Background: Primary pulmonary angiosarcoma is extremely rare and the prognosis is very poor. We report a combination therapy of pneumonectomy and intrapleural hypotonic hyperthermic chemotherapy (IPHHC). Case report: ...Background: Primary pulmonary angiosarcoma is extremely rare and the prognosis is very poor. We report a combination therapy of pneumonectomy and intrapleural hypotonic hyperthermic chemotherapy (IPHHC). Case report: A 48-year-old male with exertional dyspnea was found to have a left massive pleural effusion. Bronchoscopic examination displayed endobronchial stenosis of the left lower bronchus B8,9,10?and diagnosed with pulmonary angiosarcoma. Chest computed-tomographic scanning revealed a 5-cm mass in the left inferior lobe, which invaded the left upperbronchus. Intrapleural dissemination and malignant pleural effusion were also suspected (cT3N1M1a,?c-stage IV). As a palliative initial therapy, we performed a pneumonectomy. On the 7th?postoperative day, under general anesthesia, we performed video-assisted IPHHC (43°C, 60 min, 200 mg/m2?of CDDP). After the IPHHC, there was no major adverse event (more than Grade 3) during the postoperative course. Histological examination of the resected specimen revealed a highly-cellular growth of atypical spindle cells with a storiform pattern. By immunohistochemical testing, the tumor cells stained positive for markers including CD31 and the factor VIII related antigen, and the diagnosis of pulmonary angiosarcoma was made. No adjuvant chemoradiotherapy was given, and the postoperative clinical course was uneventful. Although there had been a recurrence in the chest wall, the patient eventually died twenty-one months later. Conclusion: As a new therapeutic option, we performed IPHHC after the pneumonectomy for an advanced pulmonary angiosarcoma with malignant pleural effusion. Although the patient had a recurrence in the chest wall, he had a reasonable postoperative outcome, that is, he returned to a work, retained a good quality of life and had a longer survival in spite of the poor prognosis of the pulmonary angiosarcoma.展开更多
BACKGROUND： Aquaporin-4 （AQP4） is abundant in astrocytes, ependymal cells, and the choroid plexus, and is associated with cerebrospinal fluid formation and osmoregulation. AQP4 is speculated to be the hypothalamic ...BACKGROUND： Aquaporin-4 （AQP4） is abundant in astrocytes, ependymal cells, and the choroid plexus, and is associated with cerebrospinal fluid formation and osmoregulation. AQP4 is speculated to be the hypothalamic osmoreceptor and regulator of water balance. OBJECTIVE： To examine AQP4 expression and its role in cultured rat astrocytes after exposure to hypotonic medium. DESIGN, TIME AND SETTING： Randomized control experiment. This experiment was carried out in the Research Room of Neurobiology, Chongqing University of Medical Science, China, between April and October 2003. MATERIALS： Two-day-old newborn Wistar rats （n =20）, weighing 10- 15 g, were purchased from the Experimental Animal Center of Chongqing University of Medical Science, China. METHODS： Purified rat cerebral cortical astrocytes were isolated fiom Wistar rats for in vitro cell culture experiments. The cells were randomly divided into control and hypotonic groups. The in vitro cell edema model was established by exposing astrocytes to hypotonic medium （268, 254, or 240 mmol/L）. Cells in the control group were cultured in normal culture medium. MAIN OUTCOME MEASURES： Morphological changes in astrocytes were observed under an inverted microscope and a transmission electron microscope after cells were cultured for 3, 6, 12, or 24 hours with hypotonic medium or normal culture medium. In each group, AQP4 protein and mRNA expression were assessed by immunocytochemistry, in situ hybridization, and reverse transcription polymerase chain reaction at the different time points. RESULTS： After astrocytes were cultured for 3, 6, 12, or 24 hours with hypotonic medium （268, 254, 240 mmol/L）, they showed typical features of cell edema. In the control group, no astrocytes developed pathological changes. There were no significant changes in the AQP4 mRNA and protein expression in the control group at any of the time points alter astrocytes were cultured with normal culture medium （P 〉 0.05）. Compared with the control group, AQP4 mRNA and protein expression in the hypotonic group were remarkably increased at all time points after astrocytes cultured with hypotonic medium （268, 254, 240 mmol/L; P 〈 0.05）. AQP4 mRNA and protein expression increased with increasing exposure time and with decreasing concentration of the hypotonic medium. CONCLUSION： Hypotonic medium induced cell edema and increased AQP4 mRNA and protein expression. Up-regulated expression of AQP4 was correlated with hypotonic medium concentration in a time dependent manner.展开更多
Using theoretical analysis, the single-phase gas seepage mathematical model influenced by slippage effects was established. The results show that the pressure of producing wells attenuates more violently than the well...Using theoretical analysis, the single-phase gas seepage mathematical model influenced by slippage effects was established. The results show that the pressure of producing wells attenuates more violently than the wells without slippage effects. The decay rate of reservoir pressure is more violent as the Klinkenherg factor increases. The gas prediction output gradually increases as the Klinenberg factor increases when considering gas slippage effects. Through specific examples, analyzed the law of stope pore pressure and gas output forecast changing in a hypotonic reservoir with slippage effects. The results have great theoretical significance in the study of the law of coal-bed methane migration in hypotonic reservoirs and for the exploitation of coal-bed methane.展开更多
Cell-based assays represent a major end point of high throughput screening (HTS) but a key limitation of such assays is the potentially poor membrane permeability of test compounds. In this study, we optimized the con...Cell-based assays represent a major end point of high throughput screening (HTS) but a key limitation of such assays is the potentially poor membrane permeability of test compounds. In this study, we optimized the conditions for the delivery of the membrane impermeable compound 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) into human cells using hypotonic shift;a method that can promote the uptake of molecules from the extracellular fluid into cell cytoplasm via endocytosis. We showed that uptake of HPTS by cells was a function of hypotonic buffer osmolarity and that delivery was highly efficient with almost 100% of cells displaying uptake. Delivery of HPTS was equally effective at 25°C and 37°C, with delivery of compound proportional to incubation time and concentration of HPTS within the loading medium. The experimental conditions identified in this study could be applied to HTS drug discovery studies providing an effective method of delivering small membrane impermeable compounds into cells.展开更多
Background The incidence of contrast induced nephropathy （CIN） is increasing while patients are more and more frequently undertaking coronary angiography and percutaneous coronary intervention （PCI）. CIN correlate...Background The incidence of contrast induced nephropathy （CIN） is increasing while patients are more and more frequently undertaking coronary angiography and percutaneous coronary intervention （PCI）. CIN correlates with the later cardiovascular events, the rising mortality risks and the increasing one-year target vessel revascularization. At present, few articles reported on whether the incidence of CIN induced by isotonic and hypotonic contrast agent after PCI is different or not. Objectives To investigate the different effect of isotonic and hypotonic contrast agent in inducing CIN in patients with coronary artery disease after PCI. Methods We enrolled 355 patients with coronary artery disease who undertook PCI from January 2007 to December 2008 as subjects. Renal functions of all 355 patients were normal. Patients were randomly divided into isotonic group and hypotonic group. Concentrations of serum creatinine （SCr） were measured before, 48～72 hours and 7 days （if needed） after PCI. The glomerular filtration rate （eGFR） was calculated according to MDRD formula. The incidence of CIN was defined as the concentration of SCr ≥0.5 mg/dL（44.2 μmol/L）. Hemodialysis rates and mortality were recorded in the hospital. Results There was no significant difference in the basline eGFR （79.52±5.28 vs 81.03±6.09, P0.05）, dosages of contrast agent （125.68±15.88 mL vs 123.51±16.38 mL, P0.05）, eGFR of 48-72 hours after PCI （70.26±9.48 vs 69.06±9.59, P0.05） and incidences of CIN （5.56% vs 5.78%, P0.05） between the two groups. eGFR and concentrations of SCr 7 days after PCI showed no significant difference between the two groups （P0.05）. No patient was dead or needed hemodialysis in hospital. Conclusions The effect of isotonic and hypotonic contrast agent in inducing CIN in patients with coronary artery disease after PCI has no difference.展开更多
Objective: To observe the time of ascites disappearance, time to ascites recurrence, improvement rate in quality of life, and the effective rate of ascites treatment in patients with advanced gastric and ovarian cance...Objective: To observe the time of ascites disappearance, time to ascites recurrence, improvement rate in quality of life, and the effective rate of ascites treatment in patients with advanced gastric and ovarian cancer with ascites following hypotonic hyperthermic intraperitoneal chemotherapy. Methods: Forty patients with advanced gastric and ovarian cancer with ascites, treated in our hospital from January 2021 to August 2024, were selected as research subjects. They were divided into a treatment group and a reference group using a random number table method. The treatment group received hypotonic hyperthermic intraperitoneal chemotherapy, while the reference group received conventional treatment. The treatment effects of the two groups were compared. Results: In the treatment group, the ascite disappearance time was (6.13 ± 1.32) days, and the recurrence time was (22.58 ± 8.21) months. The ascite disappearance time was significantly shorter than that of the reference group, and the ascite recurrence time was significantly longer. Both P-values were less than 0.05, indicating statistical significance. The effective rate of quality of life improvement was 95%, with only 1 patient showing a decrease in quality of life. The effective rate of ascites treatment was 95%, with only 1 patient showing an increase in ascites. Both the quality of life improvement rate and the effective rate of ascites treatment were significantly higher than those of the reference group, with P-values of 0.037 and 0.018, respectively, indicating statistical significance. Conclusion: For patients with advanced gastric and ovarian cancer with ascites, hypotonic hyperthermic intraperitoneal chemotherapy can accelerate ascites disappearance, prolong the time to recurrence, and significantly improve both the quality of life improvement rate and the effective rate of ascites treatment.展开更多
Red blood cells(RBCs)can act as carriers for therapeutic agents and can substantially improve the safety,pharmacokinetics,and pharmacodynamics of many drugs.Maintaining RBCs integrity and lifespan is important for the...Red blood cells(RBCs)can act as carriers for therapeutic agents and can substantially improve the safety,pharmacokinetics,and pharmacodynamics of many drugs.Maintaining RBCs integrity and lifespan is important for the efficacy of RBCs as drug carrier.We investigated the impact of drug encapsulation by hypotonic dialysis on RBCs physiology and integrity.Several parameters were compared between processed RBCs loaded with l-asparaginase(“eryaspase”),processed RBCs without drug and non-processed RBCs.Processed RBCs were less hydrated and displayed a reduction of intracellular content.We observed a change in the metabolomic but not in the proteomic profile of processed RBCs.Encapsulation process caused moderate morphological changes and was accompanied by an increase of RBCs-derived Extracellular Vesicles release.Despite a decrease in deformability,processed RBCs were not mechanically retained in a spleen-mimicking device and had increased surface-to-volume ratio and osmotic resistance.Processed RBCs half-life was not significantly affected in a mouse model and our previous phase 1 clinical study showed that encapsulation of asparaginase in RBCs prolonged its in vivo half-life compared to free forms.Our study demonstrated that encapsulation by hypotonic dialysis may affect certain characteristics of RBCs but does not significantly affect the in vivo longevity of RBCs or their drug carrier function.展开更多
The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water(TBW) and total effective solute and is ...The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water(TBW) and total effective solute and is expressed in terms of the tonicity of the body fluids. Disturbances in tonicity are the main factor responsible for changes in cell volume, which can critically affect brain cell function and survival. Solutes distributed almost exclusively in the extracellular compartment(mainly sodium salts) and in the intracellular compartment(mainly potassium salts) contribute to tonicity, while solutes distributed in TBW have no effect on tonicity. The second body fluid balance concept relates to the regulation and measurement of abnormalities of sodium salt balance and extracellular volume. Estimation of extracellular volume is more complex and error prone than measurement of TBW. A key function of extracellular volume, which is defined as the effective arterial blood volume(EABV), is to ensure adequate perfusion of cells and organs. Other factors, including cardiac output, total and regional capacity of both arteries and veins, Starling forces in the capillaries, and gravity also affect the EABV. Collectively, these factors interact closely with extracellular volume and some of them undergo substantial changes in certain acute and chronic severe illnesses. Their changes result not only in extracellular volume expansion, but in the need for a larger extracellular volume compared with that of healthy individuals. Assessing extracellular volume in severe illness is challenging because the estimates of this volume by commonly used methods are prone to large errors in many illnesses. In addition, the optimal extracellular volume may vary from illness to illness, is only partially based on volume measurements by traditional methods, and has not been determined for each illness. Further research is needed to determine optimal extracellular volume levels in several illnesses. For these reasons, extracellular volume in severe illness merits a separate third concept of body fluid balance.展开更多
Objective: It has been suggested that the use of hypotonic intravenous fluid (IVF) puts hospitalized children at a greater risk of developing hyponatremia in children with increased arginine vasopressin (AVP) producti...Objective: It has been suggested that the use of hypotonic intravenous fluid (IVF) puts hospitalized children at a greater risk of developing hyponatremia in children with increased arginine vasopressin (AVP) production. To reduce its risk, the National Patient Safety Agency in UK issued alert 22 in 2007, of which recommendations were to use isotonic solutions for these children at risk of hyponatremia, instead of the previously most commonly used IVF (0.18% saline/ 4% dextrose) for maintenance fluid therapy. Recent observations, however, revealed that hypokalemia are also common in hospitalized patients who do not receive potassium in their IVF. This study was conducted to validate the potassium added IVF for the prevention of hospital-acquired hypokalemia in maintenance fluid therapy. Design: For maintenance fluid therapy, a commercially available IVF solution in Japan named as Solita-T2R (Na 84 mmol/L, K 20 mmol/L, Cl 66 mmol/L, glucose 3.2%) was infused for 41 sick children with a median age of 3.01 years. Its composition is close equivalent to 0.45% saline/5% dextrose (Na 77 mmol/L, K 0 mmol/L, Cl 77 mmol/L, dextrose 5%) except K content. The patients in states of AVP excess were excluded from the analysis. Results: Median serum potassium value did not drop significantly at a median interval of 48 hours (before IVF: 4.30 mmol/L, after IVF: 4.10 mmol/L, p > 0.05), whereas median serum sodium level significantly increased from 136.0 mmol/L to 139.0 mmol/L (p < 0.001). Conclusion: Potassium added (20 mmol/L) IVF solution reduces the risk of developing “hospital-acquired hypokalemia” in children who are not in states of AVP excess in maintenance fluid therapy. It is worthwhile to study prospectively in a larger number of sick children.展开更多
Introduction: Intracellular calcium concentration ([Ca2+]i) is a critical parameter in cellular homeostasis, including articular chondrocytes. Perturbed [Ca2+]i of chondrocytes may be associated with joint disease. Th...Introduction: Intracellular calcium concentration ([Ca2+]i) is a critical parameter in cellular homeostasis, including articular chondrocytes. Perturbed [Ca2+]i of chondrocytes may be associated with joint disease. The objective of the study was to compare large animal models for investigating Ca2+ homeostasis in chondrocytes. Materials and Methods: The gross anatomy of the metacarpophalangeal joint (MCP) of cattle and sheep was compared, along with the effect of various manoeuvres used to study the mechanisms of Ca2+ homeostasis in chondrocytes from load-bearing areas. The gross anatomy was observed before and after dissection, and internal architecture was examined after sectioning. Cartilage thickness was measured with a digital micrometer. Chondrocyte yield was determined after isolation. Chondrocytes were incubated with Fura-2 and Ca2+i followed in different extracellular conditions. A hypotonic shock (HTS) was used to mimic removal of a load. Results: The results showed that ovids and bovids were skeletally immature and aspects of Ca2+ homeostasis were similar. Ovine chondrocytes had higher resting fluorescence, consistent with elevated resting Ca2+ levels. Results from ion substitution experiments were consistent with a role for Na+/Ca2+ exchange, and swelling-induced Ca2+ enters into the cytoplasm via the plasma membrane and intracellular stores. Conclusions: Ca2+ homeostasis in chondrocytes from both species behaved in a similar manner to HTS and ion substitutions. Differences in resting [Ca2+]i could be associated with species, stage of maturation, or Fura-2 itself and require further investigation. These findings contribute to our understanding of the physiology of articular cartilage in different species, and their potential use as models for studying joint disease in humans.展开更多
NFAT5 plays a critical role in maintaining the renal functions. Its dis-regulation in the kidney leads to or is associated with certain renal diseases or disorders, most notably the urinary concentration defect. Hyper...NFAT5 plays a critical role in maintaining the renal functions. Its dis-regulation in the kidney leads to or is associated with certain renal diseases or disorders, most notably the urinary concentration defect. Hypertonicity, which the kidney medulla is normally exposed to,activates NFAT5 through phosphorylation of a signaling molecule or NFAT5 itself. Hypotonicity inhibits NFAT5 through a similar mechanism. More than a dozen of protein and lipid kinases have been identified to contribute to tonicity-dependent regulation of NFAT5. Hypertonicity activates NFAT5 by increasing its nuclear localization and transactivating activity in the early phase and protein abundance in the late phase. The known mechanism for inhibition of NFAT5 by hypotonicity is a decrease of nuclear NFAT5. The present article reviews the effect of each kinase on NFAT5 nuclear localization, transactivation and protein abundance, and the relationship among these kinases, if known. Cyclosporine A and tacrolimus suppress immune reactions by inhibiting the phosphatase calcineurin-dependent activation of NFAT1. It is hoped that this review would stimulate the interest to seek explanations from the NFAT5 regulatory pathways for certain clinical presentations and to explore novel therapeutic approaches based on the pathways. On the basic science front, this review raises two interesting questions. The first one is how these kinases can specifcally signal to NFAT5 in the context of hypertonicity or hypotonicity, because they also regulate other cellular activities and even opposite activities in some cases. The second one is why these many kinases, some of which might have redundant functions, are needed to regulate NFAT5 activity. This review reiterates the concept of signaling through cooperation. Cells need these kinases working in a coordinated way to provide the signaling specificity that is lacking in the individual one. Redundancy in regulation of NFAT5 is a critical strategy for cells to maintain robustness against hypertonic or hypotonic stress.展开更多
Elevated glucose metabolism triggers two primary processes that lead toβ-cell depolarization and insulin secretion:the closure of ATPsensitive K+channels via ATP-dependent mechanisms and the activation of mechanosens...Elevated glucose metabolism triggers two primary processes that lead toβ-cell depolarization and insulin secretion:the closure of ATPsensitive K+channels via ATP-dependent mechanisms and the activation of mechanosensitive channels(MSCs)due to cell swelling.However,the identity of these MSCs remains unclear.In this study,we found that TMEM63B is a stretch-activated cation channel(SAC)crucial for regulating insulin secretion in response to elevated glucose levels.TMEM63B is abundantly expressed inβ-cells,and its deletion impairs insulin secretion triggered by high glucose.High glucose levels typically increase Ca2+influx and firing frequency inβ-cells,a response largely eliminated when TMEM63B is deleted.Mechanistically,glucose metabolism induces cell swelling and activates TMEM63B,which,in turn,leads toβ-cell depolarization and insulin secretion.In conclusion,our findings demonstrate that TMEM63B is an SAC essential for regulating insulin secretion in response to elevated glucose levels.展开更多
Objective:To evaluate the effectiveness of the use of a modified Zhukovsky double(vaginal and uterine)balloon to improve the results of treatment in women with obstetric hemorrhage.Methods:We conducted an observationa...Objective:To evaluate the effectiveness of the use of a modified Zhukovsky double(vaginal and uterine)balloon to improve the results of treatment in women with obstetric hemorrhage.Methods:We conducted an observational controlled study including 701 puerperas,which were divided into two groups:The main group consisted of 508 women,who underwent a combined management,that is,traditional(transfusion of fresh frozen plasma,erythrocyte mass,uterotonics,hemostatic agents),surgical hemostasis in cases of caesarean section,and insertion of a double Zhukovsky balloon;while the comparison group included 193 patients,who were managed traditionally.The main group and the comparison group were divided into subgroups according to the main etiology of obstetric hemorrhage:ⅠA andⅠB-postpartum;ⅡA andⅡB-placenta accreta;ⅢA andⅢB-postpartum hysterectomy.Results:The most frequent causes of massive obstetric hemorrhage were atony of the uterus(39.2%),placenta previa(29.1%),and placental abruption(11.5%).Of the 508 balloon insertions,345(70.7%)were inserted for hemorrhage during cesarean section and 148(29.3%)for obstetric hemorrhage after spontaneous delivery.Among the obstetric hemorrhage at caesarean section,lower segment bleeding prevailed(78.1%),caused mainly by placenta previa,placenta accreta,placental abruption,polyhydramnios,and uterine scar defects.Combined management,including surgical hemostasis and insertion of vaginal and uterine balloon of Zhukovsky,reduced blood loss by 1.5 times and the number of hysterectomies by 6.72 times compared to controls.Conclusion:The use of a modified Zhukovsky double balloon in the management of obstetric hemorrhage may reduce the number of hysterectomies and the amount of blood loss.展开更多
文摘Background: Primary pulmonary angiosarcoma is extremely rare and the prognosis is very poor. We report a combination therapy of pneumonectomy and intrapleural hypotonic hyperthermic chemotherapy (IPHHC). Case report: A 48-year-old male with exertional dyspnea was found to have a left massive pleural effusion. Bronchoscopic examination displayed endobronchial stenosis of the left lower bronchus B8,9,10?and diagnosed with pulmonary angiosarcoma. Chest computed-tomographic scanning revealed a 5-cm mass in the left inferior lobe, which invaded the left upperbronchus. Intrapleural dissemination and malignant pleural effusion were also suspected (cT3N1M1a,?c-stage IV). As a palliative initial therapy, we performed a pneumonectomy. On the 7th?postoperative day, under general anesthesia, we performed video-assisted IPHHC (43°C, 60 min, 200 mg/m2?of CDDP). After the IPHHC, there was no major adverse event (more than Grade 3) during the postoperative course. Histological examination of the resected specimen revealed a highly-cellular growth of atypical spindle cells with a storiform pattern. By immunohistochemical testing, the tumor cells stained positive for markers including CD31 and the factor VIII related antigen, and the diagnosis of pulmonary angiosarcoma was made. No adjuvant chemoradiotherapy was given, and the postoperative clinical course was uneventful. Although there had been a recurrence in the chest wall, the patient eventually died twenty-one months later. Conclusion: As a new therapeutic option, we performed IPHHC after the pneumonectomy for an advanced pulmonary angiosarcoma with malignant pleural effusion. Although the patient had a recurrence in the chest wall, he had a reasonable postoperative outcome, that is, he returned to a work, retained a good quality of life and had a longer survival in spite of the poor prognosis of the pulmonary angiosarcoma.
基金the National Natural Science Foundation of China, No.30070247
文摘BACKGROUND： Aquaporin-4 （AQP4） is abundant in astrocytes, ependymal cells, and the choroid plexus, and is associated with cerebrospinal fluid formation and osmoregulation. AQP4 is speculated to be the hypothalamic osmoreceptor and regulator of water balance. OBJECTIVE： To examine AQP4 expression and its role in cultured rat astrocytes after exposure to hypotonic medium. DESIGN, TIME AND SETTING： Randomized control experiment. This experiment was carried out in the Research Room of Neurobiology, Chongqing University of Medical Science, China, between April and October 2003. MATERIALS： Two-day-old newborn Wistar rats （n =20）, weighing 10- 15 g, were purchased from the Experimental Animal Center of Chongqing University of Medical Science, China. METHODS： Purified rat cerebral cortical astrocytes were isolated fiom Wistar rats for in vitro cell culture experiments. The cells were randomly divided into control and hypotonic groups. The in vitro cell edema model was established by exposing astrocytes to hypotonic medium （268, 254, or 240 mmol/L）. Cells in the control group were cultured in normal culture medium. MAIN OUTCOME MEASURES： Morphological changes in astrocytes were observed under an inverted microscope and a transmission electron microscope after cells were cultured for 3, 6, 12, or 24 hours with hypotonic medium or normal culture medium. In each group, AQP4 protein and mRNA expression were assessed by immunocytochemistry, in situ hybridization, and reverse transcription polymerase chain reaction at the different time points. RESULTS： After astrocytes were cultured for 3, 6, 12, or 24 hours with hypotonic medium （268, 254, 240 mmol/L）, they showed typical features of cell edema. In the control group, no astrocytes developed pathological changes. There were no significant changes in the AQP4 mRNA and protein expression in the control group at any of the time points alter astrocytes were cultured with normal culture medium （P 〉 0.05）. Compared with the control group, AQP4 mRNA and protein expression in the hypotonic group were remarkably increased at all time points after astrocytes cultured with hypotonic medium （268, 254, 240 mmol/L; P 〈 0.05）. AQP4 mRNA and protein expression increased with increasing exposure time and with decreasing concentration of the hypotonic medium. CONCLUSION： Hypotonic medium induced cell edema and increased AQP4 mRNA and protein expression. Up-regulated expression of AQP4 was correlated with hypotonic medium concentration in a time dependent manner.
基金Supported by the Youth Program of the National Natural Science Foundation of China （51004061）
文摘Using theoretical analysis, the single-phase gas seepage mathematical model influenced by slippage effects was established. The results show that the pressure of producing wells attenuates more violently than the wells without slippage effects. The decay rate of reservoir pressure is more violent as the Klinkenherg factor increases. The gas prediction output gradually increases as the Klinenberg factor increases when considering gas slippage effects. Through specific examples, analyzed the law of stope pore pressure and gas output forecast changing in a hypotonic reservoir with slippage effects. The results have great theoretical significance in the study of the law of coal-bed methane migration in hypotonic reservoirs and for the exploitation of coal-bed methane.
文摘Cell-based assays represent a major end point of high throughput screening (HTS) but a key limitation of such assays is the potentially poor membrane permeability of test compounds. In this study, we optimized the conditions for the delivery of the membrane impermeable compound 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) into human cells using hypotonic shift;a method that can promote the uptake of molecules from the extracellular fluid into cell cytoplasm via endocytosis. We showed that uptake of HPTS by cells was a function of hypotonic buffer osmolarity and that delivery was highly efficient with almost 100% of cells displaying uptake. Delivery of HPTS was equally effective at 25°C and 37°C, with delivery of compound proportional to incubation time and concentration of HPTS within the loading medium. The experimental conditions identified in this study could be applied to HTS drug discovery studies providing an effective method of delivering small membrane impermeable compounds into cells.
文摘Background The incidence of contrast induced nephropathy （CIN） is increasing while patients are more and more frequently undertaking coronary angiography and percutaneous coronary intervention （PCI）. CIN correlates with the later cardiovascular events, the rising mortality risks and the increasing one-year target vessel revascularization. At present, few articles reported on whether the incidence of CIN induced by isotonic and hypotonic contrast agent after PCI is different or not. Objectives To investigate the different effect of isotonic and hypotonic contrast agent in inducing CIN in patients with coronary artery disease after PCI. Methods We enrolled 355 patients with coronary artery disease who undertook PCI from January 2007 to December 2008 as subjects. Renal functions of all 355 patients were normal. Patients were randomly divided into isotonic group and hypotonic group. Concentrations of serum creatinine （SCr） were measured before, 48～72 hours and 7 days （if needed） after PCI. The glomerular filtration rate （eGFR） was calculated according to MDRD formula. The incidence of CIN was defined as the concentration of SCr ≥0.5 mg/dL（44.2 μmol/L）. Hemodialysis rates and mortality were recorded in the hospital. Results There was no significant difference in the basline eGFR （79.52±5.28 vs 81.03±6.09, P0.05）, dosages of contrast agent （125.68±15.88 mL vs 123.51±16.38 mL, P0.05）, eGFR of 48-72 hours after PCI （70.26±9.48 vs 69.06±9.59, P0.05） and incidences of CIN （5.56% vs 5.78%, P0.05） between the two groups. eGFR and concentrations of SCr 7 days after PCI showed no significant difference between the two groups （P0.05）. No patient was dead or needed hemodialysis in hospital. Conclusions The effect of isotonic and hypotonic contrast agent in inducing CIN in patients with coronary artery disease after PCI has no difference.
文摘Objective: To observe the time of ascites disappearance, time to ascites recurrence, improvement rate in quality of life, and the effective rate of ascites treatment in patients with advanced gastric and ovarian cancer with ascites following hypotonic hyperthermic intraperitoneal chemotherapy. Methods: Forty patients with advanced gastric and ovarian cancer with ascites, treated in our hospital from January 2021 to August 2024, were selected as research subjects. They were divided into a treatment group and a reference group using a random number table method. The treatment group received hypotonic hyperthermic intraperitoneal chemotherapy, while the reference group received conventional treatment. The treatment effects of the two groups were compared. Results: In the treatment group, the ascite disappearance time was (6.13 ± 1.32) days, and the recurrence time was (22.58 ± 8.21) months. The ascite disappearance time was significantly shorter than that of the reference group, and the ascite recurrence time was significantly longer. Both P-values were less than 0.05, indicating statistical significance. The effective rate of quality of life improvement was 95%, with only 1 patient showing a decrease in quality of life. The effective rate of ascites treatment was 95%, with only 1 patient showing an increase in ascites. Both the quality of life improvement rate and the effective rate of ascites treatment were significantly higher than those of the reference group, with P-values of 0.037 and 0.018, respectively, indicating statistical significance. Conclusion: For patients with advanced gastric and ovarian cancer with ascites, hypotonic hyperthermic intraperitoneal chemotherapy can accelerate ascites disappearance, prolong the time to recurrence, and significantly improve both the quality of life improvement rate and the effective rate of ascites treatment.
基金funds from the FEDER through the Operational Programme for Competitiveness Factors and Employment 2007-2013 (France)from the Cancérop?le Ile de France (France)
文摘Red blood cells(RBCs)can act as carriers for therapeutic agents and can substantially improve the safety,pharmacokinetics,and pharmacodynamics of many drugs.Maintaining RBCs integrity and lifespan is important for the efficacy of RBCs as drug carrier.We investigated the impact of drug encapsulation by hypotonic dialysis on RBCs physiology and integrity.Several parameters were compared between processed RBCs loaded with l-asparaginase(“eryaspase”),processed RBCs without drug and non-processed RBCs.Processed RBCs were less hydrated and displayed a reduction of intracellular content.We observed a change in the metabolomic but not in the proteomic profile of processed RBCs.Encapsulation process caused moderate morphological changes and was accompanied by an increase of RBCs-derived Extracellular Vesicles release.Despite a decrease in deformability,processed RBCs were not mechanically retained in a spleen-mimicking device and had increased surface-to-volume ratio and osmotic resistance.Processed RBCs half-life was not significantly affected in a mouse model and our previous phase 1 clinical study showed that encapsulation of asparaginase in RBCs prolonged its in vivo half-life compared to free forms.Our study demonstrated that encapsulation by hypotonic dialysis may affect certain characteristics of RBCs but does not significantly affect the in vivo longevity of RBCs or their drug carrier function.
文摘The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water(TBW) and total effective solute and is expressed in terms of the tonicity of the body fluids. Disturbances in tonicity are the main factor responsible for changes in cell volume, which can critically affect brain cell function and survival. Solutes distributed almost exclusively in the extracellular compartment(mainly sodium salts) and in the intracellular compartment(mainly potassium salts) contribute to tonicity, while solutes distributed in TBW have no effect on tonicity. The second body fluid balance concept relates to the regulation and measurement of abnormalities of sodium salt balance and extracellular volume. Estimation of extracellular volume is more complex and error prone than measurement of TBW. A key function of extracellular volume, which is defined as the effective arterial blood volume(EABV), is to ensure adequate perfusion of cells and organs. Other factors, including cardiac output, total and regional capacity of both arteries and veins, Starling forces in the capillaries, and gravity also affect the EABV. Collectively, these factors interact closely with extracellular volume and some of them undergo substantial changes in certain acute and chronic severe illnesses. Their changes result not only in extracellular volume expansion, but in the need for a larger extracellular volume compared with that of healthy individuals. Assessing extracellular volume in severe illness is challenging because the estimates of this volume by commonly used methods are prone to large errors in many illnesses. In addition, the optimal extracellular volume may vary from illness to illness, is only partially based on volume measurements by traditional methods, and has not been determined for each illness. Further research is needed to determine optimal extracellular volume levels in several illnesses. For these reasons, extracellular volume in severe illness merits a separate third concept of body fluid balance.
文摘Objective: It has been suggested that the use of hypotonic intravenous fluid (IVF) puts hospitalized children at a greater risk of developing hyponatremia in children with increased arginine vasopressin (AVP) production. To reduce its risk, the National Patient Safety Agency in UK issued alert 22 in 2007, of which recommendations were to use isotonic solutions for these children at risk of hyponatremia, instead of the previously most commonly used IVF (0.18% saline/ 4% dextrose) for maintenance fluid therapy. Recent observations, however, revealed that hypokalemia are also common in hospitalized patients who do not receive potassium in their IVF. This study was conducted to validate the potassium added IVF for the prevention of hospital-acquired hypokalemia in maintenance fluid therapy. Design: For maintenance fluid therapy, a commercially available IVF solution in Japan named as Solita-T2R (Na 84 mmol/L, K 20 mmol/L, Cl 66 mmol/L, glucose 3.2%) was infused for 41 sick children with a median age of 3.01 years. Its composition is close equivalent to 0.45% saline/5% dextrose (Na 77 mmol/L, K 0 mmol/L, Cl 77 mmol/L, dextrose 5%) except K content. The patients in states of AVP excess were excluded from the analysis. Results: Median serum potassium value did not drop significantly at a median interval of 48 hours (before IVF: 4.30 mmol/L, after IVF: 4.10 mmol/L, p > 0.05), whereas median serum sodium level significantly increased from 136.0 mmol/L to 139.0 mmol/L (p < 0.001). Conclusion: Potassium added (20 mmol/L) IVF solution reduces the risk of developing “hospital-acquired hypokalemia” in children who are not in states of AVP excess in maintenance fluid therapy. It is worthwhile to study prospectively in a larger number of sick children.
文摘Introduction: Intracellular calcium concentration ([Ca2+]i) is a critical parameter in cellular homeostasis, including articular chondrocytes. Perturbed [Ca2+]i of chondrocytes may be associated with joint disease. The objective of the study was to compare large animal models for investigating Ca2+ homeostasis in chondrocytes. Materials and Methods: The gross anatomy of the metacarpophalangeal joint (MCP) of cattle and sheep was compared, along with the effect of various manoeuvres used to study the mechanisms of Ca2+ homeostasis in chondrocytes from load-bearing areas. The gross anatomy was observed before and after dissection, and internal architecture was examined after sectioning. Cartilage thickness was measured with a digital micrometer. Chondrocyte yield was determined after isolation. Chondrocytes were incubated with Fura-2 and Ca2+i followed in different extracellular conditions. A hypotonic shock (HTS) was used to mimic removal of a load. Results: The results showed that ovids and bovids were skeletally immature and aspects of Ca2+ homeostasis were similar. Ovine chondrocytes had higher resting fluorescence, consistent with elevated resting Ca2+ levels. Results from ion substitution experiments were consistent with a role for Na+/Ca2+ exchange, and swelling-induced Ca2+ enters into the cytoplasm via the plasma membrane and intracellular stores. Conclusions: Ca2+ homeostasis in chondrocytes from both species behaved in a similar manner to HTS and ion substitutions. Differences in resting [Ca2+]i could be associated with species, stage of maturation, or Fura-2 itself and require further investigation. These findings contribute to our understanding of the physiology of articular cartilage in different species, and their potential use as models for studying joint disease in humans.
文摘NFAT5 plays a critical role in maintaining the renal functions. Its dis-regulation in the kidney leads to or is associated with certain renal diseases or disorders, most notably the urinary concentration defect. Hypertonicity, which the kidney medulla is normally exposed to,activates NFAT5 through phosphorylation of a signaling molecule or NFAT5 itself. Hypotonicity inhibits NFAT5 through a similar mechanism. More than a dozen of protein and lipid kinases have been identified to contribute to tonicity-dependent regulation of NFAT5. Hypertonicity activates NFAT5 by increasing its nuclear localization and transactivating activity in the early phase and protein abundance in the late phase. The known mechanism for inhibition of NFAT5 by hypotonicity is a decrease of nuclear NFAT5. The present article reviews the effect of each kinase on NFAT5 nuclear localization, transactivation and protein abundance, and the relationship among these kinases, if known. Cyclosporine A and tacrolimus suppress immune reactions by inhibiting the phosphatase calcineurin-dependent activation of NFAT1. It is hoped that this review would stimulate the interest to seek explanations from the NFAT5 regulatory pathways for certain clinical presentations and to explore novel therapeutic approaches based on the pathways. On the basic science front, this review raises two interesting questions. The first one is how these kinases can specifcally signal to NFAT5 in the context of hypertonicity or hypotonicity, because they also regulate other cellular activities and even opposite activities in some cases. The second one is why these many kinases, some of which might have redundant functions, are needed to regulate NFAT5 activity. This review reiterates the concept of signaling through cooperation. Cells need these kinases working in a coordinated way to provide the signaling specificity that is lacking in the individual one. Redundancy in regulation of NFAT5 is a critical strategy for cells to maintain robustness against hypertonic or hypotonic stress.
基金supported by grants from the National Natural Science Foundation of China(32330044 and 32170951 to Y.S.S.,82201615 to X.Y.T.,and 82271891 to J.C.)the Guangdong High Level Innovation Research Institute(2021B0909050004 to Y.S.S.)+2 种基金the National Key R&D Program of China(2019YFA0801603 to Y.S.S.)the Natural Science Foundation of Jiangsu Province(BK20240251 to C.Y.)the Fundamental Research Funds for the Central Universities(02141438053 to Y.S.S)。
文摘Elevated glucose metabolism triggers two primary processes that lead toβ-cell depolarization and insulin secretion:the closure of ATPsensitive K+channels via ATP-dependent mechanisms and the activation of mechanosensitive channels(MSCs)due to cell swelling.However,the identity of these MSCs remains unclear.In this study,we found that TMEM63B is a stretch-activated cation channel(SAC)crucial for regulating insulin secretion in response to elevated glucose levels.TMEM63B is abundantly expressed inβ-cells,and its deletion impairs insulin secretion triggered by high glucose.High glucose levels typically increase Ca2+influx and firing frequency inβ-cells,a response largely eliminated when TMEM63B is deleted.Mechanistically,glucose metabolism induces cell swelling and activates TMEM63B,which,in turn,leads toβ-cell depolarization and insulin secretion.In conclusion,our findings demonstrate that TMEM63B is an SAC essential for regulating insulin secretion in response to elevated glucose levels.
基金The publication was prepared with the support of the Omsk State Medical University and RUDN University Program 5-100
文摘Objective:To evaluate the effectiveness of the use of a modified Zhukovsky double(vaginal and uterine)balloon to improve the results of treatment in women with obstetric hemorrhage.Methods:We conducted an observational controlled study including 701 puerperas,which were divided into two groups:The main group consisted of 508 women,who underwent a combined management,that is,traditional(transfusion of fresh frozen plasma,erythrocyte mass,uterotonics,hemostatic agents),surgical hemostasis in cases of caesarean section,and insertion of a double Zhukovsky balloon;while the comparison group included 193 patients,who were managed traditionally.The main group and the comparison group were divided into subgroups according to the main etiology of obstetric hemorrhage:ⅠA andⅠB-postpartum;ⅡA andⅡB-placenta accreta;ⅢA andⅢB-postpartum hysterectomy.Results:The most frequent causes of massive obstetric hemorrhage were atony of the uterus(39.2%),placenta previa(29.1%),and placental abruption(11.5%).Of the 508 balloon insertions,345(70.7%)were inserted for hemorrhage during cesarean section and 148(29.3%)for obstetric hemorrhage after spontaneous delivery.Among the obstetric hemorrhage at caesarean section,lower segment bleeding prevailed(78.1%),caused mainly by placenta previa,placenta accreta,placental abruption,polyhydramnios,and uterine scar defects.Combined management,including surgical hemostasis and insertion of vaginal and uterine balloon of Zhukovsky,reduced blood loss by 1.5 times and the number of hysterectomies by 6.72 times compared to controls.Conclusion:The use of a modified Zhukovsky double balloon in the management of obstetric hemorrhage may reduce the number of hysterectomies and the amount of blood loss.
