Aim To investigate the effect and mechanism of valdecoxib on the apoptosis of human esophageal cancer cells.Methods Flow cytometry was used to observe the effect of valdecoxib on apoptosis and the cell cycle distribution of Eca109 cells.Transmission electron microscope was further used to detect the cell apoptosis.The content of LDH was examined using LDH kit.The expressions of p-p38MAPK,Fas and FasL protein were detected using flow cytometry.Results Valdecoxib of 25～400 ?mol?L~(-1) significantly induced the apoptosis of Eca109 cell line,and the rate of apoptosis was increased from(2.95?0.83)% to(48.46?0.73)%,50～400 ?mol?L~(-1) valdecoxib also decreased the proliferation index and the proportion of cells in the S phase,increased the proportion of cells in the G_0/G_1 phase,but had no effect on the proportion of cells in the G_2/M phase.Compared with those in Eca109 cells cultured in the medium with solvent,the expression of p-p38MAPK,Fas and FasL was higher in the Eca109 cells exposed to valdecoxib in a dose-dependent manner in 72 h.Conclusion Valdecoxib can induce apoptosis of Eca109 cell line partly by up-regulating the expression of p-p38MAPK/Fas/FasL.

Objective: To explore the impact of renal function injury on diagnostic value of NT-proBNP in patients with heart failure (HF).
Methods: A total of 420 patients with cardiovascular disease at (50-75) years of age were divided into 2 groups based on left ventricular ejection fraction (LVEF): Control group, the patients with normal cardiac function, LVEF≥40%,n=232 and HF group, LVEF<40%,n=188. According to estimated glomerular ifltration rate (eGFR), each group contained 4 subgroups by Normal renal function (eGFR≥90 ml/min·1.73m2), Mild renal injury (90>eGFR≥60 ml/min·1.73m2), Moderate renal injury (60>eGFR≥30 ml/min·1.73m2) and Severe renal injury (eGFR<30 ml/min·1.73m2). The changes of NT-proBNP level at different subgroups were observed and the optimal cut-off values of NT-proBNP for HF diagnosis were measured.
Results: Compared with Control group, HF group had increased blood level of NT-proBNP,P<0.05; NT-proBNP level was negatively related to eGFR (in all patients:r=-0.664, in Control group:r=-0.686 and in HF group:r=-0.721,P<0.05). Within Control group, NT-proBNP level was similar between Normal renal function and Mild renal injury subgroups,P>0.05, while it was much higher in Moderate and Severe renal injury subgroups than Normal renal function subgroup,P<0.05. Within HF group, Severe renal injury subgroup had increased NT-proBNP level than other subgroups,P<0.05. The best cut-off value of NT-proBNP for HF diagnosis in patients with normal or mild renal injury was 1070 pg/mL (sensitivity: 91.8% and speciifcity 72.6%); with moderate renal injury was 7121 pg/mL (sensitivity: 80.2% and speciifcity: 89.7%); with severe renal injury was 33344 pg/mL (sensitivity: 83.3% and speciifcity: 80%).
Conclusion: Moderate to severe renal function injury could increase circulating level of NT-proBNP and therefore, the cut-off value of NT-proBNP for HF diagnosis should be elevated accordingly in patients of HF combing renal injury.

Objective To evaluate the status of lymph node micrometastases in "non-metastatic" No11P lymph nodes as judged by conventional pathology in the lower third of gastric cancer. Methods In this study 43 No11P lymph nodes harvested from 43 patients which was histologically free of metastasis were examined by consecutive sections and TRAP( telomeric repeat amplification protocol)-ELISA (enzyme linked immunosorbent assay). The data were statistically analyzed according to the clinicopathological features of the patients. Results Micrometastasis was discovered in 4 lymph nodes from 4 patients by consecutive sections. The micrometastatic rate of the conventional pathologic non-metastatic No11P lymph nodes was 9%. The micrometastatic rate of the conventional pathologic non-metastasis No11P lymph nodes detected by TRAP-ELISA was 44%, including 4 lymph nodes observed by consecutive sections It revealed that lymph nodes micrometastases were correlated with the size of the tumor( x2 = 8. 488, P < 0. 05 )、and tumor stage (x2 = 12. 022,P < 0. 05 ). It also showed that the micrometastatic rate increased proportionally to tumor infiltration depth(x2 =6. 473, P <0. 05), not correlated with patients' demographic features, general type and histological differentiation of the tumor. Conclusions There was a high rate of micrometastasis in No11P lymph nodes. This lymph nodes micrometastasis was correlated with the size of the tumor, invasion depth of primary tumor and patients' clinical stage.

Ulcerative colitis (UC)is a chronic non-specific inflammatory disease involving colon and rectum,and its etiology is not yet fully defined. UC is recurrent and can develop into colorectal cancer. Non-coding RNA (ncRNA)such as microRNA,long non-coding RNA (lncRNA),circular RNA (circRNA)plays a significant role in the process of growth and development of diseases. NcRNA can induce UC via promoting inflammatory cell infiltration,weakening intestinal mucosal barrier function and inducing intestinal epithelial cell apoptosis,and participate in its cancerization. This article reviewed the advances in study on role of ncRNA in UC.

OBJECTIVETo compare the clinical efficacy difference between acupuncture combined with rehabilitation and simple rehabilitation for foot drop after stroke.

METHODSNinety-eight patients were randomly divided into a combination group and a rehabilitation group, 49 cases in each one. Acupuncture and rehabilitation were used in the combination group. The acupoints were Yanglingquan (GB 34), Zusanli (ST 36), Guangming (GB 37), Xuanzhong (GB 39), Sanyinjiao (SP 6), etc., while rehabilitation included training for musculi hippicus strength and musculi triceps surae. Only the same rehabilitation was applied in the rehabilitation group. The treatment was given six times a week for continuous six weeks. Musculi hippicus force, shank triceps spasticity, toe flexion improvement and the maximum integral EMG (iEMG) of the musculi tibialis anterior and caput laterale musculi gastrocnemii were compared between the two groups,and the effects were evaluated.

RESULTSAfter treatment, the musculi hippicus force, iEMG of musculi tibialis anterior and caput laterale musculi gastrocnemii, the function scores of the lower limbs by Fugl-Meyer of the two groups were better than those before treatment (all<0.05), with the better effect in the combination group (all<0.05). And the scores of shank triceps tension were decreased in the two groups (both<0.05), more apparently for the combination therapy (<0.05). The improvement rate of toe flexion of the combination group was 87.76% (43/49), which was obviously higher than 69.39% (34/49) of the rehabilitation group (<0.05). The cured rate of the combination group was 48.98%(24/49), and it was better than 28.57% (14/49) of the rehabilitation group (<0.05).

CONCLUSIONSAcupuncture combined with rehabilitation achieves better effect than simple rehabilitation for foot drop after stroke.

Background:Rectal cancer is a common malignant tumor of alimentary tract.It has been demonstrated that oxaliplatin-based neoadjuvant chemotherapy is effective for rectal cancer,however,its mechanism is not fully clarified.Aims:To explore the effect of neoadjuvant chemnotherapy with FOLFOX4 (folinic acid,fluorouracil,and oxaliplatin) on expressions of Ki-67,a proliferating cell-associated nuclear antigen,matrix metalloproteinase-2 (MMP-2),and Fas,a death receptor in cancerous tissue of patients with rectal cancer.Methods:A total of 104 cases of patients with histologically proven rectal cancer from Aug.2014 to Feb.2016 at Central Hospital of China National Petroleum Corporation were enrolled prospectively and randomly allocated into treatment group (n =58) and control group (n =46).Patients in treatment group finished 6 cycles of neoadjuvant chemotherapy with FOLFOX4 before surgery,and those in control group underwent surgery directly.Expressions of Ki-67,MMP-2 and Fas protein in cancerous tissue of surgical specimens were determined immunohistochemically.Results:Immunoreactivity of Ki-67 mainly located in the nucleus of rectal cancer cells,and those of MMP-2 and Fas mainly located in the cytoplasm.Expression rates of Ki-67 and MMP-2 were significantly lower in treatment group than in control group (41.4％ vs.80.4％,P ＜ 0.05;36.2％ vs.73.9％,P ＜ 0.05),while those of Fas was significantly higher in treatment group than in control group (62.1％ vs.32.6％,P ＜ 0.05).Conclusions:The therapeutic effect of neoadjuvant chemotherapy with FOLFOX4 on rectal cancer might be associated with the inhibition of proliferative,invasive and metastatic capacities and induction of apoptosis in cancer cells.

Objective:To investigate the implementation status of sepsis hour-1 bundle strategy for patients with septic shock in emergency department.Methods:A total of 116 septic shock patients admitted to the emergency department from January 2020 to December 2020 were included in this prospective study, and the implementation of sepsis bundles and the clinical outcomes of patients were recorded.Results:Among 116 patients, 20 cases (17.2%) had lactic acid monitored within 1 h, 20 cases (17.2%) had blood culture before antibiotics, 82 cases (70.1%) received broad-spectrum antibiotics, 16 cases (13.8%) received fluid resuscitation ≥30 ml/kg, and 57 cases (49.1%) received vasoactive drugs during resuscitation. Finally, the sepsis hour-1 bundle strategy was fully implemented only in 13 cases (11.2%). Compared with the group with incomplete implementation of sepsis hour-1 bundle strategy, the volume of fluid recovery in the group with full implementation was significantly increased [33.7 (30.0,37.5) vs. 8.9(7.3,10.8) ml/kg, Z=-4.78, P<0.001], mean artery blood pressure significantly increased [70.0 (70.0,76.7) vs. 67.7 (61.7,76.7)mmHg(1 mmHg=0.133 kPa) , Z=-2.00, P<0.001], and lactic acid significantly decreased [3.0 (2.0,3.2) vs. 4.4 (3.7,7.2) mmol/L, Z=-2.76, P=0.006]. However, there were no significant differences in ICU mortality, in-hospital mortality and 28-day mortality between the two groups ( P>0.05). Conclusions:Septic shock patients in emergency department have poor compliance with the implementation of sepsis hour-1 bundle strategy, and relevant management training should be strengthened.

BACKGROUNDOncofetal protein high-mobility-group AT-hook protein 2 (HMGA2) is reactivated in serous ovarian cancer (SOC) and its overexpression correlates with poor prognosis. To explore the mechanism, we investigated whether HMGA2 could avoid microRNA regulation due to gene truncation or 3' UTR shortening by alternative polyadenylation.

METHODSReal-time reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate the abundance of different regions of HMGA2 mRNA in 46 SOC samples. Rapid amplification of cDNA 3' ends (3' RACE) and Southern blotting were used to confirm the shortening of 3' untranslated region (UTR). 5' RACE and Southern blotting were used to prove the mRNA decay.

RESULTSNo significant difference in the ratio of the stable coding region to the fragile region was observed between SOC and control normal fallopian tubes, indicating that the HMGA2 gene is not truncated in SOC. Varying degrees of 3' UTR shortening in SOC samples were observed by comparing the abundance of the proximal region and distal region of the HMGA2 3' UTR. The ratio of the proximal to the distal region of the 3' UTR correlated significantly with expression of the HMGA2 coding region in SOC (r = 0.579, P < 0.01). Moreover, although the abundance of the HMGA2 coding region varied, all samples, including the very low expressed samples, exhibit relatively high levels of the proximal 3' UTR region, suggesting a dynamic decay of HMGA2 mRNA from the 5' end. The shortening of 3' UTR and the decay from the 5' end were confirmed by 3' RACE, 5' RACE and subsequent Southern blotting.

CONCLUSIONHeterogeneous 3' UTR lengths render HMGA2 susceptible to different levels of negative regulation by microRNAs, which represents an important mechanism of HMGA2 reactivation in SOC.

3' Untranslated Regions ; genetics ; Cystadenocarcinoma, Serous ; genetics ; metabolism ; Female ; HMGA2 Protein ; genetics ; metabolism ; Humans ; Ovarian Neoplasms ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVE: To identify the problems in clinical radiotherapy planning for cervical cancer through quantitative evaluation of the radiotherapy plans to improve the quality of the plans and the radiotherapy process. METHODS: We selected the clinically approved and administered radiotherapy plans for 227 cervical cancer patients undergoing external radiotherapy at Sun Yat-sen University Cancer Center from May, 2019 to January, 2022. These plans were transferred from the treatment planning system to the Plan IQ^TM workstation. The plan quality metrics were determined based on the guidelines of ICRU83 report, the GEC-ESTRO Working Group, and the clinical requirements of our center and were approved by a senior clinician. The problems in the radiotherapy plans were summarized and documented, and those with low scores were re-planned and the differences were analyzed. RESULTS: We identified several problems in the 277 plans by quantitative evaluation. Inappropriate target volume selection (with scores < 60) in terms of GTV, PGTV (CI) and PGTV (V_{66 Gy}) was found in 10.6%, 65.2%, and 1% of the plans, respectively; and the PGTV (CI), GTV, and PCTV (D_98%, HI) had a score of 0 in 0.4%, 10.1%, 0.4%, 0.4% of the plans, respectively. The problems in the organs at risk (OARs) involved mainly the intestines (the rectum, small intestine, and colon), found in 20.7% of the plans, and in occasional cases, the rectum, small intestine, colon, kidney, and the femoral head had a score of 0. Senior planners showed significantly better performance than junior planners in PGTV (V_{60 Gy}, D_98%), PCTV (CI), and CTV (D_98%) (P≤0.046) especially in terms of spinal cord and small intestine protection (P≤0.034). The bowel (the rectum, small intestine and colon) dose was significantly lower in the prone plans than supine plans (P < 0.05), and targets coverage all met clinical requirements. Twenty radiotherapy plans with low scores were selected for re-planning. The re-planned plans had significantly higher GTV (D_min) and PTV (V_{45 Gy}, D_98%) (P < 0.05) with significantly reduced doses of the small intestines (V_{40 Gy} vs V_{30 Gy}), the colon (V_{40 Gy} vs V_{30 Gy}), and the bladder (D_35%) (P < 0.05). CONCLUSION Quantitative evaluation of the radiotherapy plans can not only improve the quality of radiotherapy plan, but also facilitate risk management of the radiotherapy process.
Humans ; Female ; Uterine Cervical Neoplasms/radiotherapy* ; Rectum ; Colon ; Kidney ; Organs at Risk

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.