Objective To construct a ferroptosis-related glioblastoma (GBM) recurrence risk model and evaluate the prognosis of patients. Methods Differentially expressed genes (DEGs) related to ferroptosis in recurrent GBM were screened by CGGA and FerrDb databases. Key genes were obtained by Lasso regression. Then, nomogram was constructed according to the key risk genes, and the prediction efficiency was verified using the TCGA database. GO, KEGG, and GSEA databases were used in exploring the mechanism of prognosis. ESTIMATE and TIMER were used in studying tumor immune infiltration and the expression of immune check points. Results WWTR1, PLIN2, and BID were important prognostic factors for GBM recurrence. The nomogram was constructed according to gender and age, and the observed values were in good agreement with the predicted values. The AUC values were 0.65 (1 year), 0.66 (3 years), and 0.63 (5 years) for CGGA and 0.68 (1 year), 0.76 (3 years), and 0.79 (5 years) for TCGA. Epithelial mesenchymal transition, KRAS pathway, and inflammatory response were significantly upregulated in the high-risk subtypes (P < 0.05). Immune cell infiltration was lower (P < 0.05). Risk score was positively correlated with the expression of immunosuppression check points. Conclusion Ferroptosis-related genes WWTR1, PLIN2, and BID can be used in constructing a nomogram with good predictive performance. These risk genes may affect prognosis through tumor-infiltrating immune cells and immune check points.

BACKGROUNDIt has been found that cardiac protection afforded by ischemic preconditioning (IPC) is significantly reduced in the senescent myocardium. ADAMTS-1 (a disintesrin and metalloprotease with thrombospondin type 1 motifs) has been shown to inhibit angiogenesis in a variety of in vitro and in vivo assays. The aim of this study was to investigate the age-associated differences in ADAMTS-1 protein expression in rat myocardium after ischemic preconditioning.

METHODSSixty-four young (4 months) and old (24 months) male Sprague-Dawley rats were randomly assigned to an IPC group (40 rats) or a sham group (rats). A model of delayed IPC was induced and rats were sacrificed and myocardial samples were harvested from the ischemic-reperfused region for immunohistochemical detection of ADAMTS-1 at serial time points after IPC. A model of myocardial infarction was produced by ligation of the left anterior descending coronary artery in additional sets of young and old rats after sham or IPC procedures, then age-associated myocardial infarction survival after IPC was calculated.

RESULTSADAMTS-1 expression increased significantly in old rats compared to young rats (P < 0.05). The mean densities of ADAMTS-1 protein at 0, 6, 12, and 24 hours in young-IPC group after IPC were 0.05 ± 0.01, 0.13 ± 0.03, 0.16 ± 0.04, and 0.12 ± 0.03 vs. 0.07 ± 0.03, 0.20 ± 0.03, 0.24 ± 0.05, and 0.21 ± 0.04 in old-IPC group. IPC resulted in diminished survival rates (5/35 vs. 6/14, old-IPC group vs. old-sham group, P < 0.05), reduced left ventricular fractional shortening ((13.9 ± 2.8)% vs. (18.3 ± 2.3)%, P < 0.05) and increased the myocardial infarction size ((37.9 ± 3.2)% vs. (32.8 ± 5.1)%, P < 0.05) in the older rats.

CONCLUSIONSCardioprotection with IPC is attenuated in the older heart. ADAMTS-1 expression induced by IPC is greater in old rats. Over-expression of anti-angiogenic factors might be a potential mechanism behind reduced protection after IPC associated with aging.

ADAM Proteins ; metabolism ; ADAMTS1 Protein ; Aging ; metabolism ; physiology ; Animals ; Immunohistochemistry ; Ischemic Preconditioning, Myocardial ; Male ; Myocardial Infarction ; metabolism ; pathology ; Myocardium ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo assess the association between single nucleotide polymorphisms (SNPs) of melanocortin-1 receptor gene (MC1R) and freckles in Chinese Han population from Chengdu.

METHODSTwenty randomly selected samples were used to select SNPs of the MC1R gene through DNA sequencing. Pyrosequencing in combination with DNA pooling technique was used to assess allelic frequencies of the selected SNPs in 111 individuals with freckles and 124 normal controls. Representative SNPs were selected based on their functional implications and minimum allele frequency (MAF> 0.05). Genotype of the SNPs were determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or pyrosequencing.

RESULTSBased on results of DNA sequencing and pyrosequencing, 4 SNPs (rs2228479, rs885479, rs33932559 and rs2228478) were selected to determine the genotype for each sample. Comparison of genotypic and allelic frequencies of the 4 SNPs with χ (2) test has found no significant difference between the two groups (P> 0.05). For rs33932559, the frequencies of T allele were respectively 90.09% and 91.94% for individuals with freckles and normal controls. For rs2228479 and rs2228478, the frequencies of G and A allele were both about 77%. For rs885479, the frequency of T allele was about 60%. None of the above 3 SNPs showed a significant difference between the two groups in terms of allelic or genotypic frequencies.

CONCLUSIONNo association between the selected SNPs of MC1R gene has been found with development of freckles for the selected Chinese Han population from Chengdu.

Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; China ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Melanosis ; genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Receptor, Melanocortin, Type 1 ; genetics ; Young Adult

OBJECTIVETo observe the influence on prognosis and possible side-effects of arginine in

METHODSMulti-center clinical trial, randomized double blinded patients with severe trauma and burns. and placebo control methods were employed in the study. Eighty-six patients with severe trauma and burns were randomly divided into control (C, n = 45) and arginine treatment (Arg, n = 41) groups. The patients in Arg group received arginine in dose of 0. 4 g x kg(-1) x d(-1) orally, while those in C group received same dose of placebo (tyrosine) for 7 days. All the patients in both groups were given diet with equal calories and equal nitrogen content. The changes in the wound healing time, hospital stay, and the incidence of side-effects of the medication in both groups of patients were observed and compared before and after the supplementation of arginine.

RESULTSThe wound healing time and hospital stay days of severe trauma patient in Arg group (n = 29) were 11. 1+/-2. 8 d and 19+/-6 d, which were all obviously shorter than those in C group (13. 2+/-5. 5 d, 22 +/-6 d, n =33, P <0.05). On the other hand, in severe burn patients there were no significant difference of the wound healing time (20+/-5 d vs 22+/-8 d, n = 12, P > 0. 05) and hospital stay days (28+/-6 d vs 29+/-8 d, n = 12, P >0. 05) between the Arg and C groups. In addition, in C and Arg groups, the occurrence of the side-effects were seldom (2. 44% vs 2. 22% , P = 1. 000) and it disappeared when the supplementation of drugs was stopped.

CONCLUSIONOral feeding of arginine is beneficial in enhancing wound healing, reduction of hospital stay days in severe trauma patients and with little side-effects, but it is not beneficial to improve the prognosis of severe burn patients. Maybe this is due to inadequate number of case involved in the study.

Administration, Oral ; Adolescent ; Adult ; Aged ; Arginine ; administration & dosage ; adverse effects ; therapeutic use ; Burns ; diagnosis ; drug therapy ; Double-Blind Method ; Female ; Humans ; Length of Stay ; Male ; Middle Aged ; Prognosis ; Wound Healing

OBJECTIVETo evaluate the amplification rate and the lowestlower detection limit of an in-house HIV-1 Drug resistant (HIVDR) genotyping test.

METHODSA total of 30 plasma samples were selected, which covered all major HIV-1 subtypes predominating prevailing in China (B', CRF07_BC, CRF01 _AE). The viral loads of the 30 selected samples were detected in triplicate by Easy Q method and the average values were taken as the viral loads of the samples. Each sample was diluted to the concentration of > 1000 copies/ml, 401-1000 copies/ml, 101-400 copies/ml, 50-100 copies/ml and < 50 copies/ml with HIV-negative plasma. After extraction of nucleic acids, RT-PCR and nested PCR amplification were performed, the efficiency of amplification of each subtype and the minimum detection limit were determined statistically based on the PCR results.

RESULTSThe viral loads of the selected samples ranged from 2.03 x 10(2)-5.92 x 10(4) copies/ml. The sample of 50-1000 copies/ml have a high amplification rate (86%).

CONCLUSIONThe In-house method for HIV-1 drug resistance genotyping has a high sensitivity with a high successful amplification rate, especially in the samples with low viral load. This method can be used to the detection of drug-resistant virus and to provide scientific data to treatment options for patients.

China ; Drug Resistance, Viral ; Genotype ; HIV-1 ; classification ; drug effects ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Viral Load

Adult ; Aged ; Esophageal and Gastric Varices ; diagnosis ; surgery ; Female ; Humans ; Male ; Middle Aged ; Pancreas ; pathology ; surgery ; Pancreatic Neoplasms ; diagnosis ; surgery ; Splenomegaly ; diagnosis ; surgery ; Young Adult

Objective To explore the possible role of voltage-gated potassium channel-interacting protein 1 (KChIP1) in the pathogenesis of epilepsy. Methods Sprague Dawley female adult rats were treated with pentylenettrazole (PTZ) to develop acute and chronic epilepsy models. The approximate coronal sections of normal and epilepsy rat brain were processed for immunohistochemistry. Double-labeling confocal microscopy was used to determine the coexistence of KChIP1 and gamma-aminobutyric acid (GABA). Results KChIP1 was expressed abundantly throughout adult rat brain. KChIP1 is highly co-localize with GABA transmitter in hippocampus and cerebral cortex. In the acute PTZ-induced convulsive rats, the number of KChIP1-postive cells was significantly increased especially in the regions of CA1 and CA3 (P < 0.05); whereas the chronic PTZ-induced convulsive rats were found no changes. The number of GABA-labeled and co-labeled neurons in the hippocampus appeared to have no significant alteration responding to the epilepsy-genesis treatments. Conclusion KChIP1 might be involved in the PTZ-induced epileptogenesis process as a regulator to neuronal excitability through influencing the properties of potassium channels. KChIP1 is preferentially expressed in GABAergic neurons, but its changes did not couple with GABA in the epileptic models.

OBJECTIVETo observe the therapeutic effect and influential factors of strong stimulation of acupoints around eyes by reducing method of twisting the needle for treatment of adolescent myopia, and to compare the different curative effects of both weak and strong stimulus intensities and wearing glasses in daytime.

METHODSAccording to the principle of knowing and permission, the patients were divided into a strong stimulation group (60 cases, 120 eyes), a weak stimulation group (60 cases, 120 eyes) and a wearing glasses group (60 cases, 120 eyes). Both the strong stimulation group and the weak stimulation group were treated by reducing method of twisting the needle, with Cuanzhu (BL 2), Yuyao (EX-HN 4), Sizhukong (TE 23), Sibai (ST 2) and Taiyang (EX-HN 5) selected. Each acupoint was twisted 360 and 90 times per min for the strong stimulation group, and 90 degrees and 60 times per min for the weak stimulation group; the wearing glasses group were not treated with acupuncture, but with wearing glasses in daytime.

RESULTSAfter treatment with the reducing method of twisting the needle, the vision improved (P < 0.01), with more obviously increased in the strong stimulation group than the weak stimulation group (P < 0.01), and there was no significant change of vision in the wearing glasses group. The age and the myopic degree of the patient before treatment were closely related with the change of vision after treatment (P < 0.01).

CONCLUSIONThe reducing method of twisting the needle has a definite clinical therapeutic effect on adolescent myopia; strong stimulation has a better effect than the weak one; the age and the myopic degree of the patient possibly influence the therapeutic effect.

Acupuncture Points ; Acupuncture Therapy ; methods ; Adolescent ; Child ; Female ; Humans ; Male ; Myopia ; therapy

OBJECTIVE: To explore the effect of continuous low-dose infusion of esmolamine on intraoperative dosage of opioids and awakening quality in general anesthesia in pediatric surgeries. METHODS: A total of 100 children (6-8 years of age) undergoing pediatric surgery under general anesthesia were randomized equally into observation group and control group.In the observation group, the children received an intravenous injection of 0.1mg/kg esmolamine 10 min before induction of general anesthesia, followed by intravenous infusion of esmolamine at 2 μg•kg^-1•min^-1 until the end of the operation; those in the control group were infused with the same volume of normal saline instead of esmolamine in the same manner.The dosage of remifentanil during operation, recovery time of spontaneous breathing, recovery time of consciousness and extubation time were recorded in all the cases.The VAS score at 15, 30 and 60 min after extubation were assessed, and intravenous injection of naborphine 0.3 mg/kg was given for a VAS score ≥4;the total dosage of naborphine and adverse events were recorded for all the patients. RESULTS: The total dose of remifentanil was significantly lower in the observation group than in the control group, but the spontaneous respiratory recovery time, consciousness recovery time and extubation time did not differ significantly between the two groups.The VAS scores at 15, 30 and 60 min after extubation were all better in the observation group than in the control group; the total intraoperative dose of naborphine was significantly lower in the observation group. CONCLUSION Continuous infusion of low-dose esmolamine during pediatric surgery can effectively lower intraoperative dosage of opioids and reduce pain during recovery without affecting the quality of awakening.
Child ; Humans ; Remifentanil ; Anesthesia, General ; Analgesics, Opioid

Objective:To investigate the long-term efficacy and complications of augmentation uretero-enterocystoplasty (AUEC).Methods:The clinical data of 262 patients with lower urinary tract dysfunction who underwent AUEC at our center from January 2003 to June 2022 were analyzed retrospectively. There were 193 males and 69 females, the median age was 24 (4, 67) years, the median disease duration was 12.0 (0.2, 56.0) years and the preoperative creatinine was 91.5 (68.1, 140.0) μmol/L. 320 ureters had high-grade UUTD, 216 ureters had VUR, 14 of which had low-pressure reflux.The number of low-grade VUR ureter was 22 (10.2%) and the number of high-grade VUR ureter was 194 (89.8%). Video-urodynamics showed that the maximum bladder capacity was 102 (47, 209) ml, the maximum detrusor pressure was 33.0 (15.5, 50.5) cmH 2O, and the bladder compliance was 6.4 (3.0, 12.3) ml/cmH 2O. All patients underwent AUEC. The surgical method is to cut a segment of sigmoid colon, open the sigmoid colon along the mesenteric margin, fold and suture it into " U" or " S" shaped intestinal mesh according to the principle of " detubulization" . At the same time, perform ureteroplasty and replanting, and then anastomosis the intestinal mesh with the opened bladder flap to form an expanded new bladder. Follow-up was performed via outpatient clinic or telephone. The creatinine, maximum bladder capacity, maximum detrusor pressure, bladder compliance, ureteral reflux and upper urinary tract dilatation were compared preoperatively and postoperatively. The postoperative complications were also evaluated. Results:The median follow-up time was 57.4 (4, 151) months after surgery. At 1-3 months after surgery, the maximum bladder capacity and bladder compliance increased to 303.9% and 189.9% of the preoperative level, and the maximum detrusor pressure decreased to 63.6% of the preoperative level. At 6-10 years after surgery, the maximum bladder capacity and bladder compliance increased to 490.2% and 627.9% and the maximum detrusor pressure decreased to 25.8% of the preoperative level. The UUTD of the patients was significantly reduced after surgery. The number of the high grade UUTD decreased to 116 (116/398, 29.2%) at 1-3 months and 51 (51/274, 18.6%) at 4-6 months. At 6-10 years, the number of the high-grade UUTD decreased to 4 (4/76, 5.3%) ( P<0.001), which was significantly lower than that before operation. The VUR was significantly relieved after operation, and 393 ureters had no VUR at 1-3 months, accounting for 97.8% (393/402) of the total ureters. Sustained remission of VUR was observed during follow-up. 73 ureters had no VUR at 6-10 years, accounting for 96.1% (73/76) of total ureters ( P<0.001). Patients' creatinine decreased to 79.0 (65.0-128.2) μmol/L at 1-3 months postoperatively, with a downward trend but no statistical difference, and creatinine levels were not significantly elevated at any postoperative time point compared with preoperative levels ( P>0.05). Postoperative complications included metabolic acidosis in 26 cases (9.9%), vesicoureteral anastomosis stenosis in 15 cases (5.7%), recurrent urinary tract infection in 16 cases (6.1%), and urinary calculi in 20 cases (7.6%), and intestinal obstruction requiring laparotomy in 8 cases (3.1%), all of them could be improved after treatments. Conclusions:AUEC is a safe and effective method for treating high-grade VUR or VUR with impaired anti-reflux mechanism, high-grade UUTD or UUTD with ureteral or vesicoureteral junction obstruction, and all of the complications can be improved after treatment. This technique can increase the bladder capacity and compliance, reconstruct the anti-reflux mechanism, and release upper urinary tract obstruction. It may play an important role in stabilizing and protecting the residual renal function from further deterioration.