Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.

Based on the long bud stage phenotype of a new Lonicera japonica Flos variety "Huajin 6", using "Huajin 6" and "Da Mao Hua" as materials, probing the mechanism of its phenotype formation. Detection of endogenous Jasmonic acid hormones (JAs) content; the genes related to jasmonic acid (JA) synthesis were identified by transcriptome analysis of Lonicera japonica; flower buds and flowers of "Huajin 6" and "Da Mao Hua" were collected at different periods, and the qRT-PCR (quantitative real-time PCR) technique was used to analyze the trend of the expression of synthesis-related enzyme genes in Lonicera japonica Flos during the bud stage. The study found that the content of JAs in "Huajin 6" Lonicera japonica Flos was significantly lower than that in "Da Mao Hua"; applying exogenous methyl-jasmonate (MeJA) to "Huajin 6" can restore its flowering phenotype, making it close to wild type Lonicera japonica Flos; there are significant differences in the expression of two allene oxide synthase genes (AOS), three lipoxygenase genes (LOX), and two allene oxide cyclase genes (AOC) in the flowers and buds of "Huajin 6" and "Da Mao Hua" at different periods. It is hypothesized that the low expression of JA synthesis-related enzyme genes in " Huajin 6" leads to the blockage of JA synthesis, which causes the formation of the long bud phenotype. This study laid a certain foundation for the genetic breeding of Lonicera japonica, provided a new idea for the improvement of Lonicera japonica varieties, and provided a reference for the study of JAs in plant flower organs.

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage(HIBD)and to explore its mechanisms via the PI3K/AKT signaling pathway,aiming to provide a basis for the clinical application of melatonin.Methods Seven-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group,an HIBD group,and a melatonin group(n=9 each).The neonatal rat HIBD model was established using the classic Rice-Vannucci method.Neuronal morphology in the neonatal rat cerebral cortex was observed with hematoxylin-eosin staining and Nissl staining.Autophagy-related protein levels of microtubule-associated protein 1 light chain 3(LC3)and Beclin-1 were detected by immunofluorescence staining and Western blot analysis.Phosphorylated phosphoinositide 3-kinase(p-PI3K)and phosphorylated protein kinase B(p-AKT)protein expression levels were measured by immunohistochemistry and Western blot.The correlation between autophagy and the PI3K pathway in the melatonin group and the HIBD group was analyzed using Pearson correlation analysis.Results Twenty-four hours post-modeling,neurons in the sham operation group displayed normal size and orderly arrangement.In contrast,neurons in the HIBD group showed swelling and disorderly arrangement,while those in the melatonin group had relatively normal morphology and more orderly arrangement.Nissl bodies were normal in the sham operation group but distorted in the HIBD group;however,they remained relatively intact in the melatonin group.The average fluorescence intensity of LC3 and Beclin-1 was higher in the HIBD group compared to the sham operation group,but was reduced in the melatonin group compared to the HIBD group(P<0.05).The number of p-PI3K+and p-AKT+cells decreased in the HIBD group compared to the sham operation group but increased in the melatonin group compared to the HIBD group(P<0.05).LC3 and Beclin-1 protein expression levels were higher,and p-PI3K and p-AKT levels were lower in the HIBD group compared to the sham operation group(P<0.05);however,in the melatonin group,LC3 and Beclin-1 levels decreased,and p-PI3K and p-AKT increased compared to the HIBD group(P<0.05).The correlation analysis results showed that the difference of the mean fluorescence intensity of LC3 and Beclin-1 protein in the injured cerebral cortex between the melatonin and HIBD groups was negatively correlated with the difference of the number of p-PI3K+and p-AKT+cells between the two groups(P<0.05).Conclusions Melatonin can inhibit excessive autophagy in cortical neurons of neonatal rats with HIBD,thereby alleviating HIBD.This mechanism is associated with the PI3K/AKT pathway.

Humans ; Gemcitabine ; Neoplasms

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: To observe the expansion rule of directional skin and soft tissue expander (hereinafter referred to as expander) in abdominal scar reconstruction. Methods: A prospective self-controlled study was conducted. Twenty patients with abdominal scar who met the inclusion criteria and admitted to Zhengzhou First People's Hospital from January 2018 to December 2020 were selected by random number table method, including 5 males and 15 females, aged 12-51 (31±12) years, with 12 patients of type Ⅰ scar and 8 patients of type Ⅱ scar. In the first stage, two or three expanders with rated capacity of 300-600 mL were placed on both sides of the scar, of which at least one expander had rated capacity of 500 mL (as the follow-up observation object). After the sutures were removed, water injection treatment was started, with the expansion time of 4 to 6 months. After the water injection volume reached 2.0 times of the rated capacity of expander, abdominal scar excision+expander removal+local expanded flap transfer repair was performed in the second stage. The skin surface area at the expansion site was measured respectively when the water injection volume reached 1.0, 1.2, 1.5, 1.8, and 2.0 times of the rated capacity of expander, and the skin expansion rate of the expansion site at corresponding multiples of expansion (1.0, 1.2, 1.5, 1.8, and 2.0 times) and adjacent multiple intervals (1.0-1.2, 1.2-1.5, 1.5-1.8, and 1.8-2.0 times) were calculated. The skin surface area of the repaired site at 0 (immediately), 1, 2, 3, 4, 5, and 6 months after operation, and the skin shrinkage rate of the repaired site at different time points (1, 2, 3, 4, 5, and 6 months after operation) and different time periods (0-1, 1-2, 2-3, 3-4, 4-5, and 5-6 months after operation) were calculated. Data were statistically analyzed with analysis of variance for repeated measurement and least significant difference-t test. Results: Compared with the expansion of 1.0 time ((287.6±2.2) cm² and (47.0±0.7)%), the skin surface area and expansion rate of the expansion site of patients ((315.8±2.1), (356.1±2.8), (384.9±1.6), and (386.2±1.5) cm², (51.7±0.6)%, (57.2±0.6)%, (60.4±0.6)%, and (60.5±0.6)%) were significantly increased when the expansion reached 1.2, 1.5, 1.8, and 2.0 times (with t values of 46.04, 90.38, 150.14, 159.55, 45.11, 87.83, 135.82, and 118.48, respectively, P<0.05). Compared with the expansion of 1.2 times, the skin surface area and expansion rate of the expansion site of patients were significantly increased when the expansion reached 1.5, 1.8, and 2.0 times (with t values of 49.82, 109.64, 122.14, 144.19, 49.51, and 105.85, respectively, P<0.05). Compared with the expansion of 1.5 times, the skin surface area and expansion rate of the expansion site of patients were significantly increased when the expansion reached 1.8 times (with t values of 38.93 and 39.22, respectively, P<0.05) and 2.0 times (with t values of 38.37 and 38.78, respectively, P<0.05). Compared with the expansion of 1.8 times, the skin surface area and expansion rate of the expansion site of patients both had no statistically significant differences when the expansion reached 2.0 times (with t values of 4.71 and 4.72, respectively, P>0.05). Compared with the expansion of 1.0-1.2 times, the skin expansion rate of the expansion site of patient was significantly increased when the expansion reached 1.2-1.5 times (t=6.95, P<0.05), while the skin expansion rate of the expansion site of patient was significantly decreased when the expansion reached 1.5-1.8 and 1.8-2.0 times (with t values of 5.89 and 40.75, respectively, P<0.05). Compared with the expansion of 1.2-1.5 times, the skin expansion rate of the expansion site of patient was significantly decreased when the expansion reached 1.5-1.8 and 1.8-2.0 times (with t values of 10.50 and 41.92, respectively, P<0.05). Compared with the expansion of 1.5-1.8 times, the skin expansion rate of the expansion site of patient was significantly decreased when the expansion reached 1.8-2.0 times (t=32.60, P<0.05). Compared with 0 month after operation, the skin surface area of the repaired site of patient at 1, 2, 3, 4, 5, and 6 months after operation was significantly decreased (with t values of 61.66, 82.70, 96.44, 102.81, 104.51, and 102.21, respectively, P<0.05). Compared with 1 month after operation, the skin surface area of the repaired site of patient was significantly decreased at 2, 3, 4, 5, and 6 months after operation (with t values of 37.37, 64.64, 69.40, 72.46, and 72.62, respectively, P<0.05), while the skin shrinkage rate was significantly increased (with t values of 32.29, 50.00, 52.67, 54.76, and 54.62, respectively, P<0.05). Compared with 2 months after operation, the skin surface area of the repaired site of patient was significantly decreased at 3, 4, 5, and 6 months after operation (with t values of 52.41, 60.41, 70.30, and 65.32, respectively, P<0.05), while the skin shrinkage rate was significantly increased (with t values of 52.97, 59.29, 69.68, and 64.50, respectively, P<0.05). Compared with 3 months after operation, the skin surface area of the repaired site of patient was significantly decreased at 4, 5, and 6 months after operation (with t values of 5.53, 38.00, and 38.52, respectively, P<0.05), while the skin shrinkage rate was significantly increased (with t values of 25.36, 38.59, and 37.47, respectively, P<0.05). Compared with 4 months after operation, the skin surface area (with t values of 41.10 and 50.50, respectively, P>0.05) and skin shrinkage rate (with t values of 48.09 and 50.00, respectively, P>0.05) of the repaired site of patients at 5 and 6 months after operation showed no statistically significant differences. Compared with 5 months after operation, the skin surface area and skin shrinkage rate of the repaired site of patient at 6 months after operation showed no statistically significant differences (with t values of 9.40 and 9.59, respectively, P>0.05). Compared with 0-1 month after operation, the skin shrinkage rate of the repaired site of patient at 1-2, 2-3, 3-4, 4-5, and 5-6 months after operation was significantly decreased (with t values of 13.56, 40.00, 49.21, 53.97, and 57.68, respectively, P<0.05). Compared with 1-2 months after operation, the skin shrinkage rate of the repaired site of patients at 2-3, 3-4, 4-5, and 5-6 months after operation was significantly decreased (with t values of 12.37, 27.72, 30.16, and 31.67, respectively, P<0.05). Compared with 2-3 months after operation, the skin shrinkage rate of the repaired site of patients at 3-4, 4-5, and 5-6 months after operation was significantly decreased (with t values of 33.73, 41.31, and 54.10, respectively, P<0.05). Compared with 3-4 months after operation, the skin shrinkage rate of the repaired site of patient at 4-5 and 5-6 months after operation showed no statistically significant differences (with t values of 10.90 and 23.60, respectively, P>0.05). Compared with 4-5 months after operation, the skin shrinkage rate of the repaired site of patient at 5-6 months after operation showed no statistically significant difference (t=20.90, P>0.05). Conclusions: The expander can effectively expand the abdominal skin, thus repairing the abdominal scar deformity. Maintained expansion for one month after the water injection expansion reaches 1.8 times of the rated capacity of the expander can be set as a phase Ⅱ operation node.
Female ; Male ; Humans ; Cicatrix/surgery* ; Prospective Studies ; Tissue Expansion Devices ; Skin ; Abdominal Wall

Objective To observe the effect of polyinosinic-polycytidylic acid ( Poly-IC ) treatment on the expressions of Bcl-2 and Bax after cerebral ischemia-reperfusion ( I / R ) injury in fryperlipidemia rats, and to detect the cerebral infarction, blood-brain barrier permeability and behavioral injury symptoms, to explore the neuroprotective effect of Poly-IC treatment on cerebral I /R injury in fryperlipidemia rats. Methods Hyperlipidemia rats were randomly divided into cerebral I /R group, Poly-IC pretreatment group, Poly-IC post-treatment group and sham operation group, 20 rats in each group. Neurobehavioral performance of rats in each group was recorded according to neurobehavioral score of 0-4 points. Blood-brain barrier permeability of rats in each group was detected by Evans blue staining. TTC staining was used to observe the cerebral infarction in each group. Apoptotic cells in the cerebral cortex of rats in each group was observed by TUNEL staining. The relative expression levels of Bcl-2 and Bax were determined by Western blotting. Results Compared with the sham group, the symptoms of neurobehavioral damage in the I/R group were serious and the score increased significantly (P<0. 05). The scores of Poly-IC pretreatment and post-treatment groups were significantly lower than that of I/R group (P<0. 05). Evans blue staining result showed that the blood-brain barrier permeability of the I/R group was significantly higher than that of the sham group (P<0. 05) , and Poly-IC pretreatment or post-treatment could significantly reduce the blood-brain barrier permeability ( P < 0. 05 ) . No infarct was observed in the sham group with uniform red staining, while white infarct was observed in the brain tissue of the I/R group. Compared with the I/R group, the volume of infarct in both Poly-IC pretreatment and post-treatment groups reduced significantly (P<0. 05). The apoptosis index in cerebral cortex of rats in I/R group was significantly higher than that in sham group ( P < 0 .05 ) , while the apoptosis index in Poly-IC pretreatment or post-treatment group was significantly lower than that in I/R group(P<0. 05 ) . The result of Western blotting showed that, compared with the sham group, the expression of Bax in the I/R group was significantly increased(P<0. 05) , the expression of Bcl-2 was significantly decreased(P<0. 05). Compared with the I/R group, the expression of Bax in the Poly-IC pretreatment or post-treatment group reduced significantly ( P < 0. 05 ) , the expression of Bcl-2 increased significantly(P<0. 05). Conclusion Poly-IC pretreatment or post-treatment can improve the symptoms of neurobehavioral injury, reduce the damage of blood-brain barrier, reduce the volume of cerebral infarction, decrease the apoptosis index of nerve cells, play a neuroprotective effect on cerebral ischemia reperfusion injury in rats with hyperlipidemia, and this protective effect may be related to the change of Bcl-2 and Bax expression levels.

Objective To detecte the expressions of phosphorylated p38 MAPK (p-p38 MAPK), Bax and Bcl-2 in the cerebral cortex of hyperlipidemia rats after cerebral ischemia-reperfusion (I/R) injury and the effect of SB203580 on the expressions of p-p38 MAPK, Bax and Bcl-2, to explore the effect of p38 MAPK activation on the expressions of Bax and Bcl-2 in hyperlipidemia cerebral I/R injury. Methods After the hyperlipidemia model was established, the rats were randomly divided into 3 groups: sham operation group, operation group (I/R) and SB203580 treatment group (SB+I/R), with 10 rats in each group. The focal cerebral I/R model in hyperlipemia rats was established with thread embolism of the left middle cerebral artery. The neurobehavioral score was used to observe the symptoms of neurobehavioral injury. The 2, 3, 5-triphenyltetrazolium chloride (TTC) staining was used to detect the volume of cerebral infarction, and the TUNEL staining was used to observe apoptotic cells. The relative expression levels of p-p38 MAPK, Bax and Bcl-2 were analyzed by immunohistochemistry. Results Compared with the sham group, the infarct volume, apoptosis index and neurobehavioral score of rats in the I/R group increased significantly, and the expressions of p-p38 MAPK and Bax increased significantly, and the expression of Bcl-2 decreased significantly (P<0. 05). Compared with the I/R group, rats in the SB+I/R group had less brain damage, the infarct volume and the apoptosis index were significantly reduced, the expressions of p-p38 MAPK reduced significantly, Bax expression decreased while Bcl-2 expression increased. The differences were statistically significant (P<0. 05). Neurobehavioral scores were lower in SB+I/R group than in I/R group, but the difference was not statistically significant. Conclusion In the process of cerebral I/R injury in hyperlipidemiarats, activation of p38 MAPK can regulate the expression of Bax and Bcl-2.