Serine protease 50(PRSS50/TSP50)is highly expressed in spermatocytes.Our study investigated its role in testicular development and spermatogenesis.Initially,PRSS50 knockdown was observed to impair DNA synthesis in spe...Serine protease 50(PRSS50/TSP50)is highly expressed in spermatocytes.Our study investigated its role in testicular development and spermatogenesis.Initially,PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes.To further explore this,we generated PRSS50 knockout(Prss50^(−/−))mice(Mus musculus),which exhibited abnormal spermatid nuclear compression and reduced male fertility.Furthermore,dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50^(−/−)mice,accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells.Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2(ERK1/2)and elevated levels of MAP kinase phosphatase 3(MKP3),a specific ERK antagonist,potentially accounting for testicular dysplasia in adolescent Prss50−/−mice.Taken together,these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis,with the MKP3/ERK signaling pathway playing a significant role in this process.展开更多
Boreal forests commonly suff er from nitrogen defi ciency due to low rate of nitrogen mineralization.Biochar may promote soil organic matter decomposition and accelerate nitrogen mineralization.In this study,Illumina ...Boreal forests commonly suff er from nitrogen defi ciency due to low rate of nitrogen mineralization.Biochar may promote soil organic matter decomposition and accelerate nitrogen mineralization.In this study,Illumina NovaSeq sequencing combined with functional annotation of prokaryotic taxa(FAPROTAX)analysis was used to investigate the eff ect of biochar pyrolysis temperatures,the amount of applied biochar,and the period since the biochar application(2-and 3-year)on soil bacterial communities.The results show that biochar pyrolysis temperatures(500℃ and 650℃)and the amount of applied biochar(0.5 kg m^(−2)and 1.0 kg m^(−2))did not change soil properties.Nevertheless,the interaction of biochar pyrolysis temperature and the amount had signifi cant eff ects on bacterial species richness and evenness(P<0.05).The application of biochar produced at 500℃ had a lower abundance of Actinobacteria and Verrucomicrobia,while that produced at 650℃ had a higher abundance of Conexibacter and Phenylobacterium.When biochar produced at 650℃ was applied,applying 0.5 kg m^(−2)had a higher abundance of Cyanobacteria,Conexibacter,and Phenylobacterium than that of 1.0 kg m^(−2)(P<0.05).Functionally,the abundance of the aromatic compound degradation group increased with the extension of application time and increase of pyrolysis temperature.The time since application played an important role in the formation of soil bacterial communities and their functional structure.Long-term studies are necessary to understand the consequence of biochar on bacterial communities in boreal forests.展开更多
Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve rep...Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication.Nevertheless,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear.To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation.The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells.We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells.Subsequently,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded miR-21-5p.Finally,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously restored.These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p.miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome.This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves,and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.展开更多
The fermented Chinese formula Shuan-Tong-Ling is composed of radix puerariae(Gegen),salvia miltiorrhiza(Danshen),radix curcuma(Jianghuang),hawthorn(Shanzha),salvia chinensis(Shijianchuan),sinapis alba(Baiji...The fermented Chinese formula Shuan-Tong-Ling is composed of radix puerariae(Gegen),salvia miltiorrhiza(Danshen),radix curcuma(Jianghuang),hawthorn(Shanzha),salvia chinensis(Shijianchuan),sinapis alba(Baijiezi),astragalus(Huangqi),panax japonicas(Zhujieshen),atractylodes macrocephala koidz(Baizhu),radix paeoniae alba(Baishao),bupleurum(Chaihu),chrysanthemum(Juhua),rhizoma cyperi(Xiangfu) and gastrodin(Tianma),whose aqueous extract was fermented with lactobacillus,bacillus aceticus and saccharomycetes.ShuanTong-Ling is a formula used to treat brain diseases including ischemic stroke,migraine,and vascular dementia.Shuan-Tong-Ling attenuated H_2O_2-induced oxidative stress in rat microvascular endothelial cells.However,the potential mechanism involved in these effects is poorly understood.Rats were intragastrically treated with 5.7 or 17.2 m L/kg Shuan-Tong-Ling for 7 days before middle cerebral artery occlusion was induced.The results indicated Shuan-Tong-Ling had a cerebral protective effect by reducing infarct volume and increasing neurological scores.Shuan-Tong-Ling also decreased tumor necrosis factor-α and interleukin-1β levels in the hippocampus on the ischemic side.In addition,Shuan-Tong-Ling upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of acetylated-protein 53 and Bax.Injection of 5 mg/kg silent information regulator 1(SIRT1) inhibitor EX527 into the subarachnoid space once every 2 days,four times,reversed the above changes.These results demonstrate that Shuan-Tong-Ling might benefit cerebral ischemia/reperfusion injury by reducing inflammation and apoptosis through activation of the SIRT1 signaling pathway.展开更多
Background Metabolic syndrome is known to be a prothrombotic state. We undertook this study to examine a hypothesis that aspirin resistance may be associated with metabolic syndrome, and to assess other potential dete...Background Metabolic syndrome is known to be a prothrombotic state. We undertook this study to examine a hypothesis that aspirin resistance may be associated with metabolic syndrome, and to assess other potential determinants of aspirin resistance in patients with cardiovascular disease (CVD). Methods A total of 469 elderly patients with CVD were recruited. One hundred and seventy-two patients with metabolic syndrome and 297 without metabolic syndrome (control group) received daily aspirin therapy (〉 75 mg) over one month. Platelet aggregation was measured by light transmission aggregometry (LTA). Aspirin resistance was defined as 〉 20% arachidonic acid (AA)- and 〉 70% adenosine diphosphate (ADP)-induced aggregation according to LTA. Aspirin semi-responders were defined as meeting one (but not both) of these criteria. Results By LTA, 38 of 469 (8.1%) patients were aspirin resistant. The prevalence of aspirin resistance was higher in the metabolic syndrome group compared with the control group [11.6 % vs. 6.6%, odds ratio (OR) = 2.039; 95% confidence interval (CI): 1.047-3.973]. In the multivariate logistic regression analysis, metabolic syndrome (OR = 4.951, 95% CI: 1.440-17.019, P = 0.011) was a significant risk factor for aspirin resistance. Conclusions A significant number of patients with CVD and metabolic syndrome are resistant to aspirin therapy. This might further increase the risk of cardiovascular morbidity and mortality in these patients.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related deaths worldwide,but there is a shortage of effective biomarkers for its diagnosis.AIM To explore blood exosomal micro ribonucleic...BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related deaths worldwide,but there is a shortage of effective biomarkers for its diagnosis.AIM To explore blood exosomal micro ribonucleic acids(miRNAs)as potential biomarkers for HCC diagnosis.RESULTS The principal component analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of hepatitis B virus positive non-HCC patients through miR-3168 and miR-223-3p.The miRNA profiles also revealed the tumor stages of HCC patients.High expression of miR-455-5p and miR-30c-5p,which significantly correlated with better overall survival in tumor tissues,could also be detected in blood exosomes.Two pairs of miRNAs(miR-584-5p/miR-106-3p and miR-628-3p/miR-941)showed a 94.1%sensitivity and 68.4%specificity to differentiate HCC patients from non-HCC patients.The specificity of the combination was substantially influenced by alcohol consumption habits.CONCLUSION This study suggested that blood exosomal miRNAs can be used as new noninvasive diagnostic tools for HCC.However,their accuracy could be affected by tumor stage and alcohol consumption habits.展开更多
AIM: To investigate the effects of green flickering light on refractive development and expression of muscarinic acetylcholine receptor(mAChR) M1 in the eyes of guinea pigs.METHODS: Thirty guinea pigs(15-20 days ...AIM: To investigate the effects of green flickering light on refractive development and expression of muscarinic acetylcholine receptor(mAChR) M1 in the eyes of guinea pigs.METHODS: Thirty guinea pigs(15-20 days old) were randomly divided into three groups(n=10/group). Animals in group I were raised in a completely closed carton with green flickering light illumination. Those in group II were kept in the open top closed carton under normal natural light. Guinea pigs were raised in a sight-widen cage under normal natural light in group III. The refractive status and axial length were measured before and after 8 weeks' illumination. Moreover, total RNA extracted from retinal, choroidal, and scleral tissues were determined by real-time reverse transcription polymerase chain reaction(RT-PCR). The expressions of the receptor M1 were also explored in the retina, choroid, and sclera using immunohistochemistry.RESULTS: There was a remarkable reduction in refractive error and increase in axial length after 8-weeks' green flickering light stimulation(P〈0.001). The expression of M1 receptor mRNA in sclera and retina in myopia group were remarkably lower than that in group II and III(P〈0.01). Significant reduced expression of M1 receptor stimulated by green flickering light in retina and sclera tissues were also observed(P〈0.05). However, there was no M1 receptor expression in choroid in 3 groups.CONCLUSION: Myopia can be induced by 8 weeks' green flickering light exposure in the animal model. M1 receptor may be involved causally or protectively in myopia development.展开更多
The objective of the present study was to compare the toxicity and availability of Fe(II) and Fe(III) to Caco-2 cells. Cellular damage was studied by measuring cell proliferation and lactate dehydrogenase (LDH) releas...The objective of the present study was to compare the toxicity and availability of Fe(II) and Fe(III) to Caco-2 cells. Cellular damage was studied by measuring cell proliferation and lactate dehydrogenase (LDH) release. The activities of two major antioxidative enzymes [superoxide dismutase (SOD) and glutathione peroxidase (GPx)] and differentiation marker (alkaline phosphatase) were determined after the cells were exposed to different levels of iron salts. The cellular iron concentration was investigated to evaluate iron bioavailability. The results show that iron uptake of the cells treated with Fe(II) is significantly higher than that of the cells treated with Fe(III) (P<0.05). Fe(II) at a concentration >1.5 mmol/L was found to be more effective in reducing cellular viability than Fe(III). LDH release investigation suggests that Fe(II) can reduce stability of the cell membrane. The activities of SOD and GPx of the cells treated with Fe(II) were higher than those of the cells treated with Fe(III), although both of them increased with raising iron supply levels. The results indicate that both Fe(II) and Fe(III) could reduce the cellular antioxidase gene expression at high levels.展开更多
Pyoderma gangrenosum(PG)is an uncommon ulcerative cutaneous condition of an unknown etiology and is often associated with immune diseases.However,PG rarely shows visceral involvement,especially in the kidney.A 20-year...Pyoderma gangrenosum(PG)is an uncommon ulcerative cutaneous condition of an unknown etiology and is often associated with immune diseases.However,PG rarely shows visceral involvement,especially in the kidney.A 20-year-old female presented with pedal edema and skin ulceration of both lower limbs.The skin lesion began as an erythematous plaque and then became a blister.She also complained of abdominal distension and a decreasing urine volume.Laboratory data showed high proteinuria,hypoalbuminemia and hyperlipidemia.Her skin and kidney were biopsied.The pathological results indicated PG and immunoglobulin A(IgA)nephropathy.The patient was finally cured with prednisolone in combination with cyclosporine A(CsA).展开更多
BACKGROUND Craniometaphyseal dysplasia(CMD)is a rare genetic disorder.Autosomal dominant CMD(AD-CMD)is caused by mutations in the ANKH gene.Affected individuals typically have distinctive facial features including pro...BACKGROUND Craniometaphyseal dysplasia(CMD)is a rare genetic disorder.Autosomal dominant CMD(AD-CMD)is caused by mutations in the ANKH gene.Affected individuals typically have distinctive facial features including progressive thickening of the craniofacial bones.Treatment for AD-CMD primarily consists of surgical intervention to release compression of the cranial nerves and the brain stem/spinal cord.To alleviate progression of the clinical course and improve the quality of life in children waiting to undergo the necessary surgery,we investigated clinical changes in a diagnosed patient with AD-CMD over three years.CASE SUMMARY A 17-mo-old boy presented with progressive nasal obstruction,snoring and hearing loss symptoms.Physical examination showed enlargement of the head circumference and clinical features such as wide nasal bridge,paranasal bossing,widely spaced eyes with an increased bizygomatic width,and a prominent mandible.The patient underwent otolaryngological examination,endoscopy,hearing test,laboratory examination of phosphorus and bone metabolism,cranial and femoral computed tomography,X-ray and next-generation sequencing.The patient was diagnosed with AD-CMD due to p.Phe377 deletion(c.1129_1131del)on exon 9 of the ANKH gene.After adherence to a prescribed low-calcium diet,the boy’s alkaline phosphatase(ALP)levels continuously decreased to within the normal range.However,after 14 mo of dietary intervention,his parents altered his diet to an intermittent low-calcium diet to include milk and eggs.The patient’s ALP was slightly higher than normal after the dietary change but remained close to the normal range.His serum osteocalcin changed to within normal levels after dietary regulation for 33 mo.His serum combined beta C-terminal telopeptide of type I collagen also continuously decreased after the nutritional intervention,although still slightly higher than normal levels.Despite fluctuating blood test results,the boy’s nasal symptoms were markedly relieved and steadily improved after dietary intervention.No significant changes were found in the craniofacial bones by cranial radiography.Close monitoring of clinical features is still ongoing.Calcitriol treatment is currently under consideration and a surgical procedure is planned as necessary in the future.CONCLUSION We herein report the first Chinese case of AD-CMD with heterozygous mutation of p.Phe377 deletion(c.1129_1131del)on the ANKH gene.Biochemical alterations were significantly improved after dietary intervention indicating that a lowcalcium diet may be applied in pediatric AD-CMD patients with ANKH mutations to help alleviate phenotypic manifestations and improve the quality of life before surgical intervention.Further large scale studies are needed to replicate these findings and to establish the appropriate timing for nutritional and surgical interventions。展开更多
Objective:To explore the clinical effect of ambroxol hydrochloride combined with rehabilitation training on COPD and its effect on pulmonary function.Methods:92 patients with COPD from May 2017 to may 2019 were random...Objective:To explore the clinical effect of ambroxol hydrochloride combined with rehabilitation training on COPD and its effect on pulmonary function.Methods:92 patients with COPD from May 2017 to may 2019 were randomly divided into control group(n=46)and observation group(n=46).The control group was treated with oxygen inhalation,expectorant,antispasmodic,anti infection and so on.The observation group was treated with ambroxol hydrochloride combined with rehabilitation training on this basis.Blood gas,lung function and inflammatory factors were compared before and after treatment.Results:the levels of SaO2 and PaO2 in the two groups were significantly higher than those before treatment P There was significant difference between the two groups(P<0.05-0.01).Besides,the level of lung function related indexes in the observation group was significantly higher than that in the control group(P<0.05).Conclusion:ambroxol hydrochloride combined with rehabilitation training has a significant clinical effect on COPD,which can effectively improve the blood gas index and reduce the level of blood gas inflammatory factors,thus affecting the lung function of COPD patients.展开更多
BACKGROUND Duodenum-preserving pancreatic head resection(DPPHR)is the choice of surgery for benign or low-grade malignant tumors of the pancreatic head.Laparoscopic DPPHR(LDPPHR)procedure can be improved by preoperati...BACKGROUND Duodenum-preserving pancreatic head resection(DPPHR)is the choice of surgery for benign or low-grade malignant tumors of the pancreatic head.Laparoscopic DPPHR(LDPPHR)procedure can be improved by preoperative 3D model reconstruction and the use of intravenous indocyanine green fluorescent before surgery for real-time navigation with fluorescent display to guide the surgical dissection and prevention of from injury to vessels and biliary tract.CASE SUMMARY Here we report the successful short-and long-term outcomes after one year following LDPPHR for a 60-year lady who had an uneventful recovery and was discharged home one week after the surgery.CONCLUSION There was no bile leakage or pancreatic leakage or delayed gastric emptying.The histopathology report showed multiple cysts in the pancreatic head and localized pancreatic intraepithelial tumor lesions.The resected margin was free of tumor.展开更多
Objective:To observe the protective effect of fasudil hydrochloride against acute renal injury in septicopyemia rats.Methods:A total of 60 Wister rats were included in the study and divided into control group(n = 10),...Objective:To observe the protective effect of fasudil hydrochloride against acute renal injury in septicopyemia rats.Methods:A total of 60 Wister rats were included in the study and divided into control group(n = 10),model group(n = 25) and treatment group(n = 25).Model group and treatment group received intraperitoneal injection of endotoxin(ET) to establish acute renal injury models while the control group only received daily intraperitoneal injection of normal saline 1 mL.Five rats were taken out of model group and treatment group respectively at 1 h(T1),6 h(T2),12 h(T3),24 h(T4) and 48 h(T5),for intraperitoneal injection of ET 30 mg/kg.Treatment group received intraperitoneal injection of fasudil hydrochloride 30 mg/kg 1 h before injection of ET.For three groups,5 mL blood samples were collected from postcava for determination of serum creatinine and urea nitrogen levels at different time points.Concentrations of serum tumor necrosis factor and ET-1 were determined by using ELISA.The renal pathologic changes were observed under the microscope.Results:Serum creatinine levels in both model group and treatment group were significantly higher than control group at T2-T5(P < 0.05) while the levels in treatment group were significantly lower than control group at T3-T5(P < 0.05).At T2-T5,blood urea nitrogen levels in model group and treatment group were significantly higher than control group(P < 0.05) while the levels in treatment group were significantly lower than model group at T3-T5(P < 0.05).Concentrations of serum tumor necrosis factor in model group and treatment group were significantly higher than control group at T1-T5(P < 0.05) while the levels in treatment group were significantly lower than model group at T1-T5(P < 0.05).Serum ET-1 concentrations in model group and treatment group were significantly higher than control group at T1-T5(P <0.05) while the levels in treatment group at T1-T4 were significantly lower man model group(P <0.05).Rats in control group showed no swelling or hyperaemia in kidney cells but normal structure and normally arranged renal tubular epithelial cells.Obvious injury was observed in model group at T3 and renal tubular epithelial cells in disorder and at swelling condition,hyperaemia and angiectasis in glomerulus,degenerative opacities and vacuolar degeneration,and maximized injury were observed at T4.Injury in renal tissue in treatment group was significantly milder than model group.Conclusions:Fasudil hydrochloride has the significantly protective effect against acute renal injury in septicopyemia rats.展开更多
Phytochemical investigation of the aerial parts of Euphorbia sikkimensis led to the isolation of one new diterpenoids,named sikkimenoid E(1),together with thirteen other known compounds(2-14).Their structures were est...Phytochemical investigation of the aerial parts of Euphorbia sikkimensis led to the isolation of one new diterpenoids,named sikkimenoid E(1),together with thirteen other known compounds(2-14).Their structures were established by means of spectroscopic methods.Compound 2 was identified to be a trinortriterpenoid,and derived for the first time from a natural source.In this paper we reveal for the first time its comprehensive spectral data and NMR spectral assignment.Compound 4 showed anti-angiogenic activity with an IC_(50) value of 5.66μM in a zebrafish model,and compounds 5 and 6 exhibited cytotoxicity toward A549 cell line with IC_(50) values of 12.12 and 6.45μM,respectively.展开更多
Two new minor constituents,musinisins A(1)and B(2),together with five known compounds(3-7),were isolated from the aerial parts of Munronia sinica.Their structures were established by means of spectroscopic methods and...Two new minor constituents,musinisins A(1)and B(2),together with five known compounds(3-7),were isolated from the aerial parts of Munronia sinica.Their structures were established by means of spectroscopic methods and the absolute stereochemistry of 1 was determined by single crystal X-ray experiment.Compound 4 showed antiangiogenic activity evaluated by a zebrafish model and apoptosis-inducing effect on A549 lung cancer cells.展开更多
BACKGROUND:Blood hemoperfusion with resin adsorption can clean larger molecules that exceed the molecular weight cutoff of combined continuous veno-venous hemofiltration(CWH).Hence blood hemoperfusion with resin adsor...BACKGROUND:Blood hemoperfusion with resin adsorption can clean larger molecules that exceed the molecular weight cutoff of combined continuous veno-venous hemofiltration(CWH).Hence blood hemoperfusion with resin adsorption combined CWH(HP+CWH) has higher ability of mediator clearance,and can improve clinical outcomes in theory.This study aimed to investigate the effect of blood hemoperfusion with resin adsorption combined continuous veno-venous hemofiltration(HP+CWH) on plasm cytokines like TNF-α,IL-1β,IL-6,cellular immunity and prognosis in patients with multiple organ dysfunction syndrome(MODS).METHODS:This was a prospective,randomized clinical trial.A total of 30 patients who had been diagnosed with MODS were enrolled in this study.Patients were randomly allocated to routine treatment+HP+CWH group(treatment group) and routine treatment+only CWH group(control group).In the treatment group,patients received blood hemoperfusion with resin adsorption for 2hours,and then received CWH for 10 hours every day.In the control group,patients received CWH for 12 hours only every day.The patients in the two groups received blood purification therapy for three days.The plasma of patients in the treatment group was obtained at 0,2,12,24,26,36,48,50,60 hours,5th day,7th day and 10 th day,respectively.The plasma of patients in the control group was obtained at 0,12,24,36,48,60 hours,5th day,7th day and 10 th day,respectively.APACHE Ⅱscore,T-lymphocytes subpopulations,blood lactate acid concentration,heart rate,breathing rate,and oxygenation index were observed.RESULTS:Plasma cytokines like TNF-α,IL-1β,IL-6 decreased markedly after HP(P<0.01);T-lymphocytes subpopulations CD3+,CD4+,CD8+,CD4+/CD8+ increased after HP+CWH or only CWH.The plasma concentrations of TNF-α,IL-1β and IL-6 in the two groups were not markedly different at 12,36,and 50 hours.But on the 5th day,the plasma concentrations of TNF-α,IL-1β and IL-6 in the treatment group were lower than those in the control group(P<0.05).On the 28 th day,5patients died in the treatment group,and 6 patients in the control group.CONCLUSIONS:Both HP+CWH and CWH can clean plasma cytokines like TNF-α,IL-1β,and IL-6,and improve cellular immunity and clinical symptoms and signs of patients.Compared with only CWH,the plasma concentrations of TNF-α,IL-1β and IL-6 were lower on the 5th day,and patients have an increased survival rate on the 28 day in the HP+CWH group.展开更多
基金supported by the Research Foundation of Jilin Provincial Science&Technology Development(20210204164YY,YDZJ202201ZYTS524,20230204067YY,20230204069YY)Jilin Province Development and Reform Commission(2022C044-3)Fundamental Research Funds for the Central Universities(135131002)。
文摘Serine protease 50(PRSS50/TSP50)is highly expressed in spermatocytes.Our study investigated its role in testicular development and spermatogenesis.Initially,PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes.To further explore this,we generated PRSS50 knockout(Prss50^(−/−))mice(Mus musculus),which exhibited abnormal spermatid nuclear compression and reduced male fertility.Furthermore,dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50^(−/−)mice,accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells.Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2(ERK1/2)and elevated levels of MAP kinase phosphatase 3(MKP3),a specific ERK antagonist,potentially accounting for testicular dysplasia in adolescent Prss50−/−mice.Taken together,these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis,with the MKP3/ERK signaling pathway playing a significant role in this process.
基金funded by The Foundation for Research of Natural Resources in Finland(2016085)supported by the Academy of Finland(286685,294600,307222,277623)the FCoE of atmospheric sciences(Center of Excellence(1118615)).
文摘Boreal forests commonly suff er from nitrogen defi ciency due to low rate of nitrogen mineralization.Biochar may promote soil organic matter decomposition and accelerate nitrogen mineralization.In this study,Illumina NovaSeq sequencing combined with functional annotation of prokaryotic taxa(FAPROTAX)analysis was used to investigate the eff ect of biochar pyrolysis temperatures,the amount of applied biochar,and the period since the biochar application(2-and 3-year)on soil bacterial communities.The results show that biochar pyrolysis temperatures(500℃ and 650℃)and the amount of applied biochar(0.5 kg m^(−2)and 1.0 kg m^(−2))did not change soil properties.Nevertheless,the interaction of biochar pyrolysis temperature and the amount had signifi cant eff ects on bacterial species richness and evenness(P<0.05).The application of biochar produced at 500℃ had a lower abundance of Actinobacteria and Verrucomicrobia,while that produced at 650℃ had a higher abundance of Conexibacter and Phenylobacterium.When biochar produced at 650℃ was applied,applying 0.5 kg m^(−2)had a higher abundance of Cyanobacteria,Conexibacter,and Phenylobacterium than that of 1.0 kg m^(−2)(P<0.05).Functionally,the abundance of the aromatic compound degradation group increased with the extension of application time and increase of pyrolysis temperature.The time since application played an important role in the formation of soil bacterial communities and their functional structure.Long-term studies are necessary to understand the consequence of biochar on bacterial communities in boreal forests.
基金supported by the National Natural Science Foundation of China,No.31870977(to HYS)the National Key Technologies Research and Development Program of China,No.2017YFA0104700(to FD)+2 种基金2022 Jiangsu Funding Program for Excellent Postdoctoral Talent(to MC)Priority Academic Program Development of Jiangsu Higher Education Institutions[PAPD]the Major Project of Basic Science(Natural Science)Research in Higher Education Institutions of Jiangsu Province,No.22KJA180001(to QRH)。
文摘Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication.Nevertheless,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear.To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation.The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells.We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells.Subsequently,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded miR-21-5p.Finally,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously restored.These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p.miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome.This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves,and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.
基金supported by the National Natural Science Foundation of China,No.81202625Open Fund of Key Laboratory of Cardiovascular and Cerebrovascular Diseases Translational Medicine of China Three Gorges University of China,No.2016xnxg101
文摘The fermented Chinese formula Shuan-Tong-Ling is composed of radix puerariae(Gegen),salvia miltiorrhiza(Danshen),radix curcuma(Jianghuang),hawthorn(Shanzha),salvia chinensis(Shijianchuan),sinapis alba(Baijiezi),astragalus(Huangqi),panax japonicas(Zhujieshen),atractylodes macrocephala koidz(Baizhu),radix paeoniae alba(Baishao),bupleurum(Chaihu),chrysanthemum(Juhua),rhizoma cyperi(Xiangfu) and gastrodin(Tianma),whose aqueous extract was fermented with lactobacillus,bacillus aceticus and saccharomycetes.ShuanTong-Ling is a formula used to treat brain diseases including ischemic stroke,migraine,and vascular dementia.Shuan-Tong-Ling attenuated H_2O_2-induced oxidative stress in rat microvascular endothelial cells.However,the potential mechanism involved in these effects is poorly understood.Rats were intragastrically treated with 5.7 or 17.2 m L/kg Shuan-Tong-Ling for 7 days before middle cerebral artery occlusion was induced.The results indicated Shuan-Tong-Ling had a cerebral protective effect by reducing infarct volume and increasing neurological scores.Shuan-Tong-Ling also decreased tumor necrosis factor-α and interleukin-1β levels in the hippocampus on the ischemic side.In addition,Shuan-Tong-Ling upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of acetylated-protein 53 and Bax.Injection of 5 mg/kg silent information regulator 1(SIRT1) inhibitor EX527 into the subarachnoid space once every 2 days,four times,reversed the above changes.These results demonstrate that Shuan-Tong-Ling might benefit cerebral ischemia/reperfusion injury by reducing inflammation and apoptosis through activation of the SIRT1 signaling pathway.
文摘Background Metabolic syndrome is known to be a prothrombotic state. We undertook this study to examine a hypothesis that aspirin resistance may be associated with metabolic syndrome, and to assess other potential determinants of aspirin resistance in patients with cardiovascular disease (CVD). Methods A total of 469 elderly patients with CVD were recruited. One hundred and seventy-two patients with metabolic syndrome and 297 without metabolic syndrome (control group) received daily aspirin therapy (〉 75 mg) over one month. Platelet aggregation was measured by light transmission aggregometry (LTA). Aspirin resistance was defined as 〉 20% arachidonic acid (AA)- and 〉 70% adenosine diphosphate (ADP)-induced aggregation according to LTA. Aspirin semi-responders were defined as meeting one (but not both) of these criteria. Results By LTA, 38 of 469 (8.1%) patients were aspirin resistant. The prevalence of aspirin resistance was higher in the metabolic syndrome group compared with the control group [11.6 % vs. 6.6%, odds ratio (OR) = 2.039; 95% confidence interval (CI): 1.047-3.973]. In the multivariate logistic regression analysis, metabolic syndrome (OR = 4.951, 95% CI: 1.440-17.019, P = 0.011) was a significant risk factor for aspirin resistance. Conclusions A significant number of patients with CVD and metabolic syndrome are resistant to aspirin therapy. This might further increase the risk of cardiovascular morbidity and mortality in these patients.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related deaths worldwide,but there is a shortage of effective biomarkers for its diagnosis.AIM To explore blood exosomal micro ribonucleic acids(miRNAs)as potential biomarkers for HCC diagnosis.RESULTS The principal component analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of hepatitis B virus positive non-HCC patients through miR-3168 and miR-223-3p.The miRNA profiles also revealed the tumor stages of HCC patients.High expression of miR-455-5p and miR-30c-5p,which significantly correlated with better overall survival in tumor tissues,could also be detected in blood exosomes.Two pairs of miRNAs(miR-584-5p/miR-106-3p and miR-628-3p/miR-941)showed a 94.1%sensitivity and 68.4%specificity to differentiate HCC patients from non-HCC patients.The specificity of the combination was substantially influenced by alcohol consumption habits.CONCLUSION This study suggested that blood exosomal miRNAs can be used as new noninvasive diagnostic tools for HCC.However,their accuracy could be affected by tumor stage and alcohol consumption habits.
基金Supported by Qilu Hospital of Shandong University (No.201805049)
文摘AIM: To investigate the effects of green flickering light on refractive development and expression of muscarinic acetylcholine receptor(mAChR) M1 in the eyes of guinea pigs.METHODS: Thirty guinea pigs(15-20 days old) were randomly divided into three groups(n=10/group). Animals in group I were raised in a completely closed carton with green flickering light illumination. Those in group II were kept in the open top closed carton under normal natural light. Guinea pigs were raised in a sight-widen cage under normal natural light in group III. The refractive status and axial length were measured before and after 8 weeks' illumination. Moreover, total RNA extracted from retinal, choroidal, and scleral tissues were determined by real-time reverse transcription polymerase chain reaction(RT-PCR). The expressions of the receptor M1 were also explored in the retina, choroid, and sclera using immunohistochemistry.RESULTS: There was a remarkable reduction in refractive error and increase in axial length after 8-weeks' green flickering light stimulation(P〈0.001). The expression of M1 receptor mRNA in sclera and retina in myopia group were remarkably lower than that in group II and III(P〈0.01). Significant reduced expression of M1 receptor stimulated by green flickering light in retina and sclera tissues were also observed(P〈0.05). However, there was no M1 receptor expression in choroid in 3 groups.CONCLUSION: Myopia can be induced by 8 weeks' green flickering light exposure in the animal model. M1 receptor may be involved causally or protectively in myopia development.
基金the International Cooperative Project from the Ministry of Science and Technology of China (No. 2006DFA31030)the Bureau of Science and Technology of Zhejiang Province (No. 2006C32019)+1 种基金 HarvestPlus-China (No. 8022)the Program for Changjiang Scholars and Innovative Research Team in University of China (No. IRT0536)
文摘The objective of the present study was to compare the toxicity and availability of Fe(II) and Fe(III) to Caco-2 cells. Cellular damage was studied by measuring cell proliferation and lactate dehydrogenase (LDH) release. The activities of two major antioxidative enzymes [superoxide dismutase (SOD) and glutathione peroxidase (GPx)] and differentiation marker (alkaline phosphatase) were determined after the cells were exposed to different levels of iron salts. The cellular iron concentration was investigated to evaluate iron bioavailability. The results show that iron uptake of the cells treated with Fe(II) is significantly higher than that of the cells treated with Fe(III) (P<0.05). Fe(II) at a concentration >1.5 mmol/L was found to be more effective in reducing cellular viability than Fe(III). LDH release investigation suggests that Fe(II) can reduce stability of the cell membrane. The activities of SOD and GPx of the cells treated with Fe(II) were higher than those of the cells treated with Fe(III), although both of them increased with raising iron supply levels. The results indicate that both Fe(II) and Fe(III) could reduce the cellular antioxidase gene expression at high levels.
文摘Pyoderma gangrenosum(PG)is an uncommon ulcerative cutaneous condition of an unknown etiology and is often associated with immune diseases.However,PG rarely shows visceral involvement,especially in the kidney.A 20-year-old female presented with pedal edema and skin ulceration of both lower limbs.The skin lesion began as an erythematous plaque and then became a blister.She also complained of abdominal distension and a decreasing urine volume.Laboratory data showed high proteinuria,hypoalbuminemia and hyperlipidemia.Her skin and kidney were biopsied.The pathological results indicated PG and immunoglobulin A(IgA)nephropathy.The patient was finally cured with prednisolone in combination with cyclosporine A(CsA).
文摘BACKGROUND Craniometaphyseal dysplasia(CMD)is a rare genetic disorder.Autosomal dominant CMD(AD-CMD)is caused by mutations in the ANKH gene.Affected individuals typically have distinctive facial features including progressive thickening of the craniofacial bones.Treatment for AD-CMD primarily consists of surgical intervention to release compression of the cranial nerves and the brain stem/spinal cord.To alleviate progression of the clinical course and improve the quality of life in children waiting to undergo the necessary surgery,we investigated clinical changes in a diagnosed patient with AD-CMD over three years.CASE SUMMARY A 17-mo-old boy presented with progressive nasal obstruction,snoring and hearing loss symptoms.Physical examination showed enlargement of the head circumference and clinical features such as wide nasal bridge,paranasal bossing,widely spaced eyes with an increased bizygomatic width,and a prominent mandible.The patient underwent otolaryngological examination,endoscopy,hearing test,laboratory examination of phosphorus and bone metabolism,cranial and femoral computed tomography,X-ray and next-generation sequencing.The patient was diagnosed with AD-CMD due to p.Phe377 deletion(c.1129_1131del)on exon 9 of the ANKH gene.After adherence to a prescribed low-calcium diet,the boy’s alkaline phosphatase(ALP)levels continuously decreased to within the normal range.However,after 14 mo of dietary intervention,his parents altered his diet to an intermittent low-calcium diet to include milk and eggs.The patient’s ALP was slightly higher than normal after the dietary change but remained close to the normal range.His serum osteocalcin changed to within normal levels after dietary regulation for 33 mo.His serum combined beta C-terminal telopeptide of type I collagen also continuously decreased after the nutritional intervention,although still slightly higher than normal levels.Despite fluctuating blood test results,the boy’s nasal symptoms were markedly relieved and steadily improved after dietary intervention.No significant changes were found in the craniofacial bones by cranial radiography.Close monitoring of clinical features is still ongoing.Calcitriol treatment is currently under consideration and a surgical procedure is planned as necessary in the future.CONCLUSION We herein report the first Chinese case of AD-CMD with heterozygous mutation of p.Phe377 deletion(c.1129_1131del)on the ANKH gene.Biochemical alterations were significantly improved after dietary intervention indicating that a lowcalcium diet may be applied in pediatric AD-CMD patients with ANKH mutations to help alleviate phenotypic manifestations and improve the quality of life before surgical intervention.Further large scale studies are needed to replicate these findings and to establish the appropriate timing for nutritional and surgical interventions。
基金Capital medical development research fund (2017-3147)
文摘Objective:To explore the clinical effect of ambroxol hydrochloride combined with rehabilitation training on COPD and its effect on pulmonary function.Methods:92 patients with COPD from May 2017 to may 2019 were randomly divided into control group(n=46)and observation group(n=46).The control group was treated with oxygen inhalation,expectorant,antispasmodic,anti infection and so on.The observation group was treated with ambroxol hydrochloride combined with rehabilitation training on this basis.Blood gas,lung function and inflammatory factors were compared before and after treatment.Results:the levels of SaO2 and PaO2 in the two groups were significantly higher than those before treatment P There was significant difference between the two groups(P<0.05-0.01).Besides,the level of lung function related indexes in the observation group was significantly higher than that in the control group(P<0.05).Conclusion:ambroxol hydrochloride combined with rehabilitation training has a significant clinical effect on COPD,which can effectively improve the blood gas index and reduce the level of blood gas inflammatory factors,thus affecting the lung function of COPD patients.
文摘BACKGROUND Duodenum-preserving pancreatic head resection(DPPHR)is the choice of surgery for benign or low-grade malignant tumors of the pancreatic head.Laparoscopic DPPHR(LDPPHR)procedure can be improved by preoperative 3D model reconstruction and the use of intravenous indocyanine green fluorescent before surgery for real-time navigation with fluorescent display to guide the surgical dissection and prevention of from injury to vessels and biliary tract.CASE SUMMARY Here we report the successful short-and long-term outcomes after one year following LDPPHR for a 60-year lady who had an uneventful recovery and was discharged home one week after the surgery.CONCLUSION There was no bile leakage or pancreatic leakage or delayed gastric emptying.The histopathology report showed multiple cysts in the pancreatic head and localized pancreatic intraepithelial tumor lesions.The resected margin was free of tumor.
基金Supported by Science and Technology Planning Project of Shandong Province under the fund(No.2014WS012)
文摘Objective:To observe the protective effect of fasudil hydrochloride against acute renal injury in septicopyemia rats.Methods:A total of 60 Wister rats were included in the study and divided into control group(n = 10),model group(n = 25) and treatment group(n = 25).Model group and treatment group received intraperitoneal injection of endotoxin(ET) to establish acute renal injury models while the control group only received daily intraperitoneal injection of normal saline 1 mL.Five rats were taken out of model group and treatment group respectively at 1 h(T1),6 h(T2),12 h(T3),24 h(T4) and 48 h(T5),for intraperitoneal injection of ET 30 mg/kg.Treatment group received intraperitoneal injection of fasudil hydrochloride 30 mg/kg 1 h before injection of ET.For three groups,5 mL blood samples were collected from postcava for determination of serum creatinine and urea nitrogen levels at different time points.Concentrations of serum tumor necrosis factor and ET-1 were determined by using ELISA.The renal pathologic changes were observed under the microscope.Results:Serum creatinine levels in both model group and treatment group were significantly higher than control group at T2-T5(P < 0.05) while the levels in treatment group were significantly lower than control group at T3-T5(P < 0.05).At T2-T5,blood urea nitrogen levels in model group and treatment group were significantly higher than control group(P < 0.05) while the levels in treatment group were significantly lower than model group at T3-T5(P < 0.05).Concentrations of serum tumor necrosis factor in model group and treatment group were significantly higher than control group at T1-T5(P < 0.05) while the levels in treatment group were significantly lower than model group at T1-T5(P < 0.05).Serum ET-1 concentrations in model group and treatment group were significantly higher than control group at T1-T5(P <0.05) while the levels in treatment group at T1-T4 were significantly lower man model group(P <0.05).Rats in control group showed no swelling or hyperaemia in kidney cells but normal structure and normally arranged renal tubular epithelial cells.Obvious injury was observed in model group at T3 and renal tubular epithelial cells in disorder and at swelling condition,hyperaemia and angiectasis in glomerulus,degenerative opacities and vacuolar degeneration,and maximized injury were observed at T4.Injury in renal tissue in treatment group was significantly milder than model group.Conclusions:Fasudil hydrochloride has the significantly protective effect against acute renal injury in septicopyemia rats.
基金This work was supported by the Basic Research Project of the Ministry of Science and Technology of China(2012FY110300)MOST grant(2008BAD98B06).
文摘Phytochemical investigation of the aerial parts of Euphorbia sikkimensis led to the isolation of one new diterpenoids,named sikkimenoid E(1),together with thirteen other known compounds(2-14).Their structures were established by means of spectroscopic methods.Compound 2 was identified to be a trinortriterpenoid,and derived for the first time from a natural source.In this paper we reveal for the first time its comprehensive spectral data and NMR spectral assignment.Compound 4 showed anti-angiogenic activity with an IC_(50) value of 5.66μM in a zebrafish model,and compounds 5 and 6 exhibited cytotoxicity toward A549 cell line with IC_(50) values of 12.12 and 6.45μM,respectively.
基金supported financially by the Bureau of Science and Technology of Kunming City.
文摘Two new minor constituents,musinisins A(1)and B(2),together with five known compounds(3-7),were isolated from the aerial parts of Munronia sinica.Their structures were established by means of spectroscopic methods and the absolute stereochemistry of 1 was determined by single crystal X-ray experiment.Compound 4 showed antiangiogenic activity evaluated by a zebrafish model and apoptosis-inducing effect on A549 lung cancer cells.
文摘BACKGROUND:Blood hemoperfusion with resin adsorption can clean larger molecules that exceed the molecular weight cutoff of combined continuous veno-venous hemofiltration(CWH).Hence blood hemoperfusion with resin adsorption combined CWH(HP+CWH) has higher ability of mediator clearance,and can improve clinical outcomes in theory.This study aimed to investigate the effect of blood hemoperfusion with resin adsorption combined continuous veno-venous hemofiltration(HP+CWH) on plasm cytokines like TNF-α,IL-1β,IL-6,cellular immunity and prognosis in patients with multiple organ dysfunction syndrome(MODS).METHODS:This was a prospective,randomized clinical trial.A total of 30 patients who had been diagnosed with MODS were enrolled in this study.Patients were randomly allocated to routine treatment+HP+CWH group(treatment group) and routine treatment+only CWH group(control group).In the treatment group,patients received blood hemoperfusion with resin adsorption for 2hours,and then received CWH for 10 hours every day.In the control group,patients received CWH for 12 hours only every day.The patients in the two groups received blood purification therapy for three days.The plasma of patients in the treatment group was obtained at 0,2,12,24,26,36,48,50,60 hours,5th day,7th day and 10 th day,respectively.The plasma of patients in the control group was obtained at 0,12,24,36,48,60 hours,5th day,7th day and 10 th day,respectively.APACHE Ⅱscore,T-lymphocytes subpopulations,blood lactate acid concentration,heart rate,breathing rate,and oxygenation index were observed.RESULTS:Plasma cytokines like TNF-α,IL-1β,IL-6 decreased markedly after HP(P<0.01);T-lymphocytes subpopulations CD3+,CD4+,CD8+,CD4+/CD8+ increased after HP+CWH or only CWH.The plasma concentrations of TNF-α,IL-1β and IL-6 in the two groups were not markedly different at 12,36,and 50 hours.But on the 5th day,the plasma concentrations of TNF-α,IL-1β and IL-6 in the treatment group were lower than those in the control group(P<0.05).On the 28 th day,5patients died in the treatment group,and 6 patients in the control group.CONCLUSIONS:Both HP+CWH and CWH can clean plasma cytokines like TNF-α,IL-1β,and IL-6,and improve cellular immunity and clinical symptoms and signs of patients.Compared with only CWH,the plasma concentrations of TNF-α,IL-1β and IL-6 were lower on the 5th day,and patients have an increased survival rate on the 28 day in the HP+CWH group.