BACKGROUND Gastrointestinal symptoms are common in patients with uremia undergoing hemodialysis,and these symptoms seriously affect patients'prognosis.AIM To assess the occurrence and factors influencing gastroint...BACKGROUND Gastrointestinal symptoms are common in patients with uremia undergoing hemodialysis,and these symptoms seriously affect patients'prognosis.AIM To assess the occurrence and factors influencing gastrointestinal symptoms in patients with uremia undergoing hemodialysis.METHODS We retrospectively selected 98 patients with uremia who underwent regular hemo-dialysis treatment in the blood purification center of our hospital from December 2022 to December 2023.The gastrointestinal symptoms and scores of each dimension were evaluated using the Gastrointestinal Symptom Grading Scale(GSRS).Patients were divided into gastrointestinal symptoms and no gastrointestinal symptom groups according to whether they had gastrointestinal symptoms.The factors that may affect gastrointestinal symptoms were identified by single-factor analysis.Multiple logistic regression analysis was performed to identify independent risk factors for gastrointestinal symptoms.RESULTS Gastrointestinal symptoms included indigestion,constipation,reflux,diarrhea,abdominal pain,and eating disorders,and the total average GSRS score was 1.35±0.47.This study showed that age,number of tablets,dialysis time,glucocorticoid,parathyroid hormone(PTH),combined diabetes mellitus and C-reactive protein(CRP)were independent risk factors for gastrointestinal symptoms in patients with uremia undergoing hemodialysis,whereas body mass index(BMI),hemoglobin(Hb),and urea clearance index were independent protective factors(P<0.05).CONCLUSION Gastrointestinal symptoms are mostly mild in patients with uremia undergoing hemodialysis,most commonly including dyspepsia,eating disorders,and gastroesophageal reflux.The independent influencing factors mainly include the BMI,age,number of pills taken,dialysis time,urea clearance index,Hb,use of glucocorticoids,and thyroid hormone level.PTH,CRP,and diabetes are clinically related factors influencing the occurrence of gastrointestinal symptoms,and targeted prevention can be performed.展开更多
BACKGROUND Recently,stem cell therapy has been extensively studied as a promising treatment for decompensated liver cirrhosis(DLC).Technological advances in endoscopic ultrasonography(EUS)have facilitated EUS-guided p...BACKGROUND Recently,stem cell therapy has been extensively studied as a promising treatment for decompensated liver cirrhosis(DLC).Technological advances in endoscopic ultrasonography(EUS)have facilitated EUS-guided portal vein(PV)access,through which stem cells can be precisely infused.AIM To investigate the feasibility and safety of fresh autologous bone marrow injection into the PV under EUS guidance in patients with DLC.METHODS Five patients with DLC were enrolled in this study after they provided written informed consent.EUS-guided intraportal bone marrow injection with a 22G FNA needle was performed using a transgastric,transhepatic approach.Several parameters were assessed before and after the procedure for a follow-up period of 12 mo.RESULTS Four males and one female with a mean age of 51 years old participated in this study.All patients had hepatitis B virus-related DLC.EUS-guided intraportal bone marrow injection was performed in all patients successfully without any complications such as hemorrhage.The clinical outcomes of the patients revealed improvements in clinical symptoms,serum albumin,ascites,and Child-Pugh scores throughout the 12-mo follow-up.CONCLUSION The use of EUS-guided fine needle injection for intraportal delivery of bone marrow was feasible and safe and appeared effective in patients with DLC.This treatment may thus be a safe,effective,non-radioactive,and minimally invasive treatment for DLC.展开更多
BACKGROUND The emergence of secondary drug resistance when treating epidermal growth factor receptor(EGFR)mutated non-small cell lung cancer(NSCLC)using EGFRtyrosine kinase inhibitors(EGFR-TKIs),seriously affects the ...BACKGROUND The emergence of secondary drug resistance when treating epidermal growth factor receptor(EGFR)mutated non-small cell lung cancer(NSCLC)using EGFRtyrosine kinase inhibitors(EGFR-TKIs),seriously affects the therapeutic efficacy and survival of patients.Here,we report a case of advanced NSCLC focusing on the application of multiple biopsy modalities to reveal the development of multiple resistance mechanisms during targeted therapies.CASE SUMMARY A 54-year-old male patient presented with EGFR 19Del-mutated advanced lung adenocarcinoma,and exhibited the development of a T790M mutation during initial TKI treatment.Following 3 mo of Osimertinib treatment,a mixed response was observed.Tissue biopsy of the progressive lesion showed transformation to small cell lung cancer(SCLC)harboring RB1 and TP53 mutations,with loss of the original T790M mutation.A standard chemotherapy regimen with Anlotinib for SCLC was administered.Repeat biopsy revealed adenocarcinoma combined with SCLC after tumor progression.The patient’s overall survival was 24 mo.CONCLUSION Multiple biopsy modalities can reveal the development of multiple resistance mechanisms which help with treatment decision-making.Comprehensive treatment regimens according to the drug resistance mechanism significantly improved the prognosis of such patients.展开更多
Drought and low temperature are two key environmental factors that induce adult citrus flowering. However, the underlying regulation mechanism is poorly understood. The bZIP transcription factor FD is a key component ...Drought and low temperature are two key environmental factors that induce adult citrus flowering. However, the underlying regulation mechanism is poorly understood. The bZIP transcription factor FD is a key component of the florigen activation complex(FAC) which is composed of FLOWERING LOCUS T(FT), FD, and 14-3-3 proteins. In this study, isolation and characterization of CiFD in citrus found that there was alternative splicing(AS) of CiFD, forming two different proteins(CiFDα and CiFDβ). Further investigation found that their expression patterns were similar in different tissues of citrus, but the subcellular localization and transcriptional activity were different. Overexpression of the CiFD DNA sequence(CiFD-DNA), CiFDα, or CiFDβ in tobacco and citrus showed early flowering, and CiFD-DNA transgenic plants were the earliest, followed by CiFDβ and CiFDα. Interestingly, CiFDα and CiFDβ were induced by low temperature and drought, respectively. Further analysis showed that CiFDαcan form a FAC complex with CiFT, Ci14-3-3, and then bind to the citrus APETALA1(CiAP1) promoter and promote its expression. However,CiFDβ can directly bind to the CiAP1 promoter independently of CiFT and Ci14-3-3. These results showed that CiFDβ can form a more direct and simplified pathway that is independent of the FAC complex to regulate drought-induced flowering through AS. In addition, a b HLH transcription factor(CibHLH96) binds to CiFD promoter and promotes the expression of CiFD under drought condition. Transgenic analysis found that CibHLH96 can promote flowering in transgenic tobacco. These results suggest that CiFD is involved in drought-and low-temperature-induced citrus flowering through different regulatory patterns.展开更多
In this study,27 new sesquiterpenoids:twenty monomers and seven dimers,with diverse structures,along with one known chlora-japonilide F(25)were isolated from the aerial parts of Chloranthus henryi var.hupehensis.Struc...In this study,27 new sesquiterpenoids:twenty monomers and seven dimers,with diverse structures,along with one known chlora-japonilide F(25)were isolated from the aerial parts of Chloranthus henryi var.hupehensis.Structurally,chlorahupetolides A(1)and B(2),two eudesmane-type merosesquiterpenoids with an undescribed C18 carbon framework,and chlorahupetene E(18)are the first example of dimers comprising two eudesmane sesquiterpenoids bridged by a four-membered ring in the Chloranthus.Their struc-tures were characterized by nuclear magnetic resonance(NMR),electronic circular dichroism(ECD),and X-ray diffraction analysis.In the RAW264.7 macrophages model of inflammation induced by LPS,compounds 12,18,and 25 significantly reduced NO production in a dose dependent manner and without cytotoxicity.The mRNA expression of COX-2 was considerably inhibited by treatments with compounds 12,18,and 25.展开更多
Hydrogen sulfide (H_(2)S) is one of the three known gas signal transducers, and since its potential physiological role was reported, the literature on H_(2)S has been increasing. H_(2)S is involved in processes such a...Hydrogen sulfide (H_(2)S) is one of the three known gas signal transducers, and since its potential physiological role was reported, the literature on H_(2)S has been increasing. H_(2)S is involved in processes such as vasodilation, neurotransmission, angiogenesis, inflammation, and the prevention of ischemia-reperfusion injury, and its mechanism remains to be further studied. At present, the role of post-translational processing of proteins has been considered as a possible mechanism for the involvement of H_(2)S in a variety of physiological processes. Current studies have shown that H_(2)S is involved in S-sulfhydration, phosphorylation, and S-nitrosylation of proteins, etc. This paper focuses on the effects of protein modification involving H_(2)S on physiological and pathological processes, looking forward to providing guidance for subsequent research.展开更多
The hypothalamic paraventricular nucleus(PVN) is a crucial region involved in maintaining homeostasis through the regulation of cardiovascular, neuroendocrine, and other functions. The PVN provides a dominant source o...The hypothalamic paraventricular nucleus(PVN) is a crucial region involved in maintaining homeostasis through the regulation of cardiovascular, neuroendocrine, and other functions. The PVN provides a dominant source of excitatory drive to the sympathetic outflow through innervation of the brainstem and spinal cord in hypertension. We discuss current findings on the role of the PVN in the regulation of sympathetic output in both normotensive and hypertensive conditions. The PVN seems to play a major role in generating the elevated sympathetic vasomotor activity that is characteristic of multiple forms of hypertension, including primary hypertension in humans. Recent studies in the spontaneously hypertensive rat model have revealed an imbalance of inhibitory and excitatory synaptic inputs to PVN presympathetic neurons as indicated by impaired inhibitory and enhanced excitatory synaptic inputs in hypertension.This imbalance of inhibitory and excitatory synaptic inputs in the PVN forms the basis for elevated sympathetic outflow in hypertension. In this review, we discuss the disruption of balance between glutamatergic and GABAergic inputs and the associated cellular and molecular alterations as mechanisms underlying the hyperactivity of PVN pre-sympathetic neurons in hypertension.展开更多
Pollen germination and embryogenesis are important to sexual plant reproduction. The processes require a large number of genes to be expressed. Transcription of eukaryotic nuclear genes is accomplished by three conser...Pollen germination and embryogenesis are important to sexual plant reproduction. The processes require a large number of genes to be expressed. Transcription of eukaryotic nuclear genes is accomplished by three conserved RNA polymerases acting in association with a set of auxiliary general transcription factors （GTFs）, including B-type GTFs. The roles of B-type GTFs in plant reproduction remain poorly understood. Here we report functional characterization of a novel plant-specific TFIIB-related gene PTF2 in Arabidopsis. Mutation in PTF2 caused failure of pollen germination. Pollen-rescue revealed that the mutation also disrupted embryogenesis and resulted in seed abortion. PTF2 is expressed prolifically in developing pollen and the other tissues with active cell division and differentiation, including embryo and shoot apical meristem. The PTF2 protein shares a lower amino acid sequence similarity with other known TFIIB and TFIIB-related proteins in Arabidopsis. It can interact with TATA-box binding protein 2 （TBP2） and bind to the double- stranded DNA （dsDNA） as the other known TFIIB and TFIIB-related proteins do. In addition, PTF2 can form a homodimer and interact with the subunits of RNA polymerases （RNAPs）, implying that it may be involved in the RNAPs transcription. These results suggest that PTF2 plays crucial roles in pollen germination and embryogenesis in Arabidopsis, possibly by regulating gene expression through interaction with TBP2 and the subunits of RNAPs.展开更多
Neonatal sepsis is common in neonatal intensive care units, often complicated by injury to the immature brain. Previous studies have shown that the expression of the gap junction protein connexin 43 （Cx43） in the br...Neonatal sepsis is common in neonatal intensive care units, often complicated by injury to the immature brain. Previous studies have shown that the expression of the gap junction protein connexin 43 （Cx43） in the brain decreases when stimulated by neuro-inflammatory drugs such as lipopolysaccharide （LPS）. Here we showed that partial deletion of Cx43 in astrocytes resulted in weakened inflammatory responses. The up-regulation of pro-inflammatory cytokines was significantly reduced in mice with partial deletion of Cx43 in astrocytes compared with wild-type littermates after systemic LPS injection. Moreover, microglial activation was inhibited in mice with partial deletion of Cx43. These results showed that Cx43 in astrocytes plays a critical role in neuro-inflammatory responses. This work provides a potential therapeutic target for inhibiting neuro- inflammatory responses in neonatal sepsis.展开更多
文摘BACKGROUND Gastrointestinal symptoms are common in patients with uremia undergoing hemodialysis,and these symptoms seriously affect patients'prognosis.AIM To assess the occurrence and factors influencing gastrointestinal symptoms in patients with uremia undergoing hemodialysis.METHODS We retrospectively selected 98 patients with uremia who underwent regular hemo-dialysis treatment in the blood purification center of our hospital from December 2022 to December 2023.The gastrointestinal symptoms and scores of each dimension were evaluated using the Gastrointestinal Symptom Grading Scale(GSRS).Patients were divided into gastrointestinal symptoms and no gastrointestinal symptom groups according to whether they had gastrointestinal symptoms.The factors that may affect gastrointestinal symptoms were identified by single-factor analysis.Multiple logistic regression analysis was performed to identify independent risk factors for gastrointestinal symptoms.RESULTS Gastrointestinal symptoms included indigestion,constipation,reflux,diarrhea,abdominal pain,and eating disorders,and the total average GSRS score was 1.35±0.47.This study showed that age,number of tablets,dialysis time,glucocorticoid,parathyroid hormone(PTH),combined diabetes mellitus and C-reactive protein(CRP)were independent risk factors for gastrointestinal symptoms in patients with uremia undergoing hemodialysis,whereas body mass index(BMI),hemoglobin(Hb),and urea clearance index were independent protective factors(P<0.05).CONCLUSION Gastrointestinal symptoms are mostly mild in patients with uremia undergoing hemodialysis,most commonly including dyspepsia,eating disorders,and gastroesophageal reflux.The independent influencing factors mainly include the BMI,age,number of pills taken,dialysis time,urea clearance index,Hb,use of glucocorticoids,and thyroid hormone level.PTH,CRP,and diabetes are clinically related factors influencing the occurrence of gastrointestinal symptoms,and targeted prevention can be performed.
基金Supported by the National Natural Science Foundation of China,No. 82270594National Natural Science Foundation for Youths of China,No. 882002614 and No. 82103151+4 种基金Hunan Provincial Natural Science Foundation of China,No. 2020JJ4853Scientific Research Project of Hunan Provincial Health Commission,No. 202103032097Outstanding Youth Foundation of Hunan Province,No. 2022JJ20092Hunan Provincial Natural Science Foundation of China for Youths,No. 2021JJ40935 and No. 2020JJ5609Wisdom Accumulation and Talent Cultivation Project of Third Xiangya Hospital of Central South University,No. YX202103
文摘BACKGROUND Recently,stem cell therapy has been extensively studied as a promising treatment for decompensated liver cirrhosis(DLC).Technological advances in endoscopic ultrasonography(EUS)have facilitated EUS-guided portal vein(PV)access,through which stem cells can be precisely infused.AIM To investigate the feasibility and safety of fresh autologous bone marrow injection into the PV under EUS guidance in patients with DLC.METHODS Five patients with DLC were enrolled in this study after they provided written informed consent.EUS-guided intraportal bone marrow injection with a 22G FNA needle was performed using a transgastric,transhepatic approach.Several parameters were assessed before and after the procedure for a follow-up period of 12 mo.RESULTS Four males and one female with a mean age of 51 years old participated in this study.All patients had hepatitis B virus-related DLC.EUS-guided intraportal bone marrow injection was performed in all patients successfully without any complications such as hemorrhage.The clinical outcomes of the patients revealed improvements in clinical symptoms,serum albumin,ascites,and Child-Pugh scores throughout the 12-mo follow-up.CONCLUSION The use of EUS-guided fine needle injection for intraportal delivery of bone marrow was feasible and safe and appeared effective in patients with DLC.This treatment may thus be a safe,effective,non-radioactive,and minimally invasive treatment for DLC.
文摘BACKGROUND The emergence of secondary drug resistance when treating epidermal growth factor receptor(EGFR)mutated non-small cell lung cancer(NSCLC)using EGFRtyrosine kinase inhibitors(EGFR-TKIs),seriously affects the therapeutic efficacy and survival of patients.Here,we report a case of advanced NSCLC focusing on the application of multiple biopsy modalities to reveal the development of multiple resistance mechanisms during targeted therapies.CASE SUMMARY A 54-year-old male patient presented with EGFR 19Del-mutated advanced lung adenocarcinoma,and exhibited the development of a T790M mutation during initial TKI treatment.Following 3 mo of Osimertinib treatment,a mixed response was observed.Tissue biopsy of the progressive lesion showed transformation to small cell lung cancer(SCLC)harboring RB1 and TP53 mutations,with loss of the original T790M mutation.A standard chemotherapy regimen with Anlotinib for SCLC was administered.Repeat biopsy revealed adenocarcinoma combined with SCLC after tumor progression.The patient’s overall survival was 24 mo.CONCLUSION Multiple biopsy modalities can reveal the development of multiple resistance mechanisms which help with treatment decision-making.Comprehensive treatment regimens according to the drug resistance mechanism significantly improved the prognosis of such patients.
基金supported financially by the National Major Research and Development Plan (2018YFD1000104)the National Natural Science Foundation of China (32072521, 31772252, 31901963, and 31872045)。
文摘Drought and low temperature are two key environmental factors that induce adult citrus flowering. However, the underlying regulation mechanism is poorly understood. The bZIP transcription factor FD is a key component of the florigen activation complex(FAC) which is composed of FLOWERING LOCUS T(FT), FD, and 14-3-3 proteins. In this study, isolation and characterization of CiFD in citrus found that there was alternative splicing(AS) of CiFD, forming two different proteins(CiFDα and CiFDβ). Further investigation found that their expression patterns were similar in different tissues of citrus, but the subcellular localization and transcriptional activity were different. Overexpression of the CiFD DNA sequence(CiFD-DNA), CiFDα, or CiFDβ in tobacco and citrus showed early flowering, and CiFD-DNA transgenic plants were the earliest, followed by CiFDβ and CiFDα. Interestingly, CiFDα and CiFDβ were induced by low temperature and drought, respectively. Further analysis showed that CiFDαcan form a FAC complex with CiFT, Ci14-3-3, and then bind to the citrus APETALA1(CiAP1) promoter and promote its expression. However,CiFDβ can directly bind to the CiAP1 promoter independently of CiFT and Ci14-3-3. These results showed that CiFDβ can form a more direct and simplified pathway that is independent of the FAC complex to regulate drought-induced flowering through AS. In addition, a b HLH transcription factor(CibHLH96) binds to CiFD promoter and promotes the expression of CiFD under drought condition. Transgenic analysis found that CibHLH96 can promote flowering in transgenic tobacco. These results suggest that CiFD is involved in drought-and low-temperature-induced citrus flowering through different regulatory patterns.
基金supported by grants from the Natural Science Foundation of Hebei Province(Program No.H2022209046)Nanjing Special Fund of Traditional Chinese Medicine(Program No.ZYYB202203)the Natural Science Foundation of Hebei Province(Program No.H2022209053).
文摘In this study,27 new sesquiterpenoids:twenty monomers and seven dimers,with diverse structures,along with one known chlora-japonilide F(25)were isolated from the aerial parts of Chloranthus henryi var.hupehensis.Structurally,chlorahupetolides A(1)and B(2),two eudesmane-type merosesquiterpenoids with an undescribed C18 carbon framework,and chlorahupetene E(18)are the first example of dimers comprising two eudesmane sesquiterpenoids bridged by a four-membered ring in the Chloranthus.Their struc-tures were characterized by nuclear magnetic resonance(NMR),electronic circular dichroism(ECD),and X-ray diffraction analysis.In the RAW264.7 macrophages model of inflammation induced by LPS,compounds 12,18,and 25 significantly reduced NO production in a dose dependent manner and without cytotoxicity.The mRNA expression of COX-2 was considerably inhibited by treatments with compounds 12,18,and 25.
基金supported by grants from the National Natural Science Foundation of China(No.81802718 and 81670088)the Training Program for Young Backbone Teachers of Institutions of Higher Learning in Henan Province,China(No.2020GGJS038)the Foundation of Science&Technology Department of Henan Province,China(No.202102310480,222102310490,and 222102310495).
文摘Hydrogen sulfide (H_(2)S) is one of the three known gas signal transducers, and since its potential physiological role was reported, the literature on H_(2)S has been increasing. H_(2)S is involved in processes such as vasodilation, neurotransmission, angiogenesis, inflammation, and the prevention of ischemia-reperfusion injury, and its mechanism remains to be further studied. At present, the role of post-translational processing of proteins has been considered as a possible mechanism for the involvement of H_(2)S in a variety of physiological processes. Current studies have shown that H_(2)S is involved in S-sulfhydration, phosphorylation, and S-nitrosylation of proteins, etc. This paper focuses on the effects of protein modification involving H_(2)S on physiological and pathological processes, looking forward to providing guidance for subsequent research.
基金supported by National Institutes of Health Grants HL131161,HL139523,and HL142133
文摘The hypothalamic paraventricular nucleus(PVN) is a crucial region involved in maintaining homeostasis through the regulation of cardiovascular, neuroendocrine, and other functions. The PVN provides a dominant source of excitatory drive to the sympathetic outflow through innervation of the brainstem and spinal cord in hypertension. We discuss current findings on the role of the PVN in the regulation of sympathetic output in both normotensive and hypertensive conditions. The PVN seems to play a major role in generating the elevated sympathetic vasomotor activity that is characteristic of multiple forms of hypertension, including primary hypertension in humans. Recent studies in the spontaneously hypertensive rat model have revealed an imbalance of inhibitory and excitatory synaptic inputs to PVN presympathetic neurons as indicated by impaired inhibitory and enhanced excitatory synaptic inputs in hypertension.This imbalance of inhibitory and excitatory synaptic inputs in the PVN forms the basis for elevated sympathetic outflow in hypertension. In this review, we discuss the disruption of balance between glutamatergic and GABAergic inputs and the associated cellular and molecular alterations as mechanisms underlying the hyperactivity of PVN pre-sympathetic neurons in hypertension.
基金the research grants from the Ministry of Sciences and Technology，the Natural Science Foundation of China，the Ministry of Education
文摘Pollen germination and embryogenesis are important to sexual plant reproduction. The processes require a large number of genes to be expressed. Transcription of eukaryotic nuclear genes is accomplished by three conserved RNA polymerases acting in association with a set of auxiliary general transcription factors （GTFs）, including B-type GTFs. The roles of B-type GTFs in plant reproduction remain poorly understood. Here we report functional characterization of a novel plant-specific TFIIB-related gene PTF2 in Arabidopsis. Mutation in PTF2 caused failure of pollen germination. Pollen-rescue revealed that the mutation also disrupted embryogenesis and resulted in seed abortion. PTF2 is expressed prolifically in developing pollen and the other tissues with active cell division and differentiation, including embryo and shoot apical meristem. The PTF2 protein shares a lower amino acid sequence similarity with other known TFIIB and TFIIB-related proteins in Arabidopsis. It can interact with TATA-box binding protein 2 （TBP2） and bind to the double- stranded DNA （dsDNA） as the other known TFIIB and TFIIB-related proteins do. In addition, PTF2 can form a homodimer and interact with the subunits of RNA polymerases （RNAPs）, implying that it may be involved in the RNAPs transcription. These results suggest that PTF2 plays crucial roles in pollen germination and embryogenesis in Arabidopsis, possibly by regulating gene expression through interaction with TBP2 and the subunits of RNAPs.
基金supported by the National Science Foundation of China (81171148)Shanghai Natural Science Foundation (10411960700)
文摘Neonatal sepsis is common in neonatal intensive care units, often complicated by injury to the immature brain. Previous studies have shown that the expression of the gap junction protein connexin 43 （Cx43） in the brain decreases when stimulated by neuro-inflammatory drugs such as lipopolysaccharide （LPS）. Here we showed that partial deletion of Cx43 in astrocytes resulted in weakened inflammatory responses. The up-regulation of pro-inflammatory cytokines was significantly reduced in mice with partial deletion of Cx43 in astrocytes compared with wild-type littermates after systemic LPS injection. Moreover, microglial activation was inhibited in mice with partial deletion of Cx43. These results showed that Cx43 in astrocytes plays a critical role in neuro-inflammatory responses. This work provides a potential therapeutic target for inhibiting neuro- inflammatory responses in neonatal sepsis.
