Objective To investigate the regulatory effects and molecular mechanisms of PUS3 on GBM cell malignant behaviors(proliferation,apoptosis,invasion)in vitro,providing potential therapeutic targets for GBM.Methods The expression of PUS3 in GBM was analyzed using the GEPIA2 database.Kaplan-Meier survival analysis evaluated the survival difference between PUS3 high-and low-expression patients.qRT-PCR and Western blot were performed to detect PUS3 expression in normal glial cells(HEB)and GBM cell lines(U87,LN229,U251,T98G).PUS3-stably overexpressing GBM cell lines were constructed.Colony formation,CCK-8 assay,and flow cytometry were used to assess proliferation and apoptosis.Transwell assay evaluated cell invasion.Immunohis-tochemistry(IHC)detected PUS3 expression in GBM patient tissues.Western blot analyzed tumor-related pathway proteins after PUS3 overexpression.Results The expression level of PUS3 is elevated in GBM patient tissues,and the mRNA and protein expression levels in GBM cells are significantly higher than those in HEB cells(P<0.01).After overexpression of PUS3,the proliferation ability of GBM cells was enhanced(P<0.05),the apoptosis rate decreased(P<0.01),and the number of invasive cells increased(P<0.001).Mechanistically,overexpression of PUS3 significantly activates the AKT pathway,and the use of AKT inhibitors in PUS3 overexpressing cells can reverse the pro cancer effect.Conclusion PUS3 is highly expressed in glioblastoma(GBM)and promotes tumor cell proliferation,invasion,and apoptosis inhibition by activating the AKT pathway,suggesting its potential as a therapeutic target for GBM treatment.

Objective To investigate the regulatory effects and molecular mechanisms of PUS3 on GBM cell malignant behaviors(proliferation,apoptosis,invasion)in vitro,providing potential therapeutic targets for GBM.Methods The expression of PUS3 in GBM was analyzed using the GEPIA2 database.Kaplan-Meier survival analysis evaluated the survival difference between PUS3 high-and low-expression patients.qRT-PCR and Western blot were performed to detect PUS3 expression in normal glial cells(HEB)and GBM cell lines(U87,LN229,U251,T98G).PUS3-stably overexpressing GBM cell lines were constructed.Colony formation,CCK-8 assay,and flow cytometry were used to assess proliferation and apoptosis.Transwell assay evaluated cell invasion.Immunohis-tochemistry(IHC)detected PUS3 expression in GBM patient tissues.Western blot analyzed tumor-related pathway proteins after PUS3 overexpression.Results The expression level of PUS3 is elevated in GBM patient tissues,and the mRNA and protein expression levels in GBM cells are significantly higher than those in HEB cells(P<0.01).After overexpression of PUS3,the proliferation ability of GBM cells was enhanced(P<0.05),the apoptosis rate decreased(P<0.01),and the number of invasive cells increased(P<0.001).Mechanistically,overexpression of PUS3 significantly activates the AKT pathway,and the use of AKT inhibitors in PUS3 overexpressing cells can reverse the pro cancer effect.Conclusion PUS3 is highly expressed in glioblastoma(GBM)and promotes tumor cell proliferation,invasion,and apoptosis inhibition by activating the AKT pathway,suggesting its potential as a therapeutic target for GBM treatment.

Objective To establish an optimal limiting dose for dose limiting rings placed in the anterior and posterior regions of the neck for reducing head and neck lymphedema under intensity-modulated radiation therapy(IMRT)for early nasopharyngeal carcinoma(NPC)from a dosimetric perspective.Method Fifteen newly diagnosed early-stage nasopharyngeal carcinoma patients who underwent CT localization for radiotherapy at the Cancer Hospital of Guangzhou Medical University from January to September 2022 were included in the study.Each case was designed with five sets of radiotherapy plans.Plan A consisted of conventional unlimited-field plans,while Plans B-E consisted of limited-field plans with dose constraints set at 20,18,16,and 14 Gy,respectively,with the remaining parameters consistent with Plan A.The impact on target coverage and organ-at-risk constraints was evaluated through variance analysis and pairwise multiple comparisons using a randomized block design to determine the optimal dose limits.Results The gradient of 16Gy was determined as the optimal dose limiting cutoff point for achieving the balance between target coverage and organ limiting dose.Compared with the conventional plan,The plans with the placement of a cervical anterior and posterior dose limiting ring(16Gy)did not change the target dose coverage(P>0.05),but only yielded a slight change in the homogeneity index(P<0.05).It did not cause any changes of the dosage in the inner ear,mandible,and brainstem(all P>0.05),but lead to statisti-cally significant reductions in the oral cavity,throat,and thyroid(all P<0.05).It caused a slight increase of the dose in the parotid gland and spinal cord(both P<0.05),but the increased dose was anyhow within the tolerance range.Conclusion The dosimetric investigation determines an optimal dose limit cutoff point for the cervical ante-rior and posterior dose limiting rings.It is expected to provide a design method for IMRT plans to reduce head and neck lymphedema after radiotherapy for early NPC.

High-altitude regions,characterized by their elevated altitude,are subject to a complex set of environmental conditions including intense ultraviolet radiation,low oxygen levels,low temperatures,and low humidity.These distinctive environmental features lead to unique dietary patterns,lifestyles,and physiological adaptations.Notably,individuals who have just moved into high-altitude areas and those who live there on a long-term basis undergo specific adaptive adjustments in glucose metabolism.Typically,newcomers experience transient elevations in blood glucose levels,which gradually decline after prolonged residence at high altitudes to levels even lower than those found at low altitudes.In general,current findings of observational studies generally suggest a decreased risk of diabetes mellitus among populations inhabiting high-altitude regions.However,the glucose metabolism varies among populations from different high-altitude regions across the world,which indicates that the reshaping of glucose metabolism induced by high altitudes is a complicated phenomenon.This article provides an overview of the impact of various components of high-altitude environment,characteristic lifestyle factors,and socioeconomic development levels on glucose metabolism and the related diseases and the potential mechanisms involved.The aim is to offer valuable insights for researchers investigating glucose metabolism in high-altitude settings.

Objective To investigate the safety and short-term efficacy of π-shaped anastomosis and circular anastomosis(reverse puncture device)in reconstruction of esophagojejunostomy after laparoscopic total gastrectomy.Methods A retrospective study was used to collect the clinical and pathological data of 75 cases of gastric cancer from January 2019 to March 2021.According to the different reconstruction methods of esophagojejunal anastomosis,the patients were divided into a linear cutting obturator group(π-shaped anastomosis group,n = 27)and a circular anastomat anastomosis group(reverse puncture device group,n = 48).The general information of the two groups,operation time,esophagojejunostomy time,intraoperative bleeding volume,number of intraoperative lymph node dissection,intraoperative complications,and postoperative complications were compared and analyzed.Results The operation time and esophagojejunostomy time in the π-shaped anastomosis group were(221.5±8.8)and(34.7±3.7)min,and the reverse puncture device group were and(246.9±5.6)and(47.2±4.6)min,respectively,the differences were statistically significant(t = 15.19,t = 11.81,P＜0.05).There were no statistical significance in the comparison of intraoperative bleeding volume and number of intraoperative lymph node dissection between the two groups(P＞0.05).In the reverse puncture device group,there were two intraoperative complications,including one case of esophageal jejunal anastomosis atresia and one case of anastomosis tear,postoperative complications occurred in 3 cases,postoperative anastomotic stenosis occurred in 2 case,and anastomotic bleeding occurred in 1 case.Conclusion Laparoscopic total esophagojejunostomy with π-shaped anastomosis and reverse puncture device are safe and feasible.In terms of esophagojejunostomy time,π-shaped anastomosis reconstruction time is shorter.When the small intestine diameter is relatively small and it is difficult to extend into the 25 mm stapler,the advantage of π-shaped anastomosis is more obvious.When the tumor is Siewert type Ⅰ and type Ⅱ adenocarcinoma of gastroesophageal junction,which infiltrates into above the dentate line,reverse puncture device method is recommended for reconstruction.

Objective:To uncover the effect of circ0025847 on the proliferation of colorectal cancer cells and its molecular mechanisms.Methods:qRT-PCR was utilized to analyze the expression of circ0025847 and QK1 in human colorectal cancer cells (HCT116, SW480) and normal mucosa cells (NCM460) .CCK-8 was used to analyze the effect of circ0025847 and QK1 on proliferation in colorectal cancer cells. Bioinformatics method was used to screen RBP which could bind to circ0025847. RNA pulldown and RIP was utilized to confirm whether QK1 binds to circ0025847.Effects of circ0025847 over-expression on QK1 expression was analyzed by Western blot.NC group, circ0025847 overexpression group and circ0025847 overexpression+ QK1 inhibitor group were established and the proliferation effect was determined by CCK8.Results:circ0025847 (the expression levels in NCM460, HCT116 and SW480 cells were 1.01±0.05, 0.49±0.08, 0.45±0.10) and QK1 (the expression levels in NCM460, HCT116 and SW480 cells were 0.98±0.07, 0.50±0.07, 0.47±0.09) expression was significantly downregulated in colorectal cancer cells. Overpression of circ0025847 and QK1 suppressed colorectal cancer cells growth.RNA pull-down and RIP clarified that circ0025847 bind to QK1 and circ0025847 positively regulate QK1 expression (7 199.20±12.44 VS 3 889.80±11.03) . circ0025847 inhibiting the proliferation of colorectal cancer cells by promoting the expression of QK1 was confirmed by rescue experiment.Conclusion:circ0025847 inhibits colorectal cancer cells proliferation via positively regulating QK1 expression, indicating that circ0025847 may be potential therapeutic target of colorectal cancer.

Vascular cognitive impairment (VCI) is a clinical syndrome with impairment of at least one cognitive domain caused by vascular risk factors or cerebrovascular diseases, and its pathogenesis is not completely clear so far. Microglia are innate immune cells in the brain. They participate in many processes such as neuroinflammation, synaptic pruning, myelin regeneration, neurogenesis and connection. They are associated with the occurrence and development of various neurological diseases such as cerebral infarction, Alzheimer's disease, Parkinson's disease, and autism. Recent studies have shown that microglia play an important role in the development of VCI. This article reviews the role of microglia in VCI.

[Abstract] Objective: To investigate the effect of Beclin1 knockdown on cisplatin resistance in ovarian cancer A2780 cells and its related mechanisms. Methods: The mRNA and protein expressions of Beclin1 in A2780 cells and drug resistant A2780/DDP cells were determined by qPCR and Western blotting. After transfection with Beclin1 siRNA, the sensitivity of A2780/DDP cells to cisplatin was detected by MTT assay; Cell clone formation and apoptosis were detected by the Colony formation assay and Flow cytometry assay, respectively; cell autophagy was monitored by monodansylcadaverin (MDC) staining. Furthermore, the protein levels of cell autophagy related proteins, lysosomal associated membrane protein Lamp-2 and Cathepsin B were detected by Western blotting. Results: The mRNA and protein expression levels of Beclin1 in cisplatin-resistant A2780/DDP cells were significantly higher than those in A2780 cells (all P<0.05). The expression of Beclin1 was significantly increased in A2780 cells after treated with cisplatin (P<0.05). Beclin1 knockdown promoted cisplatin induced apoptosis of A2780/DDP cells (P<0.05), inhibited autophagy and cell colony formation (all P<0.05), and increased cell sensitivity to cisplatin (P<0.05). Meanwhile, Western blotting showed that Beclin1 knockdown increased the protein levels of cleaved-caspase 3 and Cathepsin B in A2780/DDP cells, while down-regulated the protein expressions of Atg3, Atg7, LC3Ⅱ/Ⅰand Lamp-2 (all P<0.05). Conclusion: Beclin1 knockdown can improve the sensitivity of A2780/DDP cells to cisplatin, and the mechanism may be related to the inhibition of protective autophagy of cells by regulating the expressions of autophagy related proteins, and the regulation of lysosomes, thus further promoting cisplatin-induced apoptosis of drug-resistant cells.

Objective To investigate the regularity and predictors of weight loss during concurrent chemo-radiotherapy for nasopharyngeal carcinoma patients. Methods A retrospective study was carried out on 82 patients with nasopharyngeal carcinoma ,with average age of 45 years ,who received concurrent chemoradiotherapy at the Affiliated Cancer Hospital of Guangzhou Medical University. Paired t-test was used to analyze the weight loss pattern during chemoradiotherapy. The Spearman′s rank correlation analysis was used to investigate the correlation between high weight loss(HWL)and the clinical factors. Results The paired t-test showed that the weight of the patients decreased continuously every week during chemoradiotherapy(P < 0.05),and the value dropped most significantly during the 4th week. Among these 82 patients,32 were determined as HWL(weight loss > 10%). Spearman′s rank correlation analysis showed that HWL was associated with older age,female,higher T and TNM stage,3D-CRT technology,the higher dose of radiotherapy in nasopharynx and in neck lymph node,and decreases of leukopenia and hemoglobin over degree Ⅱ(P<0.05). Conlousions Weight may decrease continuously every week during chemoradiotherapy for nasopharyngeal carcinoma patients. Age,gender,T stage,TNM stage,radio-therapy dose,and leukopenia and hemoglobin decreases may be predictors for weight loss degree during concurrent chemoradiotherapy for nasopharyngeal carcinoma patients.

Objective To determine the effect of omental flap wrapping of pancreaticoduodenectomy on postoperative pancreatic fistula and intra-abdominal bleeding in patients undergoing pancreaticiduodenectomy through meta-analysis of published studies.Methods Articles about whether omental flap wrapping could prevent postoperative pancreatic fistula and intra-abdominal bleeding were searched in databases of MEDLINE,PUBMED and EMBASE.14 English article were found and according to including and excluding criteria,4 eligible articles with a total of 2971 patients were selected.Random effects model was used to analyze odds ratios and 95％ confidence intervals (CIs).Results 1129 patients were in omental wrapping group,and 1842 patients in nonomental wrapping group.Omental roll-up during pancreaticoduodenectomy could not prevent postoperative pancreatic fistula (OR =0.81,95 ％ CI 0.40～1.63,P＞0.05) or postoperative abdominal bleeding (OR=0.67,95％ CI 0.28～1.59,P＞0.05).The sensitivity analysis showed the pancreatic fistula rate was lower in the nonomental roll-up group than that in the omental roll-up group (OR=1.24,95％ CI 1.03～1.50,P＜0.05).Conclusions Omental wrapping can not decrease the risk of pancreatic fistula and abdominal bleeding after pancreaticoduodenectomy.Further randomized controlled trials are needed to identify the effect of omental wrapping technique for pancreaticoduodenectomy.