BACKGROUND Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic activity.During osteoporosis,bone mesenchymal stem cells(BMSCs)exhibit an increased abil...BACKGROUND Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic activity.During osteoporosis,bone mesenchymal stem cells(BMSCs)exhibit an increased ability to differentiate into adipocytes and a decreased ability to differentiate into osteoblasts,resulting in bone loss.Jumonji domain-containing 1C(JMJD1C)has been demonstrated to suppress osteoclastogenesis.AIM To examine the effect of JMJD1C on the osteogenesis of BMSCs and the potential underlying mechanism.METHODS BMSCs were isolated from mouse bone marrow tissues.Oil Red O staining,Alizarin red staining,alkaline phosphatase staining and the expression of adipo-genic and osteogenic-associated genes were assessed to determine the differen-tiation of BMSCs.Bone marrow-derived macrophages(BMMs)were incubated with receptor activator of nuclear factor-kappaΒligand to induce osteoclast differentiation,and osteoclast differen-tiation was confirmed by tartrate-resistant acid phosphatase staining.Other related genes were measured via reverse transcription coupled to the quantitative polymerase chain reaction and western blotting.Enzyme-linked immunosorbent assays were used to measure the levels of inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6 and interleukin-1 beta.RESULTS The osteogenic and adipogenic differentiation potential of BMSCs isolated from mouse bone marrow samples was evaluated.JMJD1C mRNA and protein expression was upregulated in BMSCs after osteoblast induction,while p-nuclear factor-κB(NF-κB)and inflammatory cytokines were not significantly altered.Knockdown of JMJD1C repressed osteogenic differentiation and enhanced NF-κB activation and inflammatory cytokine release in BMSCs.Moreover,JMJD1C expression decreased during BMM osteoclast differentiation.CONCLUSION The JMJD1C/NF-κB signaling pathway is potentially involved in BMSC osteogenic differentiation and may play vital roles in the pathogenesis of osteoporosis.展开更多
BACKGROUND Neuroendocrine tumors(NET)are rare heterogeneous tumors that arise from neuroendocrine cells throughout the body.Acromegaly,a rare and slowly progressive disorder,usually results from a growth hormone(GH)-s...BACKGROUND Neuroendocrine tumors(NET)are rare heterogeneous tumors that arise from neuroendocrine cells throughout the body.Acromegaly,a rare and slowly progressive disorder,usually results from a growth hormone(GH)-secreting pituitary adenoma.CASE SUMMARY We herein describe a 38-year-old patient who was initially diagnosed with diabetes.During colonoscopy,two bulges were identified and subsequently removed through endoscopic submucosal dissection.Following the surgical intervention,the excised tissue samples were examined and confirmed to be grade 2 NET.^(18)F-ALF-NOTATATE positron emission tomography-computed tomography(PET/CT)and 68Ga-DOTANOC PET/CT revealed metastases in the peri-intestinal lymph nodes,prompting laparoscopic low anterior resection with total mesorectal excision.The patient later returned to the hospital because of hyperglycemia and was found to have facial changes,namely a larger nose,thicker lips,and mandibular prognathism.Laboratory tests and magnetic resonance imaging(MRI)suggested a GH-secreting pituitary adenoma.The pituitary adenoma shrunk after treatment with octreotide and was neuroendoscopically resected via a trans-sphenoidal approach.Whole-exome sequencing analysis revealed no genetic abnormalities.The patient recovered well with no evidence of recurrence during follow-up.CONCLUSION ^(18)F-ALF-NOTATE PET/CT and MRI with pathological analysis can effectively diagnose rare cases of pituitary adenomas complicated with rectal NET.展开更多
The high-energy photon source(HEPS)is the first fourth-generation synchrotron light source facility in China.The HEPS injector consists of a linear accelerator(Linac)and a full energy booster.The booster captures the ...The high-energy photon source(HEPS)is the first fourth-generation synchrotron light source facility in China.The HEPS injector consists of a linear accelerator(Linac)and a full energy booster.The booster captures the electron beam from the Linac and increases its energy to the value required for the storage ring.The full-energy beam could be injected to the storage ring directly or after“high-energy accumulation.”On November 17,2023,the key booster parameters successfully reached their corresponding target values.These milestone results were achieved based on numerous contributions,including nearly a decade of physical design,years of equipment development and installation,and months of beam commissioning.As measured at the extraction energy of 6 GeV,the averaged beam current and emittance reached 8.57 mA with 5 bunches and 30.37 nm rad with a single-bunch charge of 5.58 nC,compared with the corresponding target values of 6.6 mA and 35 nm rad,respectively.This paper presents the physical design,equipment development,installation,and commissioning process of the HEPS booster.展开更多
BACKGROUND Schwannomas are uncommon tumors originating from Schwann cells,forming the neural sheath.They account for approximately 2%-6%of all mesenchymal tumors and are most commonly identified in peripheral nerve tr...BACKGROUND Schwannomas are uncommon tumors originating from Schwann cells,forming the neural sheath.They account for approximately 2%-6%of all mesenchymal tumors and are most commonly identified in peripheral nerve trunks,with rarity in the gastrointestinal tract.Among gastrointestinal locations,the stomach harbors the majority of nerve sheath tumors,while such occurrences in the sigmoid colon are exceptionally infrequent.CASE SUMMARY This study presented a clinical case involving a 60-year-old female patient who,during colonoscopy,was diagnosed with a submucosal lesion that was later identified as a nerve sheath tumor.The patient underwent surgical resection,and the diagnosis was confirmed through immunohistochemistry.This study highlighted an exceptionally uncommon occurrence of a nerve sheath tumor in the sigmoid colon,which was effectively managed within our department.Additionally,a comprehensive review of relevant studies was conducted.CONCLUSION The preoperative diagnosis of nerve sheath tumors poses challenges,as the definitive diagnosis still relies on pathology and immunohistochemistry.Although categorized as benign,these tumors have the potential to demonstrate malignant behavior.Consequently,the optimal treatment approach entails the complete surgical excision of the tumor,ensuring the absence of residual lesions at the margins.展开更多
AIM:To investigate the pathogenesis of biliary casts after liver transplantation relative to their morphology and biochemical markers.METHODS:The microstructure of biliary casts was assessed using scanning electron mi...AIM:To investigate the pathogenesis of biliary casts after liver transplantation relative to their morphology and biochemical markers.METHODS:The microstructure of biliary casts was assessed using scanning electron microscopy and Hematoxylin and eosin staining assessed their histology.The expression levels of CD3,CD5,CD34,CD68 and CD79a in these biliary casts were evaluated immunohistochemically.RESULTS:Biliary casts differed widely in their microstructure,with some containing blood vessels positive for CD34 and collagen fibers with positive Masson staining.Large numbers of neutrophils and other inflammatory cells were present,but only on the edge of the biliary casts;although the boundaries were clear without crossover.None of the biliary casts contained T-lymphocytes,B-lymphocytes,macrophages and other inflammatory cells.CONCLUSION:The microcostructure of biliary casts differed.Bacteria and acute rejection are not clearly related to their formation.展开更多
Fibrin glue is widely used in clinical practice and plays an important role in reducing postoperative complications.We report a case of a 65-year-old man, whose common bile duct was injured by fibrin glue, with a hist...Fibrin glue is widely used in clinical practice and plays an important role in reducing postoperative complications.We report a case of a 65-year-old man, whose common bile duct was injured by fibrin glue, with a history of failed laparoscopic cholecystectomy and open operation for uncontrolled laparoscopic bleeding.In view of thepersistent liver dysfunction, xanthochromia and skin itching, the patient was admitted to us for further management.Ultrasound, computed tomography, and magnetic resonance cholangiopancreatography(MRCP) revealed multiple stones in the common bile duct, and liver function tests confirmed the presence of obstructive jaundice and liver damage.Endoscopic retrograde cholangiopancreatography was unsuccessfully performed to remove choledocholithiasis, but a small amount of tissue was removed and pathologically confirmed as calcified biliary mucosa.This was followed by open surgery for suspicious cholangiocarcinoma.There was no evidence of cholangiocarcinoma, but the common bile duct wall had a defect of 8 mm × 10 mm at Calot's triangle.A hard, grid-like foreign body was removed, which proved to be solid fibrin glue.Subsequently, the residual choledocholithiasis was removed by a choledochoscopic procedure, and the common bile duct deletion was repaired by liver round ligament with T-tube drainage.Six months later, endoscopy was performed through the T-tube fistula and showed a well-repaired bile duct wall.Eight months later, MRCP confirmed no bile duct stenosis.A review of reported cases showed that fibrin glue is widely used in surgery, but it can also cause organ damage.Its mechanism may be related to discharge reactions.展开更多
Positron sources are one of the most important components of the injector of a circular electron positron collector(CEPC).The CEPC is designed as an e^(+)e^(−)collider for a Higgs factory.Its accelerator system is com...Positron sources are one of the most important components of the injector of a circular electron positron collector(CEPC).The CEPC is designed as an e^(+)e^(−)collider for a Higgs factory.Its accelerator system is composed of 100-km-long storage rings and an injector.The design goal of the positron source is to obtain positron beams with a bunch charge of 3 nC.The flux concentrator(FC)is one of the cores of the positron source.This paper reports the design,development,and measurements of an FC prototype system.The prototype includes an FC and an all-solid-state high-current pulse modulator.Preliminary tests show that the peak current on the FC can reach 15.5 kA,and the peak magnetic field can reach 6.2 T.The test results are consistent with the theoretical simulation.The FC system fulfills the requirements of the CEPC positron source as well as provides a reference for the development of similar devices both domestically and abroad.展开更多
OBJECTIVE Hypoxia is associated with many complicated pathophysiological and biochemical processes that integrated and regulated via the key gene,protein and endogenous metabolite levels.Up to date,the exact molecular...OBJECTIVE Hypoxia is associated with many complicated pathophysiological and biochemical processes that integrated and regulated via the key gene,protein and endogenous metabolite levels.Up to date,the exact molecular mechanism of hypoxia still remains unclear.In this work,we further explore the molecular mechanism of hypoxia and adaption to attenuate the damage in zebrafish model that have potential to resist hypoxic environment.METHODS The hypoxic zebrafish model was established in different concentration of oxygen with 3%,5%,10%,21%in water.The brain tissue was separated and the RNA-seq was used to identify the differentially expressed genes.The related endogenous metabolites profiles were obtained by LC-HDMS,and the multivariate statistics was applied to discover the important metabolites candidates in hypoxic zebrafish.The candidates were searched in HMDB,KEGG and Lipid Maps databases.RESULTS The zebrafish hypoxic model was successfully constructed via the different concentration of oxygen,temperature and hypoxic time.The activities of the related hypoxic metabolic enzymes and factors including HIF-1a,actate dehydrogenase(LDH)and citrate synthase(CS)were evaluated.Significant differences(P<0.05 and fold change>2)in the expression of 422 genes were observed between the normal and 3% hypoxic model.Among them,201 genes increased depended on the lower concentration of oxygen.53 metabolites were identified that had significant difference between the hypoxia and control groups(P<0.05,fold change>1.5 and VIP>1.5).The ten key metabolites were increased gradually while six compounds were decreased.The endogenous hypoxic metabolites of phenylalanine,D-glucosamine-6P and several important lipids with the relevant hub genes had similar change in hypoxic model.In addition,the metabolic pathways of phenylalanine,glutamine and glycolipid were influenced in both the levels of genes and metabolites.CONCLUSION The up-regulation of phenylalanine,D-glucosamine-6P and lipid may have further understanding of protective effect in hypoxia.Our data provided an insight to further reveal the hypoxia and adaptation mechanism.展开更多
Radio frequency windows are developed and evaluated for a 650 MHz continuous-wave multibeam klystron.Thin-pillbox windows with alumina and beryllia disks are designed with an average RF power of CW 400 kW.Results of a...Radio frequency windows are developed and evaluated for a 650 MHz continuous-wave multibeam klystron.Thin-pillbox windows with alumina and beryllia disks are designed with an average RF power of CW 400 kW.Results of a cold test and tuning procedures are described.The final measured S11 curves under the required bandwidth are less than-32.0 and-26.9 dB for alumina and beryllia windows,respectively.The windows are tested up to CW 143 kW for traveling waves and CW 110 kW for standing waves using a solid-state amplifier as an RF power source.Multipactor simulations for windows and benchmark studies for the thermal analysis of ceramic disks are introduced.展开更多
A gridded thermionic cathode electron gun was developed for the linear accelerator of the High Energy Photon Source(HEPS).An electron gun should provide a large maximum bunch charge with a wide adjustable range.To sat...A gridded thermionic cathode electron gun was developed for the linear accelerator of the High Energy Photon Source(HEPS).An electron gun should provide a large maximum bunch charge with a wide adjustable range.To satisfy these requirements,the shape of the electrode was optimized using a multi-objective genetic algorithm.A large bunch charge with an adjustable range was achieved using the grid-limited gun,the flow of which was analyzed using 3-D simulations.The electron gun has been manufactured and tested,and the measured data of the grid-limited current and simulation results are compared and discussed in this study.展开更多
The betatron tune is an important parameter in a storage ring to enable stable operation. A tune adjustment tool with a small impact on the beam dynamics is useful for user operation and machine studies. Therefore, a ...The betatron tune is an important parameter in a storage ring to enable stable operation. A tune adjustment tool with a small impact on the beam dynamics is useful for user operation and machine studies. Therefore, a tune knob is developed for the Hefei light source-II(HLS-II) storage ring. Owing to the compactness of the storage ring, a global adjustment mechanism is adopted. To reduce the impact on beam injection, only quadrupole families outside the injection section are used by the tune knob, and the b functions of the injection section remain unchanged. A code is developed based on the accelerator simulation software, MAD-X, to calculate the adjustment of the quadrupole strengths. The accelerator toolbox is used to double check the accuracy of the tune knob. Online measurement of the tune knob is also performed. The result shows that the tune knob works well when the tune is adjusted in a specific range. Betatron coupling measurement is also carried out, showing an application of the tune knob on machine studies. In this paper, the development of the tune knob and its experimental results in the HLS-II storage ring are reported in detail.展开更多
Harmonic RF cavities are commonly used in storage rings to lengthen the bunches and thus suppress the beam's instabilities and increase its Touschek lifetime. The voltage and phase of the electromagnetic fields in...Harmonic RF cavities are commonly used in storage rings to lengthen the bunches and thus suppress the beam's instabilities and increase its Touschek lifetime. The voltage and phase of the electromagnetic fields in the harmonic cavity are of great importance for stretching the bunch. In the Hefei Light Source storage ring, a passive fourth-harmonic cavity is installed, and the cavity is monitored and controlled by an analog control module provided by its manufacturer. To vary and maintain the voltage of the harmonic cavity in a more effective way, a digital proportional, integral, and derivative feedback system based on the Experimental Physics and Industrial Control System is developed on top of the analog control module. This paper reports the details of the development of this voltage control system. Some test and operational results are also presented.展开更多
Purpose The High-Energy Photon Source(HEPS)is a 6 GeV storage ring-based light source under construction in Beijing,China.Its accelerator consists of a 6 GeV storage ring,a full-energy booster,an S-band normal-conduct...Purpose The High-Energy Photon Source(HEPS)is a 6 GeV storage ring-based light source under construction in Beijing,China.Its accelerator consists of a 6 GeV storage ring,a full-energy booster,an S-band normal-conducting 500 MeV linac,and three transport lines.As the beginning of HEPS,a stable linac is quite important,which needs a qualified waveguide distribution system to transmit microwave power from klystrons to accelerating structures.Methods Installation and high-power conditioning of the HEPS linac were performed from February to September 2022.The assembly and conditioning of the waveguide distribution system were completed in April and July,respectively.The design of the waveguide distribution system began in 2018 and was finalized at the end of 2020 after multiple iterations.Results Owing to careful design,fabrication,and assembly preparation,the assembly and conditioning of the system proceeded smoothly and considerable time was saved.Conclusion The entire process from the design to the ultimate realization of the system is introduced in detail in this paper.Satisfactory measurement results were obtained for some waveguide components.展开更多
Basonuclin(BNC1)is expressed primarily in proliferative keratinocytes and gametogenic cells.However,its roles in spermatogenesis and testicular aging were not dear.Previously we discovered a heterozygous BNC1 truncati...Basonuclin(BNC1)is expressed primarily in proliferative keratinocytes and gametogenic cells.However,its roles in spermatogenesis and testicular aging were not dear.Previously we discovered a heterozygous BNC1 truncation mutation in a premature ovarian insufficiency pedigree.In this study,we found that male mice carrying the truncation mutation exhibited progressively fertility loss and testicular premature aging.Genome-wide expression profiling and direct binding studies(by chromatin immunoprecipitation sequencing)with BNC1 in mouse testis identified several spermatogenesis-specific gene promoters targeted by BNC1 including kelch-like family member 10(Klhl1O),testis expressed 14(Tex14)9 and spermatogenesis and centriole associated 1(Spatcl).Moreover,biochemical analysis showed that BNC1 was associated with TATA-box binding protein-associated factor 7 like(TAF7L),a germ cell-specific paralogue of the transcription factor IID subunit TAF7,both in vitro and in testis,suggesting that BNC1 might directly cooperate with TAF7L to regulate spermatogenesis.The truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex,thus,disturbing expression of related genes and leading to testicular premature aging.Similarly,expressions of Y-box-binding protein 2(YBX2),outer dense fiber of sperm tails 1(ODfl),and glyceraldehyde-3-phosphate dehydrogenase,spermatogenic(GAPDHS)were significantly decreased in the testis of men with non-obstructive azoospermia.The present study adds to the understanding of the physiology of male reproductive aging and the mechanism of spermatogenic failure in infertile men.展开更多
Background:Mesenchymal stem or stromal cells(MSCs)derived from the induced pluripotent stem cells(iPSCs)have uniform biological activity,which makes the clinical application of MSCs in bone repair possible.Culturing t...Background:Mesenchymal stem or stromal cells(MSCs)derived from the induced pluripotent stem cells(iPSCs)have uniform biological activity,which makes the clinical application of MSCs in bone repair possible.Culturing the iPSC-MSCs onto osteoconductive materials is a promising tissue engineering-based strategy in bone regeneration.The aim of this work was to evaluate the effects of semaphorin 3A(Sema3A)and hypoxia inducible factor 1 subunit alpha(HIF1α)co-overexpression on the survival and osteogenic differentiation of iPSC-MSCs.Methods:Sema3A and HIF1αwere linked together with the three(GGGGS;G,glycine;S,serine)peptide fragment,and their co-expression in iPSC-MSCs was mediated by a lentiviral vector.The fusion protein retained the immune reactivity for both Sema3A and HIF1αas determined with Western blotting.iPSC-MSCs were infected with overexpression lentivirus(oeLenti)as negative control,oeLenti-Sema3A,oeLenti-HIF1αor oeLenti-Sema3A-HIF1αlentiviruses.Results:Sema3A overexpression alone promoted the osteogenic differentiation of iPSC-MSCs(the activity and/or expression of osteoblast markers,such as alkaline phosphatase,osteopontin,and osteocalcin,were upregulated),and suppressed cell survival.The Sema3A-HIF1αfusion protein showed a comparable osteoconductive effect to that of Sema3A without reducing cell survival.We further seeded iPSC-MSCs modified by SemaA-HIF1αoverexpression onto hydroxyapatite(HA)scaffolds,and evaluated their growth and differentiation on this three-dimensional material.Additional data indicated that,as compared to iPSC-MSCs cultured in ordinary two-dimensional dishes,cells cultured in HA scaffolds grew(blank vs.HA scaffolds:0.83 vs.1.39 for survival)and differentiated better(blank vs.HA scaffolds:11.29 vs.16.62 for alkaline phosphatase activity).Conclusion:Modifying iPSC-MSCs with pro-osteogenic(Sema3A)and pro-survival(HIF1α)factors may represent a promising strategy to optimize tissue engineering-based strategy in bone repair.展开更多
Background：Melanoma is a type of cancer that develops from the pigment-containing cells.Until now,its pathological mechanisms remain largely unknown.The aim of this study was to identify metastasis-related microRNA ...Background：Melanoma is a type of cancer that develops from the pigment-containing cells.Until now,its pathological mechanisms remain largely unknown.The aim of this study was to identify metastasis-related microRNA （miRNAs） and gain an understanding of the biological functions in the metastasis of melanoma.Methods：We searched the PubMed and Gene Expression Omnibus database to collect miRNA expression profiling datasets about melanoma,with key words of＂melanoma＂,＂miRNA＂,＂microarray＂,and ＂gene expression profiling＂.Only the original experimental works published before June 2016 for analyzing the metastasis of melanoma were retained,other nonhuman studies,reviews,and meta-analyses were removed.We performed a meta-analysis to explore the differentially expressed miRNA between metastatic and nonmetastatic samples.Moreover,we predicted target genes of the miRNAs to study their biological roles for these miRNAs.Results：We identified a total of 63 significantly differentially expressed miRNAs by meta-analysis of the melanoma expression profiling data.The regulatory network constructed by using these miRNAs and the predicted targets identified several key genes involved in the metastasis of melanoma.Functional annotation of these genes indicated that they are mainly enriched in some biological pathways such as mitogen-activated protein kinase signaling pathway,cell junction,and focal adhesion.Conclusions：By collecting the miRNA expression datasets from different platforms,multiple biological markers were identified for the metastasis of melanoma.This study provided novel insights into the molecular mechanisms underlying this disease,thereby aiding the diagnosis and treatment of the disease.展开更多
With the advances in accelerator science and technology in recent decades, the accelerator commumty has focused on the development of next-generation light sources, for example diffraction-limited storage rings （DLSR...With the advances in accelerator science and technology in recent decades, the accelerator commumty has focused on the development of next-generation light sources, for example diffraction-limited storage rings （DLSRs）, which require precision control of the electron beam energy and betatron tunes. This work is aimed at understanding magnet hysteresis effects on the electron beam energy and lattice focusing in circular accelerators, and developing new methods to gain better control of these effects. In this paper, we will report our recent experimental study of the magnetic hysteresis effects and their impacts on the Duke storage ring lattice using the transverse feedback based precision tune measurement system. The major magnet hysteresis effects associated with magnet normalization and lattice ramping are carefully studied to determine an effective procedure for lattice preparation while maintaining a high degree of reproducibility of lattice focusing. The local hysteresis effects are also studied by measuring the betatron tune shifts which result from adjusting the setting of a quadrupole. A new technique has been developed to precisely recover the focusing strength of the quadrupole by hysteresis effect. returning it to a proper setting to overcome the local展开更多
基金2018 Henan Medical Science and Technology Research Plan Project,China,No.SBGJ2018019.
文摘BACKGROUND Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic activity.During osteoporosis,bone mesenchymal stem cells(BMSCs)exhibit an increased ability to differentiate into adipocytes and a decreased ability to differentiate into osteoblasts,resulting in bone loss.Jumonji domain-containing 1C(JMJD1C)has been demonstrated to suppress osteoclastogenesis.AIM To examine the effect of JMJD1C on the osteogenesis of BMSCs and the potential underlying mechanism.METHODS BMSCs were isolated from mouse bone marrow tissues.Oil Red O staining,Alizarin red staining,alkaline phosphatase staining and the expression of adipo-genic and osteogenic-associated genes were assessed to determine the differen-tiation of BMSCs.Bone marrow-derived macrophages(BMMs)were incubated with receptor activator of nuclear factor-kappaΒligand to induce osteoclast differentiation,and osteoclast differen-tiation was confirmed by tartrate-resistant acid phosphatase staining.Other related genes were measured via reverse transcription coupled to the quantitative polymerase chain reaction and western blotting.Enzyme-linked immunosorbent assays were used to measure the levels of inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6 and interleukin-1 beta.RESULTS The osteogenic and adipogenic differentiation potential of BMSCs isolated from mouse bone marrow samples was evaluated.JMJD1C mRNA and protein expression was upregulated in BMSCs after osteoblast induction,while p-nuclear factor-κB(NF-κB)and inflammatory cytokines were not significantly altered.Knockdown of JMJD1C repressed osteogenic differentiation and enhanced NF-κB activation and inflammatory cytokine release in BMSCs.Moreover,JMJD1C expression decreased during BMM osteoclast differentiation.CONCLUSION The JMJD1C/NF-κB signaling pathway is potentially involved in BMSC osteogenic differentiation and may play vital roles in the pathogenesis of osteoporosis.
文摘BACKGROUND Neuroendocrine tumors(NET)are rare heterogeneous tumors that arise from neuroendocrine cells throughout the body.Acromegaly,a rare and slowly progressive disorder,usually results from a growth hormone(GH)-secreting pituitary adenoma.CASE SUMMARY We herein describe a 38-year-old patient who was initially diagnosed with diabetes.During colonoscopy,two bulges were identified and subsequently removed through endoscopic submucosal dissection.Following the surgical intervention,the excised tissue samples were examined and confirmed to be grade 2 NET.^(18)F-ALF-NOTATATE positron emission tomography-computed tomography(PET/CT)and 68Ga-DOTANOC PET/CT revealed metastases in the peri-intestinal lymph nodes,prompting laparoscopic low anterior resection with total mesorectal excision.The patient later returned to the hospital because of hyperglycemia and was found to have facial changes,namely a larger nose,thicker lips,and mandibular prognathism.Laboratory tests and magnetic resonance imaging(MRI)suggested a GH-secreting pituitary adenoma.The pituitary adenoma shrunk after treatment with octreotide and was neuroendoscopically resected via a trans-sphenoidal approach.Whole-exome sequencing analysis revealed no genetic abnormalities.The patient recovered well with no evidence of recurrence during follow-up.CONCLUSION ^(18)F-ALF-NOTATE PET/CT and MRI with pathological analysis can effectively diagnose rare cases of pituitary adenomas complicated with rectal NET.
基金This work was supported by the National Natural Science Foundation of China(No.12005239).
文摘The high-energy photon source(HEPS)is the first fourth-generation synchrotron light source facility in China.The HEPS injector consists of a linear accelerator(Linac)and a full energy booster.The booster captures the electron beam from the Linac and increases its energy to the value required for the storage ring.The full-energy beam could be injected to the storage ring directly or after“high-energy accumulation.”On November 17,2023,the key booster parameters successfully reached their corresponding target values.These milestone results were achieved based on numerous contributions,including nearly a decade of physical design,years of equipment development and installation,and months of beam commissioning.As measured at the extraction energy of 6 GeV,the averaged beam current and emittance reached 8.57 mA with 5 bunches and 30.37 nm rad with a single-bunch charge of 5.58 nC,compared with the corresponding target values of 6.6 mA and 35 nm rad,respectively.This paper presents the physical design,equipment development,installation,and commissioning process of the HEPS booster.
文摘BACKGROUND Schwannomas are uncommon tumors originating from Schwann cells,forming the neural sheath.They account for approximately 2%-6%of all mesenchymal tumors and are most commonly identified in peripheral nerve trunks,with rarity in the gastrointestinal tract.Among gastrointestinal locations,the stomach harbors the majority of nerve sheath tumors,while such occurrences in the sigmoid colon are exceptionally infrequent.CASE SUMMARY This study presented a clinical case involving a 60-year-old female patient who,during colonoscopy,was diagnosed with a submucosal lesion that was later identified as a nerve sheath tumor.The patient underwent surgical resection,and the diagnosis was confirmed through immunohistochemistry.This study highlighted an exceptionally uncommon occurrence of a nerve sheath tumor in the sigmoid colon,which was effectively managed within our department.Additionally,a comprehensive review of relevant studies was conducted.CONCLUSION The preoperative diagnosis of nerve sheath tumors poses challenges,as the definitive diagnosis still relies on pathology and immunohistochemistry.Although categorized as benign,these tumors have the potential to demonstrate malignant behavior.Consequently,the optimal treatment approach entails the complete surgical excision of the tumor,ensuring the absence of residual lesions at the margins.
文摘AIM:To investigate the pathogenesis of biliary casts after liver transplantation relative to their morphology and biochemical markers.METHODS:The microstructure of biliary casts was assessed using scanning electron microscopy and Hematoxylin and eosin staining assessed their histology.The expression levels of CD3,CD5,CD34,CD68 and CD79a in these biliary casts were evaluated immunohistochemically.RESULTS:Biliary casts differed widely in their microstructure,with some containing blood vessels positive for CD34 and collagen fibers with positive Masson staining.Large numbers of neutrophils and other inflammatory cells were present,but only on the edge of the biliary casts;although the boundaries were clear without crossover.None of the biliary casts contained T-lymphocytes,B-lymphocytes,macrophages and other inflammatory cells.CONCLUSION:The microcostructure of biliary casts differed.Bacteria and acute rejection are not clearly related to their formation.
文摘Fibrin glue is widely used in clinical practice and plays an important role in reducing postoperative complications.We report a case of a 65-year-old man, whose common bile duct was injured by fibrin glue, with a history of failed laparoscopic cholecystectomy and open operation for uncontrolled laparoscopic bleeding.In view of thepersistent liver dysfunction, xanthochromia and skin itching, the patient was admitted to us for further management.Ultrasound, computed tomography, and magnetic resonance cholangiopancreatography(MRCP) revealed multiple stones in the common bile duct, and liver function tests confirmed the presence of obstructive jaundice and liver damage.Endoscopic retrograde cholangiopancreatography was unsuccessfully performed to remove choledocholithiasis, but a small amount of tissue was removed and pathologically confirmed as calcified biliary mucosa.This was followed by open surgery for suspicious cholangiocarcinoma.There was no evidence of cholangiocarcinoma, but the common bile duct wall had a defect of 8 mm × 10 mm at Calot's triangle.A hard, grid-like foreign body was removed, which proved to be solid fibrin glue.Subsequently, the residual choledocholithiasis was removed by a choledochoscopic procedure, and the common bile duct deletion was repaired by liver round ligament with T-tube drainage.Six months later, endoscopy was performed through the T-tube fistula and showed a well-repaired bile duct wall.Eight months later, MRCP confirmed no bile duct stenosis.A review of reported cases showed that fibrin glue is widely used in surgery, but it can also cause organ damage.Its mechanism may be related to discharge reactions.
基金This work was supported by the National Key Programme for S&T Research and Development(No.2016YFA0400400)the Youth Innovation Promotion Association CAS(2019016).
文摘Positron sources are one of the most important components of the injector of a circular electron positron collector(CEPC).The CEPC is designed as an e^(+)e^(−)collider for a Higgs factory.Its accelerator system is composed of 100-km-long storage rings and an injector.The design goal of the positron source is to obtain positron beams with a bunch charge of 3 nC.The flux concentrator(FC)is one of the cores of the positron source.This paper reports the design,development,and measurements of an FC prototype system.The prototype includes an FC and an all-solid-state high-current pulse modulator.Preliminary tests show that the peak current on the FC can reach 15.5 kA,and the peak magnetic field can reach 6.2 T.The test results are consistent with the theoretical simulation.The FC system fulfills the requirements of the CEPC positron source as well as provides a reference for the development of similar devices both domestically and abroad.
基金supported by National Natural Science Foundation of China(81573683 and 81173121)
文摘OBJECTIVE Hypoxia is associated with many complicated pathophysiological and biochemical processes that integrated and regulated via the key gene,protein and endogenous metabolite levels.Up to date,the exact molecular mechanism of hypoxia still remains unclear.In this work,we further explore the molecular mechanism of hypoxia and adaption to attenuate the damage in zebrafish model that have potential to resist hypoxic environment.METHODS The hypoxic zebrafish model was established in different concentration of oxygen with 3%,5%,10%,21%in water.The brain tissue was separated and the RNA-seq was used to identify the differentially expressed genes.The related endogenous metabolites profiles were obtained by LC-HDMS,and the multivariate statistics was applied to discover the important metabolites candidates in hypoxic zebrafish.The candidates were searched in HMDB,KEGG and Lipid Maps databases.RESULTS The zebrafish hypoxic model was successfully constructed via the different concentration of oxygen,temperature and hypoxic time.The activities of the related hypoxic metabolic enzymes and factors including HIF-1a,actate dehydrogenase(LDH)and citrate synthase(CS)were evaluated.Significant differences(P<0.05 and fold change>2)in the expression of 422 genes were observed between the normal and 3% hypoxic model.Among them,201 genes increased depended on the lower concentration of oxygen.53 metabolites were identified that had significant difference between the hypoxia and control groups(P<0.05,fold change>1.5 and VIP>1.5).The ten key metabolites were increased gradually while six compounds were decreased.The endogenous hypoxic metabolites of phenylalanine,D-glucosamine-6P and several important lipids with the relevant hub genes had similar change in hypoxic model.In addition,the metabolic pathways of phenylalanine,glutamine and glycolipid were influenced in both the levels of genes and metabolites.CONCLUSION The up-regulation of phenylalanine,D-glucosamine-6P and lipid may have further understanding of protective effect in hypoxia.Our data provided an insight to further reveal the hypoxia and adaptation mechanism.
文摘Radio frequency windows are developed and evaluated for a 650 MHz continuous-wave multibeam klystron.Thin-pillbox windows with alumina and beryllia disks are designed with an average RF power of CW 400 kW.Results of a cold test and tuning procedures are described.The final measured S11 curves under the required bandwidth are less than-32.0 and-26.9 dB for alumina and beryllia windows,respectively.The windows are tested up to CW 143 kW for traveling waves and CW 110 kW for standing waves using a solid-state amplifier as an RF power source.Multipactor simulations for windows and benchmark studies for the thermal analysis of ceramic disks are introduced.
文摘A gridded thermionic cathode electron gun was developed for the linear accelerator of the High Energy Photon Source(HEPS).An electron gun should provide a large maximum bunch charge with a wide adjustable range.To satisfy these requirements,the shape of the electrode was optimized using a multi-objective genetic algorithm.A large bunch charge with an adjustable range was achieved using the grid-limited gun,the flow of which was analyzed using 3-D simulations.The electron gun has been manufactured and tested,and the measured data of the grid-limited current and simulation results are compared and discussed in this study.
基金supported by the National Natural Science Foundation of China(Nos.11375177 and 11705200)
文摘The betatron tune is an important parameter in a storage ring to enable stable operation. A tune adjustment tool with a small impact on the beam dynamics is useful for user operation and machine studies. Therefore, a tune knob is developed for the Hefei light source-II(HLS-II) storage ring. Owing to the compactness of the storage ring, a global adjustment mechanism is adopted. To reduce the impact on beam injection, only quadrupole families outside the injection section are used by the tune knob, and the b functions of the injection section remain unchanged. A code is developed based on the accelerator simulation software, MAD-X, to calculate the adjustment of the quadrupole strengths. The accelerator toolbox is used to double check the accuracy of the tune knob. Online measurement of the tune knob is also performed. The result shows that the tune knob works well when the tune is adjusted in a specific range. Betatron coupling measurement is also carried out, showing an application of the tune knob on machine studies. In this paper, the development of the tune knob and its experimental results in the HLS-II storage ring are reported in detail.
基金supported by the National Natural Science Foundation of China(No.11375177)
文摘Harmonic RF cavities are commonly used in storage rings to lengthen the bunches and thus suppress the beam's instabilities and increase its Touschek lifetime. The voltage and phase of the electromagnetic fields in the harmonic cavity are of great importance for stretching the bunch. In the Hefei Light Source storage ring, a passive fourth-harmonic cavity is installed, and the cavity is monitored and controlled by an analog control module provided by its manufacturer. To vary and maintain the voltage of the harmonic cavity in a more effective way, a digital proportional, integral, and derivative feedback system based on the Experimental Physics and Industrial Control System is developed on top of the analog control module. This paper reports the details of the development of this voltage control system. Some test and operational results are also presented.
基金Funded by Youth Innovation Promotion Association CAS(2020015)and the HEPS project.
文摘Purpose The High-Energy Photon Source(HEPS)is a 6 GeV storage ring-based light source under construction in Beijing,China.Its accelerator consists of a 6 GeV storage ring,a full-energy booster,an S-band normal-conducting 500 MeV linac,and three transport lines.As the beginning of HEPS,a stable linac is quite important,which needs a qualified waveguide distribution system to transmit microwave power from klystrons to accelerating structures.Methods Installation and high-power conditioning of the HEPS linac were performed from February to September 2022.The assembly and conditioning of the waveguide distribution system were completed in April and July,respectively.The design of the waveguide distribution system began in 2018 and was finalized at the end of 2020 after multiple iterations.Results Owing to careful design,fabrication,and assembly preparation,the assembly and conditioning of the system proceeded smoothly and considerable time was saved.Conclusion The entire process from the design to the ultimate realization of the system is introduced in detail in this paper.Satisfactory measurement results were obtained for some waveguide components.
基金This work was supported by the National Key Research and Development Program of China(2018YFC1005003,2017YFC1001003,and 2017YFC1001303)the National Natural Science Foundation of China(81471421,81401219,and 81701461)+3 种基金The Fundamental Research Funds for the Central Universities,Natural Science Foundation of Zhejiang Province(Q19H040040)Key Research Program of Zhejiang Provincial Natural Science Foundation(LZ18H040001)Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai(2018YQ39)Zhejiang University Education Foundation Global Partnership Fund.
文摘Basonuclin(BNC1)is expressed primarily in proliferative keratinocytes and gametogenic cells.However,its roles in spermatogenesis and testicular aging were not dear.Previously we discovered a heterozygous BNC1 truncation mutation in a premature ovarian insufficiency pedigree.In this study,we found that male mice carrying the truncation mutation exhibited progressively fertility loss and testicular premature aging.Genome-wide expression profiling and direct binding studies(by chromatin immunoprecipitation sequencing)with BNC1 in mouse testis identified several spermatogenesis-specific gene promoters targeted by BNC1 including kelch-like family member 10(Klhl1O),testis expressed 14(Tex14)9 and spermatogenesis and centriole associated 1(Spatcl).Moreover,biochemical analysis showed that BNC1 was associated with TATA-box binding protein-associated factor 7 like(TAF7L),a germ cell-specific paralogue of the transcription factor IID subunit TAF7,both in vitro and in testis,suggesting that BNC1 might directly cooperate with TAF7L to regulate spermatogenesis.The truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex,thus,disturbing expression of related genes and leading to testicular premature aging.Similarly,expressions of Y-box-binding protein 2(YBX2),outer dense fiber of sperm tails 1(ODfl),and glyceraldehyde-3-phosphate dehydrogenase,spermatogenic(GAPDHS)were significantly decreased in the testis of men with non-obstructive azoospermia.The present study adds to the understanding of the physiology of male reproductive aging and the mechanism of spermatogenic failure in infertile men.
基金This work was supported by a grant from the National Natural Science Foundation of China(No.81601726).
文摘Background:Mesenchymal stem or stromal cells(MSCs)derived from the induced pluripotent stem cells(iPSCs)have uniform biological activity,which makes the clinical application of MSCs in bone repair possible.Culturing the iPSC-MSCs onto osteoconductive materials is a promising tissue engineering-based strategy in bone regeneration.The aim of this work was to evaluate the effects of semaphorin 3A(Sema3A)and hypoxia inducible factor 1 subunit alpha(HIF1α)co-overexpression on the survival and osteogenic differentiation of iPSC-MSCs.Methods:Sema3A and HIF1αwere linked together with the three(GGGGS;G,glycine;S,serine)peptide fragment,and their co-expression in iPSC-MSCs was mediated by a lentiviral vector.The fusion protein retained the immune reactivity for both Sema3A and HIF1αas determined with Western blotting.iPSC-MSCs were infected with overexpression lentivirus(oeLenti)as negative control,oeLenti-Sema3A,oeLenti-HIF1αor oeLenti-Sema3A-HIF1αlentiviruses.Results:Sema3A overexpression alone promoted the osteogenic differentiation of iPSC-MSCs(the activity and/or expression of osteoblast markers,such as alkaline phosphatase,osteopontin,and osteocalcin,were upregulated),and suppressed cell survival.The Sema3A-HIF1αfusion protein showed a comparable osteoconductive effect to that of Sema3A without reducing cell survival.We further seeded iPSC-MSCs modified by SemaA-HIF1αoverexpression onto hydroxyapatite(HA)scaffolds,and evaluated their growth and differentiation on this three-dimensional material.Additional data indicated that,as compared to iPSC-MSCs cultured in ordinary two-dimensional dishes,cells cultured in HA scaffolds grew(blank vs.HA scaffolds:0.83 vs.1.39 for survival)and differentiated better(blank vs.HA scaffolds:11.29 vs.16.62 for alkaline phosphatase activity).Conclusion:Modifying iPSC-MSCs with pro-osteogenic(Sema3A)and pro-survival(HIF1α)factors may represent a promising strategy to optimize tissue engineering-based strategy in bone repair.
文摘Background：Melanoma is a type of cancer that develops from the pigment-containing cells.Until now,its pathological mechanisms remain largely unknown.The aim of this study was to identify metastasis-related microRNA （miRNAs） and gain an understanding of the biological functions in the metastasis of melanoma.Methods：We searched the PubMed and Gene Expression Omnibus database to collect miRNA expression profiling datasets about melanoma,with key words of＂melanoma＂,＂miRNA＂,＂microarray＂,and ＂gene expression profiling＂.Only the original experimental works published before June 2016 for analyzing the metastasis of melanoma were retained,other nonhuman studies,reviews,and meta-analyses were removed.We performed a meta-analysis to explore the differentially expressed miRNA between metastatic and nonmetastatic samples.Moreover,we predicted target genes of the miRNAs to study their biological roles for these miRNAs.Results：We identified a total of 63 significantly differentially expressed miRNAs by meta-analysis of the melanoma expression profiling data.The regulatory network constructed by using these miRNAs and the predicted targets identified several key genes involved in the metastasis of melanoma.Functional annotation of these genes indicated that they are mainly enriched in some biological pathways such as mitogen-activated protein kinase signaling pathway,cell junction,and focal adhesion.Conclusions：By collecting the miRNA expression datasets from different platforms,multiple biological markers were identified for the metastasis of melanoma.This study provided novel insights into the molecular mechanisms underlying this disease,thereby aiding the diagnosis and treatment of the disease.
基金Supported by National Natural Science Foundation of China(11175180,11475167)US DOE(DE-FG02-97ER41033)
文摘With the advances in accelerator science and technology in recent decades, the accelerator commumty has focused on the development of next-generation light sources, for example diffraction-limited storage rings （DLSRs）, which require precision control of the electron beam energy and betatron tunes. This work is aimed at understanding magnet hysteresis effects on the electron beam energy and lattice focusing in circular accelerators, and developing new methods to gain better control of these effects. In this paper, we will report our recent experimental study of the magnetic hysteresis effects and their impacts on the Duke storage ring lattice using the transverse feedback based precision tune measurement system. The major magnet hysteresis effects associated with magnet normalization and lattice ramping are carefully studied to determine an effective procedure for lattice preparation while maintaining a high degree of reproducibility of lattice focusing. The local hysteresis effects are also studied by measuring the betatron tune shifts which result from adjusting the setting of a quadrupole. A new technique has been developed to precisely recover the focusing strength of the quadrupole by hysteresis effect. returning it to a proper setting to overcome the local
