1.RP11-789C1.1 inhibits gastric cancer cell proliferation and accelerates apoptosis via the ATR/CHK1 signaling pathway
Wenwei LIU ; Wei FENG ; Yongxin ZHANG ; Tianxiang LEI ; Xiaofeng WANG ; Tang QIAO ; Zehong CHEN ; Wu SONG
Chinese Medical Journal 2024;137(15):1835-1843
Background::Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully understood.Methods::We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells. In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin. Results::Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxiatelangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin sensitivity.Conclusion::In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.
2.Predictive value of effective hepatic blood flow in postopera-tive liver insufficiency in patients with hepatocellular carci-noma
Sen CHEN ; Yan-Guo LIU ; Yong-Ming ZHANG ; Song-Zhu YANG
Chinese Journal of Current Advances in General Surgery 2024;27(5):373-376
Objective:To investigate the value of effective hepatic blood flow in predicting the occurrence of liver insufficiency after operation of hepatocellular carcinoma(HCC).Methods:The 15-minute clearance of Indocyanine Green(ICGR15)and EHBFwere measured in 123 patients with hepatocellular carcinoma(HCC)after hepatectomy.To compare the difference of ICGR15 and EHBF in different groups of liver function recovery and the incidence of postoperative liver function insufficiency in different groups of ICG R15 and EHBF.The diagnostic value of ICG R15 and EHBF was compared by receiver operating characteristic(ROC)curve.Results:Of the 123 patients,41(33.3%)developed liver insufficiency after operation.The average values of ICG R15 and EHBF in patients with good liver function were(8.95±7.18)%and(1.01±0.37)min,respectively,while those in patients with liver insufficiency were(15.88±11.55)%and(0.75±0.28)min,respec-tively.The difference was statistically significant(P<0.05).The incidence of postoperative liver in-sufficiency was 13.0%in EHBF≥1.0 L/min group and 45.5%in<1.0 L/min group,the difference was statistically significant(P<0.05).The area under the ICG R15 ROC curve was 0.710(95%CI:0.616-0.804),the critical value was 7.6,the sensitivity was 78.0%,and the specificity was 59.8%.The area under the EHBF ROC curve was 0.718(95%CI:0.624-0.813),the critical value was 0.35,the sensitivity was 73.2%,and the specificity was 70.7%.Conclusion:EHBF can effec-tively predict the occurrence of liver insufficiency after hepatocellular carcinoma operation,and may have the same testing efficacy as ICGR15.
3.Effect of Precocious Puberty on Glucose and Lipid Metabolism in Female Rats
Xiaoya LIN ; Baojiang HUANG ; Jun ZHANG ; Song GUO ; Huamei MA ; Yanhong LI ; Minlian DU ; Qiuli CHEN
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(2):233-242
ObjectiveTo explore the effect of precocious puberty on glucose metabolism and lipid metabolism in female rats. MethodsSixty two-day-old female rats were randomly divided into 2 groups. When aged 5 days, the precocious puberty group and normal group were given a single subcutaneous injection of danazol and solvent soybean oil respectively. The vaginal opening of rats was monitored from their 21 days of age. After 12 hours of fasting, all successful modeling rats were randomly executed within 3 days after vaginal opening, when aged 7 and 12 weeks. Then we measured the rats’ body weight and length, determined the concentrations of glucose, insulin, blood lipids, estradiol, leptin and adiponectin with enzyme-linked immunosorbent assay and observed the pathological changes of perirenal fat, uterus and ovary. ResultsFor body weight and length, rats in the precocious puberty group were smaller than those in the normal group within 3 days after vaginal opening, but which did not affect their subsequent growth and development, and there was no significant difference between the two groups at 7 and 12 weeks of age. Within 3 days after vaginal opening, insulin levels had significant difference between the two groups (P = 0.001), the precocious group showed hyperinsulinemia and increased number of perirenal adipocytes. At three execution times, no significant difference was noted in estradiol, leptin and adiponectin levels between the two groups. The same was true in the ratios of ovary or uterus to body weight between the two groups. ConclusionsPrecocious puberty makes earlier onset of pubertal development and allows body maladaptation to the sudden changes of the internal environment. However, the changes due to precocious puberty are temporary and reversible, and they may become normal in adulthood.
4.Correlation analysis between tumor burden and biochemical indicators of parathyroid adenoma
Qingyuan ZHENG ; An SONG ; Tianqi CHEN ; Sen YANG ; Jinheng XIAO ; Ya HU ; Quan LIAO
Chinese Journal of Endocrine Surgery 2024;18(1):35-39
Objective:To determine the correlation of tumor volume and weight with biochemical parameters in patients with parathyroid adenoma (PA) .Methods:A prospective electronic database collected clinical data on 208 patients with PA treated for the first time by surgery at department of general surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.The relationship between biochemical parameters and tumor volume and weight was analyzed with Spearman’s correlation.Results:Tumor volume and weight were positively correlated with parathyroid hormone (PTH) ( r=0.33, P<0.001; r=0.39, P<0.001), calcium ( r=0.16, P=0.018; r=0.18, P=0.007) and alkaline phosphatase levels ( r=0.24, P<0.001; r=0.27, P<0.001), respectively. Clinical correlates affecting serum PTH were age, serum calcium and tumor weight ( F=30.325, P<0.001) . Conclusions:Tumor burden in patients with PA correlates with some laboratory biochemical parameters. Age and cystic lesions of the tumor may influence the actual serum PTH levels.
5.Comparison of Anatomic Locking Titanium Plate and Intramedullary Nail in the Treatment of Distal Tibial Fractures
Mengjun MA ; Yanbo CHEN ; Gang ZENG ; Chen CHEN ; Weidong SONG ; Wenzhou LIU
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(1):108-113
ObjectivesTo compare the clinical efficacy and complications of anatomic locking titanium plate (hereinafter referred to as “titanium plate screw”) and intramedullary nail in the treatment of distal tibial fractures.Methods From September 2019 to September 2021, 32 patients diagnosed with AO-A fracture of distal tibia at Sun Yat-sen Memorial Hospital of Sun Yat-sen University were included in this study. Of these, 15 cases were treated with titanium plate screws and 17 cases were treated with intramedullary nails. General surgical indexes, fracture healing time and postoperative operation were compared between the two groups.ResultsAll patients were followed up for 10 to 20 months, with an average of 12 months. The operative time and intraoperative fluoroscopy times of intramedullary nail group were longer than those of titanium plate screw group, but the preoperative waiting time and hospitalization days was less or were fewer than those of titanium plate screw group, the difference was statistically significant (P < 0.05). There was no significant difference in fracture healing time between the two groups (P> 0.05). At 6 weeks after operation, VAS scores in both groups were lower than those before operation, with statistically significant difference (P<0.05). There was no significant difference in VAS scores between the intramedullary nail group and the titanium plate screw group (P> 0.05). AOFAS scores 6 months after surgery, ankle joint motion and complication rate 1 year after surgery in intramedullary screw group were better than those in titanium plate screw group, and the differences were statistically significant (P< 0.05). There was no significant difference in AOFAS scores between the two groups at 1 year after operation (P> 0.05).ConclusionTitanium plate screw and intramedullary nail are both effective methods for the treatment of distal tibial AO-A fracture, and there is no significant difference in long-term clinical efficacy. Intramedullary nail has fewer soft tissue complications, less impact on ankle motion, faster recovery and higher safety, while titanium plate screw has a higher probability of postoperative soft tissue infection. We suggest that in clinical work, preoperative evaluation of patients should be done well. Under the premise of grasping the indications, intramedullary nail has fewer complications and certain advantages.
6.Protective role and mechanistic exploration of Irisin in doxorubicin induced-cardiomyopathy
Yu-Ge JIN ; Song-Sen LI ; Hao WANG ; Cai-Ru GUO ; Bing-Bing ZHANG ; Hao-Jie CHEN ; Ya-Xin BAN ; Ru-Bing LIANG
The Chinese Journal of Clinical Pharmacology 2024;40(2):220-224
Objective To study the protective effect of Irisin in doxorubicin(Dox)induced-Cardiomyopathy and its possible mechanism.Methods AC 16 cells were used to construct Dox injury model and divided into control group(AC 16 cells were cultured with complete medium),Irisin group(AC16 cells were treated with 10 ng·L-1 Irisin for 24 h),Dox group(AC 16 cells were treated with 4 μmol·L-1 Dox for 24 h),Dox+Irisin group(AC 16 cells were pretreated with 10 ng·L-1 Irisin for 2 h,and then treated with 4 pmol·L-1 Dox for 24 h).Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)and lactate dehydrogenase(LDH)were used to detect the proliferation,apoptosis and mortality of AC 16 cells.Western blot was used to detect the expression levels of nuclear factor-κB(NF-κB)signaling pathway and apoptotic factors B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and caspase-9 protein.Mito-Tracker Red CMXRos probe was used to detect mitochondrial membrane potential.Results In the contrl group,Irisin group,Dox group,Dox+Irisin group,the rate of apoptosis were(0.97±0.09)%,0,(42.80±6.70)%,(11.74±1.79)%;the expression of Bax protein were 0.85±0.01,0.36±0.02,1.15±0.07,0.37±0.11;the expression of caspase-9 protein were 0.52±0.02,0.59±0.03,1.11±0.02,0.67±0.08;the expression of Bcl-2 protein were 1.01±0.04,1.05±0.25,0.43±0.02 and 0.99±0.30;the probability of mitochondrial damage were(0.02±0.01)%,(0.5±0.15)%,(38.6±2.39)%,(1.58±0.54)%.The difference of the above indexes between the contrl group and the Dox group were statistically significant(all P<0.05);the difference between Dox group and Dox+Irisin group were statisically significant(all P<0.05).Conclusion Irisin could reduce the expression level of Bax,caspase-9,p-NF-κB,and p-mTOR caused by Dox,increase the expression level of Bcl-2,ameliorate the myocardial damage caused by Dox,and reduce cardiotoxicity.
8.Preliminary Recommendations on the Timing of Lung Surgery after Novel Coronavirus Infection in Patients with Pulmonary Nodules and Lung Cancer.
Xin LI ; Ming DONG ; Song XU ; Honglin ZHAO ; Sen WEI ; Zuoqing SONG ; Minghui LIU ; Dian REN ; Fan REN ; Qingchun ZHAO ; Renwang LIU ; Chunqiu XIA ; Gang CHEN ; Jun CHEN
Chinese Journal of Lung Cancer 2023;26(2):148-150
In recent years, the corona virus disease 2019 (COVID-19) pandemic has had a huge impact on the global medical, political and economic fields. Since the beginning of the COVID-19 epidemic, our understanding of the impact of COVID-19 has grown exponentially. Recently, the COVID-19 epidemic has changed rapidly in China, and there has been controversy over how to carry out surgical operations for patients with lung neoplastic lesions. Some studies have shown that lung cancer patients undergoing surgery are more likely to experience respiratory failure and perioperative death after contracting COVID-19 than the general population, however, delays in cancer treatment are also associated with increased mortality among these patients. In particular, the novel coronavirus Omikron variant has a higher transmissibility and may escape the immunity obtained through the previous novel coronavirus infection and vaccination. In order to minimize the risk of novel coronavirus infection in surgical patients, it is necessary to develop new treatment guidelines, expert consensus and preventive measures. However, the current rapid change of the epidemic situation has led to insufficient time and evidence to develop guidelines and consensus. Therefore, thoracic surgeons need to evaluate specific patient populations at higher risk of severe complications before surgery and weigh the benefit of surgical treatment against the risk of novel coronavirus infection. We try to give some recommendations on lung surgery during the current domestic epidemic situation based on the guidelines and consensus of oncology and thoracic surgery organizations in different regions on lung surgery.
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Humans
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Lung Neoplasms/complications*
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COVID-19
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SARS-CoV-2
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Multiple Pulmonary Nodules
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Pandemics/prevention & control*
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Lung
9.Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer.
Senlin LI ; Siyu CHEN ; Zhihui DONG ; Xingdong SONG ; Xiuling LI ; Ziqi HUANG ; Huiru LI ; Linzhuo HUANG ; Ganyuan ZHUANG ; Ran LAN ; Mingyan GUO ; Wende LI ; Phei Er SAW ; Lei ZHANG
Acta Pharmaceutica Sinica B 2023;13(3):967-981
Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.
10.Development and Validation of a Predictive Risk Model for Vision-threatening Diabetic Retinopathy in Patients with Type 2 Diabetes
Jin LUO ; Wen-yong HUANG ; Yu-ting LI ; Jian ZHANG ; Min-yu CHEN ; Shu-hui CHEN ; Jia-hui LIU ; Sheng-song HUANG
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(6):999-1007
ObjectiveTo develop and validate a predictive risk model for vision-threatening diabetic retinopathy in patients with type 2 diabetes using readily accessible clinical data, which may provide a convenient and effective prediction tool for early identification and referral of at-risk populations. MethodsA nomogram model was developed using a dataset obtained from patients with T2DM who participated in the Guangzhou Diabetic Eye Study from November 2017 to December 2020. Logistic regression was used to construct the model, and model performance was evaluated using receiver operating characteristic curve, Hosmer-Lemeshow test, calibration curve and decision curve analysis. The model underwent internal validation through the mean AUC of k-fold cross-validation method, and further external validation was conducted in the Dongguan Eye Study. ResultsA total of 2 161 individuals were included in the model development dataset, of whom 135 (6.25%) people were diagnosed with VTDR. Age (P<0.001,OR=0.927,95%CI:0.898~0.957) and body mass index (P<0.001,OR =0.845,95%CI:0.821~0.932) were found to be negatively correlated with VTDR, whereas diabetes duration (P<0.001,OR=1.064,95%CI:1.035~1.094), insulin use (P =0.045,OR =1.534,95%CI:1.010~2.332), systolic blood pressure (P<0.001,OR =1.019,95%CI:1.008~1.029), glycated hemoglobin (P<0.001,OR =1.484,95%CI:1.341~1.643), and serum creatinine (P<0.001,OR =1.017,95%CI:1.010~1.023) were positively correlated with VTDR. All these variables were included in the model as predictors. The model showed strong discrimination in the development dataset with an area under the receiver operating characteristic curve (AUC) of 0.797 and in the external validation dataset (AUC 0.762). The Hosmer-Lemeshow test(P>0.05)and the calibration curve displayed good agreement. Decision curve analysis showed that the nomogram produced net benefit in the two datasets. ConclusionsIndependent factors influencing VTDR include age, duration of diabetes mellitus, insulin use, body mass index, systolic blood pressure, glycosylated hemoglobin, and serum creatinine. The nomogram constructed using these variables demonstrates a high degree of predictive validity. The model can serve as a valuable tool for early detection and referral of VTDR in primary care clinics. Therefore, its application and promotion are highly recommended.

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