[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

OBJECTIVES: To evaluate the inhibitory effect of oridonin against proliferation of pancreatic cancer cells and the mechanism underlying the synergistic effect of low-intensity pulsed ultrasound (LIPUS). METHODS: PANC-1 cells treated with different concentrations of oridonin were examined for changes in cell proliferation using CCK-8 assay and in MDA, GSH and ATP levels using flow cytometry. The protein expressions of GPX4, Nrf2 and HO-1 in the treated cells were detected with Western blotting. The effect of Fer-1, a ferroptosis inhibitor, on proliferation of oridonin-treated cells were assessed, and the effects of oridonin combined with LIPUS on PIEZO1 protein expression was evalauted using Western blotting. A C57BL/6J mouse model bearing pancreatic cancer cell xenograft was established and treated with oridonin, LIPUS, or both, and the histological changes in the tumor tissues and tumor cell proliferation were examined with HE staining and immunohistochemistry for Ki67; the changes in GPX4 expression in the tumor tissues were detected using Western blotting and immunofluorescence staining. RESULTS: In PANC-1 cells, oridonin treatment significantly inhibited cell proliferation, increased intracellular Fe²⁺, ROS, and MDA levels, and decreased GSH and ATP levels. Oridonin also resulted in lowered GPX4 and increased HO-1 and Nrf2 protein expression levels in the cells. The combined treatment with LIPUS signficiantly enhanced the inhibitory effect of oridonin on PANC-1 cell viability in vitro and on xenograft growth in the mouse models, resulting also in more obvious reduction of the intensity of Ki67 staining and GPX4 protein expression and more pronounced increase of PIEZO1 protein expression in the tumor tissues in the mouse models. CONCLUSIONS LIPUS enhances the effect of oridonin to promote ferroptosis of pancreatic cancer cells by activating PIEZO1 through the Nrf2/HO-1/GPX4 pathway.
Ferroptosis/drug effects* ; Animals ; Pancreatic Neoplasms/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Humans ; Cell Line, Tumor ; Mice ; Heme Oxygenase-1/metabolism* ; Diterpenes, Kaurane/pharmacology* ; Cell Proliferation/drug effects* ; Mice, Inbred C57BL ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Ion Channels/metabolism* ; Ultrasonic Waves ; Signal Transduction

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.

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

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.

Objective:To investigate and analyze the current situation, screening, clinical characteristics, prevention and treatment of bleeding esophageal varices in cirrhotic patients with portal hypertension in Tibet region.Methods:Clinical data of cirrhotic patients with portal hypertension through March 2017 to February 2020 from Tibet region were collected and analyzed retrospectively.Results:511 cases with liver cirrhosis were included in the study, of which 185 cases (36.20%) had compensated cirrhosis and 326 cases (63.80%) had decompensated cirrhosis. Further analysis of the etiological data of liver cirrhosis showed that 306 cases (59.88%) were of chronic hepatitis B, 113 cases (22.11%) of alcoholic liver disease, and 68 cases (13.31%) of chronic hepatitis B combined with alcoholic liver disease. Among patients with compensated liver cirrhosis, 48 cases (25.95%) underwent endoscopic examination of which 33 diagnosed as high-risk variceal bleeding. However, none of these 33 cases had received non-selective β-blocker therapy, and only four patients had received endoscopic variceal banding therapy. Among patients with decompensated liver cirrhosis, 83 cases (25.46%) had a history of upper gastrointestinal bleeding, 297 cases (91.10%) had ascites, 23 cases (7.05%) had hepatic encephalopathy, and 3 cases (0.92%) had hepatorenal syndrome. Among the patients with a history of upper gastrointestinal bleeding, 42 cases (50.60%) had received secondary preventive treatment for bleeding esophageal varices, including 39 cases of endoscopic treatment, 1 case of endoscopic combined drug treatment, 3 cases of interventional treatment, and 2 cases of surgical treatment.Conclusion:Chronic hepatitis B and alcoholic liver diseases are the main causes of liver cirrhosis in Tibet region. Moreover, this region lacks screening, prevention and treatment for bleeding esophageal varices in cirrhotic patients with portal hypertension. Therefore, it is necessary to increase the screening of high-risk groups to prevent and improve the first-time bleeding, and promote multidisciplinary team to prevent and treat re-bleeding.

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.

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 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.

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.