1. Role of SIRTl/Nrf2/HO-l pathway in attenuation of learning and memory impairment by sevoflurane postcondition in a mouse model of hemorrhagic shock and resuscitation
Zhi-Lun NIU ; Li ZHANG ; Su HU ; Yu-Jie WU ; Xiao-Jing WAN ; Xian-Wen HU
Chinese Pharmacological Bulletin 2024;40(3):551-556
Aim To explore the role of SIRT1/Nrf2 / HO-1 in alleviating the cognitive function impairment by sevoflurane treatment in a mouse model of postoperative cerebral reperfusion. Methods C57BL/6J mice were randomly divided into five groups: sham operation group, hemorrhagic shock reperfusion group, sevoflurane postconditioning group, sevoflurane postcondition-ing + SIRT1 inhibitor group and sevoflurane postconditioning + Nrf2 inhibitor group. Mice were subjected to Morris water maze test after cerebral ischemia reperfusion. The ATP, superoxide dismutase (SOD), ROS and MDA contents in tissue of mice were detected. SIRT1, Nrf2 and HO-1 proteins in tissue were detected by Western blot. Results After hemorrhagic shock, the learning and memory ability of mice was reduced.ATP and SOD concentration in hippocampus was reduced , MDA and ROS concentration increased, and the SIRT, Nrf2 and HO-1 concentration was reduced. Sevoflurane improved the cognitive dysfunction and oxi-dative damage in postoperative mice, and the neuro-protective effect of sevoflurane on hemorrhagic shock and resuscitation mice was weakened followed with SIRT1 and Nrf2 inhibitors. Conclusion Sevoflurane probably alleviates the oxidative reaction damage and cognitive impairment caused by cerebral reperfusion in mice through SIRT1/Nrf2/H0-1 pathway.
2.Efficacy of roxallistat combined with polysaccharide iron complex and Shengxuening in the treatment of maintenance hemodialysis renal anemia with poor recombinant human erythropoietin
Rui-Feng CHEN ; Pei YU ; Zhi-Ting WANG ; Yan LI ; Rui-Xian ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(12):1704-1708
Objective To investigate the efficacy of roxallistat combined with polysaccharide iron complex and Shengxuening in the treatment of maintenance hemodialysis renal anemia with poor recombinant human erythropoiesis.Methods Maintenance hemodialysis renal anemia patients with poor recombinant human erythropoietin effect were divided into control group and treatment group according to random number table method.The control group took roxallistat orally with a body weight of>60 kg,120 mg each time,3 times a week,and 45-60 kg with 100 mg each time,3 times a week;oral polysaccharide iron complex,300 mg each time,once a day.The treatment group was given Shengxuening orally based on the control group,0.25-0.50 g each time,3 times a day.Both groups were treated for 3 months.The clinical efficacy,inflammatory factors,iron metabolism,renal function,anemia index,traditional Chinese medicine symptom score and adverse drug reaction were compared between the two groups.Results In the control group,34 cases were enrolled,1 case fell off,and finally 33 cases were included in the analysis.In the treatment group,35 cases were enrolled,1 case was shed,and 34 cases were finally included in the analysis.After treatment,the total effective rate of treatment group and control group was 97.06%(33 cases/34 cases)and 81.82%(27 cases/33 cases),respectively,and the difference was statistically significant(P<0.05).After treatment,the nuclear transcription factor kappa B(NK-κB)in treatment group and control group were(24.09±3.06)and(35.23±4.11)ng·L-1;interferon gamma(IFN-γ)were(41.39±4.13)and(50.10±5.27)ng·L-1;transferrin saturation(TAST)were(38.62±5.91)%and(31.16±4.73)%;serum ferritin(SF)were(28.13±5.77)and(22.47±4.65)μmol·L-1;serum iron(SI)were(15.66±3.76)and(13.19±2.94)μmol·L-1;urinary protein excretion rate(24 h UPE)were(1.85±0.41)and(2.91±0.62)g·24 h-1;blood urea nitrogen(BUN)were(5.16±0.67)and(6.89±0.97)mmol·L-1;hemoglobin(Hb)were(91.38±11.23)and(83.19±8.54)g·L-1;hematocrit(Hct)were(29.01±7.40)%and(24.56±5.69)%;main disease score were(5.29±1.05)and(7.15±1.53)scores;the secondary scores were(3.11±0.46)and(4.98±0.77)scores;the total scores were(8.40±1.49)and(12.13±2.30)scores,with statistical significance(all P<0.05).The total incidence of adverse drug reactions in treatment group and control group were 14.71%and 9.09%,with no statistical significance(P>0.05).Conclusion Roxallistat combined with polysaccharide and iron complex and Shengxuening have good therapeutic effect in the treatment of maintenance hemodialysis renal anemia with poor recombinant human erythropoietin effect;it can reduce inflammation,regulate iron metabolism,improve renal function,and reduce adverse drug reactions.
3.A new cadinane-type sesquiterpenoid and a new natural product from the aerial parts of Pogostemon cablin
Yu-mei FENG ; Jian-xian TANG ; Zhi-yuan LIU ; Rong-tao LI ; Hong-mei LI
Acta Pharmaceutica Sinica 2024;59(8):2295-2299
A new cadinane-type sesquiterpenoid, pogocablene P (
4.Risk factors for bronchopulmonary dysplasia in twin preterm infants:a multicenter study
Yu-Wei FAN ; Yi-Jia ZHANG ; He-Mei WEN ; Hong YAN ; Wei SHEN ; Yue-Qin DING ; Yun-Feng LONG ; Zhi-Gang ZHANG ; Gui-Fang LI ; Hong JIANG ; Hong-Ping RAO ; Jian-Wu QIU ; Xian WEI ; Ya-Yu ZHANG ; Ji-Bin ZENG ; Chang-Liang ZHAO ; Wei-Peng XU ; Fan WANG ; Li YUAN ; Xiu-Fang YANG ; Wei LI ; Ni-Yang LIN ; Qian CHEN ; Chang-Shun XIA ; Xin-Qi ZHONG ; Qi-Liang CUI
Chinese Journal of Contemporary Pediatrics 2024;26(6):611-618
Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.
5.A prospective randomized controlled study on probiotics for the prevention of antibiotic-associated diarrhea in infants and young children
Su-Wei ZHANG ; Xian ZHI ; Meng-Yu WANG ; Dong-Lin SHEN
Chinese Journal of Contemporary Pediatrics 2024;26(10):1108-1114
Objective To evaluate the preventive effects of Saccharomyces boulardii powder and tetragenous viable Bifidobacterium tablets on antibiotic-associated diarrhea(AAD)in infants and young children.Methods Children under three years old admitted to the Department of Pediatrics,Affiliated Hospital of Xuzhou Medical University due to non-gastrointestinal infections and requiring antibiotic treatment from July to December 2023 were enrolled.The children were randomly divided into a control group(n=47),a Saccharomyces boulardii group(n=70),and a Bifidobacterium group(n=65)using a random number table method.The control group received antibiotics and symptomatic supportive treatment according to relevant clinical guidelines.In addition to the treatment given to the control group,the Saccharomyces boulardii group and the Bifidobacterium group were respectively administered with Saccharomyces boulardii powder and tetragenous viable Bifidobacterium tablets.Based on the duration of probiotic use(7 days,14 days,and 21 days),the Saccharomyces boulardii group was further divided into 7 d,14 d,and 21 d subgroups,and similarly for the Bifidobacterium group.The incidence of AAD and ratio of cocci to bacilli in feces were compared among the groups after treatment.Results The incidence rate of AAD in both the Saccharomyces boulardii group and the Bifidobacterium group was lower than that in the control group(P<0.017).The duration of AAD and the length of hospital stay were shorter in the Saccharomyces boulardii and Bifidobacterium groups compared to the control group(P<0.05).In the control group,the ratio of cocci to bacilli in feces on days 7,14,and 21 was higher than on day 1(P<0.05).Within-group comparisons showed that the ratio of cocci to bacilli in feces on day 14 in the Bifidobacterium 14 d and 21 d groups were lower than on day 1(P<0.05);and the ratios on day 14 in the control group,Saccharomyces boulardii 14 d group,Saccharomyces boulardii 21 d group,Bifidobacterium 14 d group,and Bifidobacterium 21 d group were lower than on day 7(P<0.05).The ratios on day 21 in the control group and the Saccharomyces boulardii 21 d group were lower than on days 7 and 14(P<0.05).Between-group comparisons indicated that on day 7,the ratios of cocci to bacilli in feces in the Saccharomyces boulardii 7 d,14 d,21 d groups,and Bifidobacterium 7 d,14 d,21 d groups were all lower than in the control group(P<0.05);on day 14,the ratios of cocci to bacilli in feces 14 d and 21 d groups were lower than in the control group and the Bifidobacterium 7 d group(P<0.05).Conclusions Both Saccharomyces boulardii and tetragenous viable Bifidobacterium can effectively improve gut microbiota and prevent the occurrence of AAD in infants and young children.Compared to short-term treatment,appropriately extending the duration of probiotic therapy can further improve the structure of gut microbiota.
6.Recurrent spinal subdural hematoma following percutaneous kyphoplasty: A unique case report
Wen-Hui LIU ; Xin-Min LIN ; Xin-Yu LU ; Hai HAN ; Liang-Zhi ZHANG ; Hai-Xian LIN ; Zi-Wen LIU
Chinese Journal of Traumatology 2024;27(6):354-358
Spinal intradural (subdural and subarachnoid) hematoma following percutaneous kyphoplasty is an extremely rare complication. In this report, we described a case of 2 episodes of subarachnoid hemorrhage with delayed paralysis after kyphoplasty. A 73-year-old man underwent percutaneous kyphoplasty in our hospital an osteoporotic vertebral fracture at the T12 level. On the 55 h after kyphoplasty for T12 osteoporotic vertebral fracture, he developed paralysis of the lower limbs. An emergency posterior decompression from T8 to L2 was performed. And the subarachnoid hematomas were removed. Postoperatively, the neurological symptoms improved rapidly. However, 2 weeks after the operation, the patient experienced a setback with severe neurological decline (paraplegia with sensory and autonomic dysfunction). An emergency posterior decompression from T5 to L2 was performed. The subarachnoid hematomas were removed. This case reflects the cause and progression of spinal subdural hematoma. Previous literature has debated the best treatment approach for spinal subarachnoid hemorrhage, but the prognosis of patients is heavily dependent on precise symptom evaluation and localization.
7.Treadmill Exercise Improves Cognitive Dysfunction in Diabetic Mice by Regulating PANoptosis Through the p38 MAPK Signaling Pathway
Ke-Yan SHENG ; Yu-Yan CHEN ; Yuan GAO ; Bao-Wen ZHANG ; Meng ZHANG ; Zhi WANG ; Xian-Juan KOU
Chinese Journal of Biochemistry and Molecular Biology 2024;40(7):987-998
Cognitive dysfunction is one of the serious complications of type 2 diabetes.Exercise interven-tion has a certain effect on improving diabetes cognition,but the exact process remains ambiguous.This research aims to explore the impact and molecular processes of treadmill exercises in enhancing cognitive impairments in type 2 diabetic mice.Ten m/m 8-week-old male mice were used as the control group.Forty db/db mice,each 8 weeks old and male,were categorized into four distinct groups with each group containing 10 mice,including the db/db group(model group),db+Exe group(exercise group),db+Exe+SB203580 group(exercise combined with the p38 MAPK inhibitor group),db+SB203580 group(p38 MAPK inhibitor group).db+Exe group and db+Exe+SB203580 group were subjected to treadmill running intervention(40 min/time,5 times/week,a total of 8 weeks).db+Exe+SB203580 and db+SB203580 group were intraperitoneally injected with SB203580(5 mg/kg,5 times/week,8 weeks)2 hours before treadmill exercise.The results of body weights and fasting blood glucose measurement showed that 8-week treadmill exercise could significantly reduce the body mass and fasting blood glucose levels(P<0.01);the results of water maze showed that treadmill exercise improved cognitive dysfunction in diabetic mice(P<0.05).Immunofluorescence staining revealed that treadmill exercise diminished the fluorescence intensity of NLRP3 in hippocampus,and there was a significant difference in CA1 and CA3 regions(P<0.05).Treadmill exercise reduced the fluorescence intensity of PI in the hippocampus,and there was a significant difference in the DG region(P<0.01).The results of qRT-PCR revealed that treadmill exercise decreased IL-1β and IL-18 mRNA levels in hippocampus,with a notable difference in IL-1β mRNA levels(P<0.05).Western blotting analysis revealed that treadmill exercise reduced the concentrations of Caspase3,Caspase9 and Bax in hippocampus(P<0.01),reduced the concentrations of TXNIP,NLRP3,GSDMD-N,IL-1β,IL-18,Cleaved Caspase1 and Caspasel(P<0.05),decreased the levels of p-RIPK1,RIPK1,p-RIPK3 and RIPK3(P<0.05).After adding p38 inhibitors,treadmill ex-ercise combined with p38 inhibitor intervention further inhibited the expression of Caspase3,TXNIP,GS-DMD-N and IL-18(P<0.05),and the expression levels of Caspase9,Bax,NLRP3,IL-1β,Cleaved Caspase 1 and Caspase 1 also showed a downward trend.The expression of RIPK1 and p-RIPK3 in-creased significantly(P<0.05),and the protein expression levels of p-p38,p-RIPK1 and RIPK3 showed an upward trend.In conclusion,treadmill running intervention can effectively improve the cogni-tive dysfunction in type 2 diabetic mice,and its mechanism is partly through the p38 MAPK signaling pathway to regulate PANoptosis.
8.The Effect of SIRT5 Deletion on Recovery of Hematopoietic Stem Cells after Injury in Mouse
Yuan-Yao DENG ; Han-Chuan MOU ; Xian ZHANG ; Fan REN ; Zhi-Yang CHEN ; Zhen-Yu JU ; Hui-Ling LOU
Journal of Experimental Hematology 2024;32(2):568-576
Objective:To investigate the effect of deacylase Sirtuin 5 in the recovery of hematopoietic stem cells(HSCs)after treated by 5-FU in mouse.Methods:Flow cytometry was used to analyze the effect of SIRT5 deletion on the proportion of hematopoietic stem/progenitor cells(HSPCs)in bone marrow(BM),the proportion of T cells,B cells and myeloid cells(TBM)in peripheral blood(PB)and spleen,and the development of T cells in thymus.Mouse were treated with 5-FU to study the effect of SIRT5 deletion on the cell cycle,apoptosis and the proportion of HSPCs in BM.The effect of SIRT5 deletion on the proliferation of HSCs was analyzed by flow sorting in vitro.Results:SIRT5 deletion did not affect the development of T cells in thymus and the proportion of TBM cells in PB and spleen compared with wild type mice.SIRT5 deletion increased proportion of HSPCs in BM.After 5-FU treatment,the proportion of HSCs in SIRT5 deletion mice was significant decreased(P<0.05),the HSPC in SIRT5 deletion mice was activated from G0 to G1 phase(P<0.05),and the proportion of early apoptosis increased(P<0.05).By monoclonal culture in vitro,the ability of HSCs to form clones in SIRT5 deletion mice was decreased significantly(P<0.05).Conclusion:SIRT5 deletion lead to a decreased the ability of HSCs to clone in vitro.SIRT5 deletion is not conducive to the recovery of HSPCs injury in mice under hematopoietic stress.
9.Gene Analysis of Combined Dual Rare Thalassemia
Cheng-De LI ; Guang-Yu XIAN ; Xiao-Jia HUANG ; Shan CHEN ; Li-Xia LIANG ; Zhi-Fang LIN
Journal of Experimental Hematology 2024;32(5):1479-1484
Objective:To retrospectively analyze the detection and diagnosis process of two cases with double rare thalassemia genotypes,explore the causes of missed diagnosis and misdiagnosis of rare thalassemia,and improve the diagnosis level of rare thalassemia.Methods:Base on the family history,hematological phenotype and hemoglobin electrophoretic analysis results,the common genotypes of α and β-thalassemia were detected by PCR+diversion hybridization.DNA sequencing technology was used for rare α and β protein genes sequencing.Results:Both subjects were combined with double rare thalassemia genotypes,and both rare thalassemia gene combinations were reported for the first time.One of them was αβ complex thalassemia with αα*53_55 del TCC/αα heterozygous merger βIVS Ⅱ2(-T)/βN heterozygous,the other was ααIVS-Ⅱ-55(T→G)in α1/αα4,2-Q double azygous heterozygous α-thalassemia,among whichαα*53_55 del TCC/αα genotype was also reported for the first time.Conclusion:The reported rare gene type αα*53_55 del TCC/αα and two cases of rare gene combinations enriches the spectrum of gene mutations in the Chinese population,and provides richer molecular information for thalassemia diagnosis and eugenics counseling.
10.Preliminary study on delaying aging induced thymus degeneration in SAMP6 mice with Bazi Bushen capsule
Zhao-Dong LI ; Yin-Xiao CHEN ; Bo-Yang GONG ; Zhe XU ; Zhi-Xian YU ; Yue-Xuan SHI ; Yan-Fei PENG ; Yu-Hong BIAN ; Yun-Long HOU ; Xiang-Ling WANG ; Shu-Wu ZHAO
Chinese Pharmacological Bulletin 2024;40(6):1186-1192
Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P<0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P<0.01);the proportion of CD3+T cells apparently increased(P<0.05);the level of p16 protein signifi-cantly decreased(P<0.05);the level of Bcl-2 pro-tein significantly increased(P<0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P<0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P<0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.

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