staging and chronological evolution, we will explore the changes of the exuberance and weakness of healthy qi and pathogenic qi in the context of the chronologic tendency, and adjust the dosage of attacking and tonic medicines in different stages of the disease in order to balance and restore the body. The "situation" is in line with the state of consumptive disease in advanced gastric cancer, Professor LIU skillfully uses large doses of Huangqi (Astragalus mongholicus) with flexible combination of medicinals to replenish deficiencies, invigorate qi, and regulate blood vessels.
2.Causal relationship between educational attainment and pancreatitis: a Mendelian randomization study
Ruiqi CAO ; Zhengyuan FENG ; Jiaoxing WU ; Jie LI ; Zheng WANG ; Zheng WU ; Cancan ZHOU
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(2):200-205
【Objective】 To explore the causal relationship between education level and pancreatitis risk through Mendelian randomization. 【Methods】 A two-sample Mendelian randomization analysis was conducted using genome-wide association study (GWAS) summary data. The GWAS data for education level and pancreatitis were obtained from SSGAC database and the FinnGen database (version R9). Causal relationship between education level and pancreatitis was explored using the inverse variance weighted (IVW), MR-Egger, and weighted median methods. Heterogeneity and directional pleiotropy were evaluated using Cochran’s Q test and funnel plots. 【Results】 Totally 604 SNPs associated with education level were included. The results provided evidence that there was negative relationship between education level and pancreatitis risk. For acute pancreatitis, OR=0.52, 95% CI: 0.44-0.62, P=2.43×10-14 while for chronic pancreatitis, OR=0.51, 95% CI: 0.41-0.64, P=7.20×10-9. Results from MR-Egger and weighted median analyses obtained the same results. The results of sensitivity analysis indicated that this study did not violate the basic assumptions of Mendelian randomization. 【Conclusion】 There is a causal relationship between education level and the occurrence of pancreatitis. The educational level is negatively correlated with the risk of pancreatitis.
3.Progress of magnetic iron oxide nanoparticles in targeted diagnosis and treatment of pancreatic cancer
Jiaqiang REN ; Shuai WU ; Jiantao MO ; Cancan ZHOU ; Liang HAN ; Zheng WU
Journal of Surgery Concepts & Practice 2024;29(1):61-66
Pancreatic cancer has a very poor prognosis.Early diagnosis and treatment are especially critical for improving its prognosis.Nanotechnology has been widely used in the diagnosis and treatment of pancreatic cancer.Relying on the unique physicochemical properties of nanoparticles and their rich surface modifications,effective enrichment of tumor sites can be achieved.Magnetic iron oxide nanoparticles(MIONPs)is one of the commonly used nanomaterials in the diagnosis and treatment of pancreatic cancer,and has good biocompatibility.Through special surface modification,it can be used in targeted diagnosis and treatment of pancreatic cancer.MIONPs can be used as a contrast agent for MRI,and by modifying the surface,they also can be used in targeted imaging of pancreatic cancer.And they can also be modified as a drug delivery system to achieve targeted delivery of drugs and improve therapeutic effects.However,the application of MIONPs in pancreatic cancer diagnosis and treatment still faces some challenges,such as nanotoxicity and cost issues.With the development of technology,MIONPs are expected to play an important role in the personalized diagnosis and treatment of pancreatic cancer.
4.KCTD4 interacts with CLIC1 to disrupt calcium homeostasis and promote metastasis in esophageal cancer.
Cancan ZHENG ; Xiaomei YU ; Taoyang XU ; Zhichao LIU ; Zhili JIANG ; Jiaojiao XU ; Jing YANG ; Guogeng ZHANG ; Yan HE ; Han YANG ; Xingyuan SHI ; Zhigang LI ; Jinbao LIU ; Wen Wen XU
Acta Pharmaceutica Sinica B 2023;13(10):4217-4233
Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca2+ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca2+-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.
5.Clinical characteristics analysis of acute pancreatitis
Qiqi WANG ; Yali CHENG ; Cancan ZHOU ; Mengyuan GONG ; Haonan LIU ; Zheng WANG ; Qingyong MA ; Zheng WU
Chinese Journal of Digestive Surgery 2023;22(S1):38-43
Objective:To analyze the clinical characteristics of acute pancreatitis.Methods:The retrospective case-control study was conducted. The clinical data of 558 patients with acute pancreatitis who were admitted to The First Affiliated Hospital of Xi′an Jiaotong University from June 2015 to June 2023 were collected. There were 352 males and 206 females, aged (46±15)years. Observation indicators: (1) general situations of acute pancreatitis patients; (2) etiology of acute pancreatitis patients; (3) severity of acute pancreatitis patients; (4) chronic diseases in acute pan-creatitis patients; (5) complications in acute pancreatitis patients; (6) subgroup analysis of patients with recurrent acute pancreatitis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Bonferroni correction was used for pairwise comparison. Results:(1) General situations of acute pancreatitis patients. There were significant differences in gender, age, total duration of hospital stay, smoking, and alcohol consumption between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (2) Etiology of acute pancreatitis patients. There were significant differences in gallstones and hyperlipidemia between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (3) Severity of acute pancreatitis patients. Of the 443 patients with first episode of acute pancreatitis and 115 patients with recurrent acute pancreatitis, cases with mild acute pancreatitis, cases with moderate-severe acute pancreatitis, cases with severe acute pan-creatitis were 320 and 83, 24 and 9, 99 and 23, showing no significant difference between them ( P>0.05). (4) Chronic diseases in acute pancreatitis patients. There were significant differences in com-plication as hyperlipidemia, fatty liver and diabetes between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (5) Complications in acute pancrea-titis patients. There was no significant difference in terms of acute necrotic collection, acute peripan-creatic fluid accumulation, walled-off necrosis, pancreatic pseudocyst, infectious pancreatic necrosis, systemic inflammatory response syndrome, respiratory system complications, circulatory system complications, renal complications, sepsis, abdominal compartment syndrome, or pancreatic ence-phalopathy between the first episode of acute pancreatitis patients and the recurrent acute pancrea-titis patients ( P>0.05). (6) Subgroup analysis of patients with recurrent acute pancreatitis. ① Combination with chronic diseases. Of the 115 patients with recurrent acute pancreatitis, cases with mild acute pancreatitis, cases with moderate-severe acute pancreatitis, cases with severe acute pancreatitis were 83, 9, 23, and there were 25, 8, 11 cases of them with hyperlipidemia, respectively, showing a significant difference among them ( P<0.05). ② Complications. Of the 115 patients with recurrent acute pancreatitis, there were 44 cases with hyperlipidemia and 71 cases without hyper-lipidemia, and there were significant differences in acute peripancreatic fluid accumulation and renal complications between them ( P<0.05). Conclusions:Recurrent acute pancreatitis is more common in males. Compared with first episode of acute pancreatitis, cases with recurrent acute pancreatitis usually have younger age, shorter total duration of hospital stay, higher proportion of smoking and drinking. The etiology of recurrent acute pancreatitis is composed of lower levels of biliary diseases and higher levels of hyperlipidemia. Patients with recurrent acute pancreatitis have higher proportion of comorbidities as hyperlipidemia, fatty liver and diabetes. There was no signifi-cant difference in the incidence of complications between first episode of acute pancreatitis and recurrent acute pancreatitis. Compared with recurrent acute pancreatitis patients without concomi-tant hyperlipidemia, recurrent acute pancreatitis patients with concomitant hyperlipidemia are more prone to acute peripancreatic fluid accumulation and renal complications.
6.Current situation and influencing factors of nurses' willingness to engage in telecare in county-level hospitals in Henan Province
Cancan DU ; Zhixia WANG ; Jiaqi WANG ; Shaoxia WANG ; Xiaoyan ZHENG ; Yajuan WEN ; Tianyun ZHAO ; Lina YANG
Chinese Journal of Modern Nursing 2023;29(36):4981-4986
Objective:To understand the current situation of nurses' willingness to engage in telecare in county-level hospitals in Henan Province and analyze its influencing factors.Methods:Using the convenient sampling method, a total of 1 300 clinical nurses from 6 Class Ⅱ Grade A county-level hospitals in Zhengzhou, Hebi, Zhoukou and other cities in Henan Province were selected as the research objects from August 2022 to January 2023. General Data Questionnaire and Clinical Nurses' Willingness to Engage in Telecare Questionnaire were used to investigate the research objects. Non-parametric test and multiple linear regression were used to analyze the influencing factors of clinical nurses' willingness to engage in telecare.Results:A total of 1 300 questionnaires were sent out in this study, and 1 183 were effectively collected, with an effective recovery rate of 91.00% (1 183/1 300). The total score of Clinical Nurses' Willingness to Engage in Telecare Questionnaire of 1 183 nurses in county-level hospitals was [105.00 (98.00, 112.00) ] points, and all items were scored [3.50 (3.27, 3.73) ]. Multiple linear regression analysis showed that professional title, post, whether they knew about telecare, and the number of times of receiving training on nursing information each year were the influencing factors of nurses' willingness to engage in telecare in county-level hospitals ( P<0.05) . Conclusions:In Henan Province, 1 183 nurses in county-level hospitals have a high willingness to engage in telecare. Relevant departments should further strengthen the publicity of relevant contents of telecare, carry out practical operation training related to nursing information, improve the nursing information ability of nurses in county-level hospitals and strengthen the awareness of health management services, so as to promote the successful implementation of telecare services in rural areas.
7.Association between cardiorespiratory fitness and the risk of cardiovascular and cerebrovascular diseases: a meta-analysis
Yunzhi ZHENG ; Cancan HOU ; Jincheng CAO ; Zongwen CUI ; Mao WANG ; Junpeng CUI
Journal of Preventive Medicine 2022;34(3):282-288
Objective:
To examine the dose-response association between cardiorespiratory fitness ( CRF ) and the risk of cardiovascular and cerebrovascular diseases.
Methods:
A joint search was performed in Chinese and English electronic databases, including China National Knowledge Infrastructure ( CNKI ) , Wanfang Data, VIP, CBM, PubMed, Embase and Web of Science, to retrieve publications reporting the correlation between CRF and the risk of cardiovascular and cerebrovascular diseases until May, 2021. The pooled risk was estimated using the random effects model, and the dose-response association was evaluated using restricted cubic splines. The source of heterogeneity was assessed by subgroup analysis, and the stability of the results was tested by the trim-and-fill method, while the publication bias was assessed using funnel plots.
Results:
Totally 37 280 literatures were identified, and 23 eligible studies were finally included in the analysis, which covered 2 605 622 subjects. There were 22 publications identified as high-quality. Meta-analysis revealed that the pooled risk of cardiovascular and cerebrovascular diseases reduced by 42% in the highest CRF group relative to the lowest CRF group ( OR=0.58, 95%CI: 0.52-0.65 ), and a one metabolic equivalent ( MET ) increase in CRF caused a 10% reduction in the pooled risk of cardiovascular and cerebrovascular diseases ( OR=0.90, 95%CI: 0.88-0.92 ). There was a negative linear correlation between CRF and the incidence of cardiovascular and cerebrovascular diseases ( P=0.396 ). Subgroup analysis identified gender, sample size and study regions as possible sources of heterogeneity, and sensitivity analysis showed that the study results were stable.
Conclusions
There is a negative linear correlation between CRF and the risk of cardiovascular and cerebrovascular diseases, and an increase in CRF may reduce the risk of cardiovascular and cerebrovascular diseases.
8.One-step multiplex nested real-time RT-PCR assay for 2019-nCoV and Influenza A/B viruses detection
Kui ZHENG ; Fangfang SUN ; Cancan YAO ; Jun DAI ; Yongxia SHI ; Xiaobo LI ; Jicheng HUANG
Chinese Journal of Laboratory Medicine 2022;45(11):1144-1149
Objective:To develop a single-tube one-step multiplex nested real-time reverse transcription polymerase chain reaction (RT-PCR) assay for the simultaneous detection of 2019-nCoV, influenza A virus, influenza B virus and internal-control with human-derived gene.Methods:This study included 30 positive specimens for 2019-nCoV nucleic acid detection and 336 screening specimens collected from the arrivals at Guangzhou Baiyun Airport between February 2020 and February 2022. Sixty-four positive specimens of other respiratory pathogens were also collected from the arrivals at Guangzhou Baiyun Airport during the three-year period before the occurrence of COVID19 outbreak in 2020, and 7 positive viral strains of respiratory pathogens were provided by collaborative laboratories. In order to establish a set of multiplex nested real-time RT-PCR assay, a group of primers and probe combinations for a multiplex nested real-time RT-PCR was designed and screened according to a selection of nucleotide conserved regions of the ORF and N genes of 2019-nCoV and the M gene of influenza A and B viruses, while nested amplification primers and probe for the internal-control with human-derived gene were introduced. Then the prepared pseudovirus-positive quality control and sample discs were applied to evaluate the sensitivity and specificity. Clinical specimens were performed to validate the applicability of the method.Results:The results show that the established one-step multiplex nested real-time RT-PCR assay can specifically detect 2019-nCoV and influenza A and B viruses, with the limit-of-detection of about 125 copies/ml for 2019-nCoV and about 250 copies/ml for influenza A and B viruses. Totally 101 positive samples of various respiratory pathogens were detected, showing that the detection sensitivities of 2019-nCoV and influenza A and B viruses were 96.67%, 92.86% and 96.15%, respectively, with the specificity of 100%. No false-positive detection was found in the applied detection of more than 300 clinical samples.Conclusions:A one-step multiplex nested real-time RT-PCR assay for 2019-nCoV, influenza A and B viruses and human-derived gene internal-control was developed. The assay has good sensitivity and specificity and can be used for rapid screening of 2019-nCoV and influenza A and B viruses in high-volume samples.
9.Effects of subchronic exposure to benzoɑpyrene on memory function and mRNA expressions of NMDA receptors in different brain regions in rats
Zhaofei LI ; Shanshan CHANG ; Cancan GUO ; Yi LYU ; Jinping ZHENG
Journal of Environmental and Occupational Medicine 2022;39(7):804-808
Background The altered expressions of hippocampal N-methyl-D-aspartate (NMDA) receptors induced by benzo[ɑ]pyrene (BaP) causes short-term spatial learning and memory impairment in humans and animals, but whether BaP causes alterations of NMDA receptor subunits in other brain regions and the associated neurotoxic mechanism is still essentially unknown. Objective To observe the mRNA expressions of NR1, NR2A, and NR2B of NMDA receptor subunits in different brain regions in SD rat model with subchronic exposure to BaP, and to provide a basis for in-depth study of the mechanism of BaP-induced neurotoxicity. Methods Forty male SD rats were selected and randomly divided into a control group and 1.00, 2.50, and 6.25 mg·kg−1 BaP exposure groups with 10 rats in each group. The exposure rats received intraperitoneal injection of BaP every other day for 90 d.The average latency to platform, the average total distance, and the duration spent in previous quadrant were measured by the Morris Water Maze. Real-time fluorescence quantitative PCR was used to detect the mRNA expressions of NR1, NR2A, and NR2B in hippocampus, cortex, cerebellum, and striatum of rats. Results The average latency to platform and the average total distance in the 2.50 and 6.25 mg·kg−1 BaP groups were significantly prolonged compared with the control group (P<0.05), and the duration that rats spent in previous quadrant in the 6.25 mg·kg−1 BaP group was significantly shortened (P<0.05). Compared with the control group, the mRNA expressions of NR1 and NR2B in the hippocampus in the 2.50 and 6.25 mg·kg−1 BaP groups were significantly reduced (P<0.05), and the NR2A mRNA expression in the hippocampus in the 6.25 mg·kg−1 BaP group was significantly reduced (P<0.05); the mRNA expressions of NR1 and NR2B in the cortical tissue in the 6.25 mg·kg−1 BaP group were significantly reduced (P<0.05), and the mRNA expression of NR2A in the cortical tissue in the 1.00 mg·kg−1 BaP group was reduced; the mRNA expression of NR2B in the cerebellar tissue in the 6.25 mg·kg−1 BaP group was significantly reduced (P<0.05); there were no differences in the mRNA expressions of NMDA receptor subunits in the striatum tissue (P>0.05). Conclusion Subchronic BaP exposure can cause short-term spatial learning and memory impairment in rats, which may be related to the down-regulation of mRNA expressions of NR1, NR2A, and NR2B in hippocampus, changes of mRNA expressions of NR1, NR2A, and NR2B in cortical area, and the down-regulation of NR2B mRNA expression in cerebellum.
10.Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner.
Cancan ZHENG ; Xiaomei YU ; Yiyao LIANG ; Yidong ZHU ; Yan HE ; Long LIAO ; Dingkang WANG ; Yanming YANG ; Xingfeng YIN ; Ang LI ; Qingyu HE ; Bin LI
Acta Pharmaceutica Sinica B 2022;12(3):1271-1287
As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease.


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