The crosstalk between ferroptosis and mitochondrial dynamic regulatory networks.

Ferroptosis is an iron-driven cell death modality characterized by iron accumulation and excessive lipid peroxidation. Ferroptosis is closely related to mitochondrial function, as indicated by studies showing that mitochondrial dysfunction and damage promote oxidative stress, which in turn induces ferroptosis. Mitochondria play crucial roles in cellular homeostasis, and abnormalities in their morphology and function are closely associated with the development of many diseases. Mitochondria are highly dynamic organelles, and their stability is maintained through a series of regulatory pathways. Mitochondrial homeostasis is dynamically regulated, mainly via key processes such as mitochondrial fission, mitochondrial fusion and mitophagy; however, mitochondrial processes are prone to dysregulation. Mitochondrial fission and fusion and mitophagy are intimately related to ferroptosis. Therefore, investigations into the dynamic regulation of mitochondrial processes during ferroptosis are important to provide a better understanding of the development of disease. In this paper, we systematically summarized changes in ferroptosis, mitochondrial fission and fusion and mitophagy to promote an in-depth understanding of the mechanism underlying ferroptosis and provide a corresponding reference for the treatment of related diseases.

Effect of 25G+pars plana vitrectomy combined with preoperative intravitreal injection of Conbercept on proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical effect of 25G+pars plana vitrectomy(PPV)combined with preoperative intravitreal injection of conbercept in the treatment of patients with proliferative diabetic retinopathy(PDR), and analyze the influence on visual acuity, central foveal thickness(CMT)and serum vascular endothelial growth factor(VEGF)level.METHODS: A retrospective study was conducted from October 2019 to January 2022. A total of 80 patients(87 eyes)with PDR were divided into the two groups according to the treatment method, with 40 patients(45 eyes)treated with 25G+PPV in the control group, and 40 patients(42 eyes)treated with 25G+PPV combined with preoperative intravitreal injection of conbercept in the observation group. The two groups were compared in terms of the best corrected visual acuity(BCVA), intraocular pressure, CMT and serum VEGF level before treatment and at 2wk, 1 and 3mo after treatment. The patients were followed up for 3mo, with postoperative complications and recurrence recorded.RESULTS: The incidence of intraoperative bleeding in the observation group was significantly lower than that in the control group(P<0.05). After treatment, the BCVA of the two groups was improved(P<0.05), CMT and serum VEGF level were decreased(P<0.05), but there was no significant change in intraocular pressure(P>0.05). The BCVA and CMT of observation group were lower than those of control group at 1 and 3mo after treatment(P<0.05). Serum VEGF level in the observation group was lower than that in the control group at 3mo after treatment(P<0.05). The incidence of complications in observation group(5%)within 3mo after treatment was significantly lower than that in control group(18%; P<0.05). There was no statistically significant difference in recurrence rate of PDR between the two groups(P>0.05).CONCLUSION: With few complications, 25G+PPV combined with preoperative intravitreal injection of conbercept is effective in the treatment of patients with PDR, which can better promote postoperative vision recovery, improve macular edema, and reduce serum VEGF level.

Anterior abdominal abscess - a rare manifestation of severe acute pancreatitis: A case report.

BACKGROUND: Severe acute pancreatitis (SAP) is a common critical disease of the digestive system. In addition to the clinical manifestations and biochemical changes of acute pancreatitis, SAP is also accompanied by organ failure lasting more than 48 h. SAP is characterized by focal or extensive pancreatic necrosis, hemorrhage and obvious inflammation around the pancreas. The peripancreatic fat space, fascia, mesentery and adjacent organs are often involved. The common local complications include acute peripancreatic fluid collection, acute necrotic collection, pancreatic pseudocyst, walled off necrosis and infected pancreatic necrosis. After reviewing the literature, we found that in very few cases, SAP patients have complications with anterior abdominal wall abscesses. CASE SUMMARY: We report a 66-year-old Asian male with severe acute pancreatitis who presented with intermittent abdominal pain and an increasing abdominal mass. The abscess spread from the retroperitoneum to the anterior abdominal wall and the right groin. In the described case, drainage tubes were placed in the retroperitoneal and anterior abdominal wall by percutaneous puncture. After a series of symptomatic supportive therapies, the patient was discharged from the hospital with a retroperitoneal drainage tube after the toleration of oral feeding and the improvement of nutritional status. CONCLUSION: We believe that patients with SAP complicated with anterior abdominal abscess can be treated conservatively to avoid unnecessary exploration or operation.

Dynamics of carbon stocks of different pools in Huzhong National Nature Reserve, Northeast China under the disturbance of various severity fires.

In this study, the FireBGCv2 model was used to simulate the dynamics of forest carbon pools of Huzhong Nature Reserve within the next 100 years under various forest fire severity scena-rios. The aim of this study was to explore the responses of different forest carbon pools to fire disturbance, and to provide scientific basis for forest fuel management. The results showed that forest fire significantly reduced forest carbon storage, with the greatest reduction under the scenario of high-severity forest fire. Fire disturbance affected carbon storage in different pools, and relocated carbon among those pools. Forest fire disturbance reduced carbon storage of living trees and duff, increased that of coarse woody debris in the early and middle stages of simulation, and decreased that in late stage. The carbon storage of shrub and herb strata increased significantly in the late simulation period. The higher the fire severity, the lower the carbon storage of living tree and shrub-herb carbon pools, with snag and coarse woody debris showing the opposite trend. The impact of forest fire disturbance on the total carbon pool distribution was as follows: forest fire increased the proportion of shrub and herb strata, snag, coarse woody debris and soil carbon pool, and reduced the proportion of living tree and duff. The higher severity forest fire was, the lower the proportion of carbon pool of shrub-herb, and the higher the proportion of carbon pool of coarse wood debris. The severity of forest fire had less impact on the proportion of other carbon pools. In addition, our results demonstrated periodic change of litter carbon that reached a high value within 20 years and then dropped to a low value within 10 years. Our results could provide sound basis for determining the forest fuel treatment interval. We suggested performing prescribed burning every 20 years in the Great Xing'an Mountains area to protect forest resources.

Extracellular vesicles and pancreatitis: mechanisms, status and perspectives.

Comprehensive reviews and large population-based cohort studies have played an important role in the diagnosis and treatment of pancreatitis and its sequelae. The incidence and mortality of pancreatitis have been reduced significantly due to substantial advancements in the pathophysiological mechanisms and clinically effective treatments. The study of extracellular vesicles (EVs) has the potential to identify cell-to-cell communication in diseases such as pancreatitis. Exosomes are a subset of EVs with an average diameter of 50~150 nm. Their diverse and unique constituents include nucleic acids, proteins, and lipids, which can be transferred to trigger phenotypic changes of recipient cells. In recent years, many reports have indicated the role of EVs in pancreatitis, including acute pancreatitis, chronic pancreatitis and autoimmune pancreatitis, suggesting their potential influence on the development and progression of pancreatitis. Plasma exosomes of acute pancreatitis can effectively reach the alveolar cavity and activate alveolar macrophages to cause acute lung injury. Furthermore, upregulated exosomal miRNAs can be used as biomarkers for acute pancreatitis. Here, we summarized the current understanding of EVs in pancreatitis with an emphasis on their biological roles and their potential use as diagnostic biomarkers and therapeutic agents for this disease.

Role of inflammatory regulators in neovascularization of diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#Diabetic retinopathy(DR)is one of the common diseases that can lead to blindness, and its complicated pathogenesis has not been elucidated completely at present. Many studies have emerged that chronic inflammation plays a prominent role in the pathogenesis of DR. That many “hot spots”of inflammatory molecules, such as IL-6, IL-1β, TNF-α, and MCP-1,are involved in the part of essential mechanism of disease through complex and intertwined inflammatory pathways in the recently research. Above inflammatory factors and angiogenic factors will promote each other, especially when pathological neovascularization occur, which is greatly increasing in severity of the disease. The article made a general debate about the effect of inflammation in DR, and the relationship between inflammation and neovascularization.

[Effects of Xiangdan Injection on pharmacokinetics and pharmacodynamics of warfarin in rats in vivo].

This study is to explore the effect of Xiangdan Injection on anticoagulation of warfarin in rats. Rats were randomly divided into different groups and then administered, subsequently the blood samples were collected at a set series of time points to measure PT(prothrombin time) and APTT(activated partial thromboplastin time) values, and INR(international normalized ratio) value was calculated. The plasma concentrations of warfarin enantiomers were determined by UPLC-MS/MS technology, and pharmacokinetic parameters were calculated by DAS 2.0 software. Statistical analysis was performed to compare differences between the groups. Single-dose study of warfarin showed that Xiangdan Injection alone had no effects on PT, APTT and INR, but when co-administrated with warfarin, PT and INR values were increased(P<0.01), while APTT was unaffected; after co-administration of the two drugs, C_(max), AUC_(0-t), and AUC_(0-∞) of S-warfarin increased(P<0.01), and t_(1/2) prolonged(P<0.01), while the pharmacokinetic parameters of R-warfarin were not changed significantly. Steady-state study of warfarin showed that after co-administration of the two drugs, the PT and INR values increased(P<0.05), and the plasma concentration of S-warfarin increased(P<0.01), while the plasma concentration of R-warfarin was not changed significantly. The results suggest that Xiangdan Injection itself has no effect on coagulation index, but can enhance the anticoagulant effect of warfarin by slowing metabolism of S-warfarin.

Characterization of Endothelial Cells Associated with Cerebral Arteriovenous Malformation.

INTRODUCTION: Cerebral arteriovenous malformation (cAVM) is a disease characterized by the angiogenesis and remodeling of veins. However, whether vascular endothelial cells (ECs) exhibit morphological and functional changes during cAVM remains unclear. This study aimed to investigate the role of ECs in the pathogenesis of cAVM. METHODS: Rat model of cAVM was established by anastomosing the common carotid artery with the external jugular vein. The digital subtraction angiography (DSA), HE, Masson and immunohistochemical staining were performed to evaluate the model. ECs were isolated from AVM rat model or control rats, and characterized by MTT, cell scratch, and tube formation assays. The secretion of vascular endothelial growth factor (VEGF) was detected by ELISA. RESULTS: AVM rat model showed typical pathological characteristics of cAVM. In addition, the proliferation, migration and tube formation abilities of ECs of arterialized vein (AV-ECs) were significantly better than those of ECs of normal vein (NV-ECs). Moreover, the levels of secreted VEGF were significantly higher in AV-ECs than in NV-ECs. CONCLUSION: AV-ECs isolated from AVM rat model showed increased proliferation, migration and angiogenesis and may be potential target for the treatment of cAVM.

The effects of tectochrysin on prostate cancer cells apoptosis and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of tectochrysin on prostate cancer cell line 22Rv.1 and reveal its molecular mechanism.@*METHODS@#Tectochrysin at the concentrations of 0～20 μg/ml was applied to 22Rv.1 cells and normal prostate cell RWPE-1. The proliferation activity of the cells was detected by MTS assay. Flow cytometry and hoechst 33342 staining were used to analyze the effects of drugs on cell apoptosis, death, cell cycle and nuclear type changes. LDH release test was used to analyze the cytotoxicity of the drug to 22Rv.1 cells. QPCR and Western blot were used to analyze the effects of the drug on the expressions of genes in 22Rv.1 cells. Finally, the tumor inhibited effect of the drug on the bearing tumor BALB/c mice were confirmed though anti-tumor experiment.@*RESULTS@#Tectochrysin could significantly inhibit the proliferation activity of 22Rv.1 cells and induced their apoptosis, and promoted the expressions of genes dr4, dr5, trail, p53, caspase-3, caspase-8, caspase-9, bid, bax and foxo3, inhibited the expressions of anti-apoptotic genes akt, pi3k and bcl-2.@*CONCLUSION@#Tectochrysin can induce prostate cancer cells apoptosis through affecting TRAIL and PI3K/AKT signaling pathways, and has anti-prostate cancer effect.

Effects of 2-12alkyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione(DMDD)on diffuse large B lymphoma and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects and molecular mechanisms of 2-12alkyl-6-methoxycyclohexa-2,5-diene-1,4-dione(DMDD) on diffuse large B lymphoma (DLBCL).@*METHODS@#In animal experiments, 4-week-aged BALB/C mice were divided into 5 groups, 20 mice in each group. Mice were inguinal injected with DLBCL cell line OCI-LY19 cells 0.1 ml at the concention of 1 × 10 /ml. Two days later, mice were treated with DMDD at the doses of 0, 1, 5, 25 and 125 mg/kg by intragastric administration respectively, once /2 days. Ten mice of each group were killed on the 18th day of administration, and the tumor tissues were weighed. The survival time of the remaining mice were recorded. In cell experiments, OCI-LY19 cells were added to 96-well culture plates, 100 μl 1×10 cells/ml per well, then 100 μl DMDD was added to the well and the final concentrations were 0, 1, 5, 25 and 125 μmol/L respectively. The cells were treated with DMDD for 0, 24, 48 and 72 h, three wells in each group. The cell proliferation activity was detected by MTS assay. According to the results of cell proliferation experiments, OCI-LY19 cells were treated with DMDD at the concentrations of 0 μmol/L, 5 μmol/L and 25 μmol/L for 24 h. The apoptosis rate was analyzed by flow cytometry, the nuclear type was observed by hoechst staining, the mitochondrial membrane potential was observed by JC-1 staining, cytotoxicity of drugs was evaluated by LDH release experiment, gene expression and transcription were analyzed by qPCR and Western blot.@*RESULTS@#Compared with 0 mg/kg drug group, DMDD at the dose of 1～125 mg/kg could inhibit the growth of tumor tissue in mice and prolong their survival time (P＜0.01). Cell experiments showed: in DMDD group, the proliferation activity of OCI-LY19 cells was decreased significantly and the level of apoptosis was increased significantly (P＜0.01), nuclear fragmentation, agglutination, apoptotic bodies occurred and mitochondrial membrane potential was decreased, the LDH release rate was increased significantly (P＜0.01), the expressions of caspase-3 and bax genes and the phosphorylation level of Ikappa B alpha in cells were up-regulated significantly, the protein expression levels of bcl-2, bcl-xL, jak2 and stat3 were inhibited significantly (P＜0.01).@*CONCLUSION@#DMDD can inhibit the expressions of JAK2, STAT3 and p-Ikappa B alpha in JAK2/STAT3 and NF-kappa B signal pathways, down-regulate BCL-2/BAX and activate Caspase-3, finally, activate the endogenous pathway of mitochondrial apoptosis in OCI-LY19 cells and promote the apoptosis of DLBCL cells, inhibit proliferation of OCI-LY19 cells. It has inhibitive effects on DLBCL.

Anti-hepatoma effects of Smac analogue Birinapant and its related molecular mechanism / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of Birinapant on hepatocellular carcinoma cells and its related molecular mechanisms.@*METHODS@#Human hepatocellular carcinoma cells QGY-7701 were treated with 0, 1, 5, 25 and 125 nmol/L Birinapant for 24, 48 and 72 hours respectively, each experiment 3 wells.The proliferation activity of cells, the apoptosis levels, the cells nuclear type, the mitochondrial membrane potential, the transcription and expression levels of genes and the cytotoxicity of Birinapant were analyzed.At the same time, 4-week-old male BALB/C mice were randomly divided into 5 groups, with 20 mice in each group.The mice were inguinal injected with QGY-7701 cells, and then subcutaneous injected with Birinapant (concentrations ranging from 0, 1, 5, 25, 125 μg/kg) in each group after two days, once every other day.On 18 day since first Birinapant injection, 10 mice were killed in each group to weigh tumor tissue and survival time was recorded from the remaining 10 mice.The effects of Birinapant on the growth of the tumor and the survival time of tumor-bearing mice were observed.@*RESULTS@#Compared with the negative control (NC) group, the proliferation activity of QGY-7701 was inhibited significantly after Birinapant treatment and the apoptosis levels were increased significantly (<0.01).The cell mitochondrial membrane potential was decreased and the karyotype was changed (<0.01).At the same time, the transcription and expression levels of genes cellular inhibitor of apoptosis protein 1(cIAP-1), cellular inhibitor of apoptosis protein 2(cIAP-2), ras, raf, mek and erk were significantly decreased (<0.01), while the expression levels of caspase-3 and caspase-9 genes were up-regulated (<0.01).Compared with the model group (MG), the growth of the tumor was inhibited significantly and the survival time of the tumor-bearing mice was prolonged after Birinapant treatment (<0.01).@*CONCLUSIONS@#Birinapant can inhibit the expression of cIAP-1, cIAP-2 and the proteins of Ras-Raf-MEK-ERK signal pathways, so as to activate the mitochondria mediated endogenous apoptosis pathway.Birinapant shows a certain inhibitory effect on liver cancer.

Protective effects of human bone marrow mesenchymal stem cells on hematopoietic organs of irradiated mice / 中国实验血液学杂志

The objective of this study was to explore the protective effects of human bone marrow mesenchymal stem cells (MSC) on hematopoietic organs of irradiated mice. Human bone marrow MSC were isolated, ex vivo expanded, and identified by cell biological tests. Female BALB/c mice were irradiated with (60)Co γ-ray at a single dose of 6 Gy, and received different doses of human MSC and MSC lysates or saline via tail veins. The survival of mice was record daily, and the femurs and spleens were harvested on day 9 and 16 for pathologic examination. The histological changes were observed and the cellularity was scored. The results showed that the estimated survival time of MSC- and MSC lysate-treated mice was comparable to that of controls. The hematopoiesis in the bone marrow of mice that received high-dose (5×10(6)) of MSC or MSC lysates was partially restored on day 9 and the capacity of hemopoietic tissue and cellularity scorings were significantly elevated as compared with that of controls (P < 0.05). Proliferative nudes were also obviously observed in the spleens of mice that received high-dose of MSC or MSC lysates on d 9 after irradiation. The histological structures of the spleen and bone marrow of the mice that received high-doses (5×10(6)) of MSC or MSC lysates were restored to normal, the cell proliferation displayed extraordinarily active. Further, the cellularity scores of the bone marrow were not significantly different between the high-dose MSC and MSC lysate-treated mice. It is concluded that the bone marrow MSC can promote the hematopoietic recovery of the irradiated mice, which probably is associated with the bioactive materials inherently existed in bone marrow cells.

One-year continuous observation of change in peripheral T cell subsets in workers exposed to low levels of benzene / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the T cell subsets and blood cells in the peripheral blood of workers exposed to low levels of benzene for one year, and to investigate the relationship between T cell function impairment and benzene-induced hematopoietic injury after benzene exposure.</p><p><b>METHODS</b>Eighty-eight workers (58 males and 30 females, aged 18 ∼ 22 years) who just began to work in the workshop of a paint factory with exposure to benzene in Guangzhou, China were assigned to experimental group, and 88 workers (58 males and 30 females, aged 18 ∼ 25 years) who worked in the workshop without exposure to benzene were selected as controls. The blood samples of the workers were examined once every 4 months to measure the percentages of peripheral T cell subsets and peripheral blood cell counts in the one-year study. The benzene concentrations at operation points were also measured.</p><p><b>RESULTS</b>The peripheral blood cell counts in the benzene-exposed workers had no significant changes in the first and second examinations; the white blood cell (WBC) counts in the experimental group in the third and fourth examinations were significantly lower than that in the control group [(6.4 ± 3.0)×10(9)/L and (6.3 ± 2.7)×10(9)/L vs (7.3 ± 3.0)×10(9)/L, P < 0.05], and the platelet (PLT) count in the experimental group in the fourth examination was also significantly lower than that in the control group[(179 ± 74)×10(9)/L vs (189 ± 70)×10(9)/L, P < 0.05]. Compared with those in the control group (CD4+: 54.29 ± 12.78%, CD8+: 37.25 ± 12.30%), the percentage of CD3+ T cells in the experimental group increased in the third examination; the percentage of CD4+ T cells in the experimental group decreased continuously in the second, third, and fourth examinations (50.77 ± 11.05%, 45.40 ± 9.41%, and 41.27 ± 10.62%), while the percentage of CD8+ T cells in the experimental group kept increasing (46.07 ± 10.18%, 50.36 ± 10.62%, and 56.40 ± 9.41%) (P < 0.05).</p><p><b>CONCLUSION</b>The change in T cell subsets precedes that in the blood system in the workers exposed to low levels of benzene.</p>

Effects of human umbilical cord mesenchymal stem cells in the treatment of paraquat-induced lung injury / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the clinical effect and safety of human umbilical cord mesenchymal stem cells (HUCMSCs) in the treatment of lung injury caused by acute paraquat poisoning.</p><p><b>METHODS</b>Thirteen patients with lung injury caused by acute paraquat poisoning, who were admitted to Guangzhou No. 12 People's Hospital from December 2008 to December 2012, were divided into HUCMSC group (n = 5) and control group (n = 8). All patients received conventional treatment, while the HUCMSC group was treated with HUCMSCs as an addition. Sequential Organ Failure Assessment (SOFA) system, which was created by the Infection Section of European Society of Intensive Care Medicine, and Acute Physiology and Chronic Health Evaluation II were used to acquire the SOFA scores of patients. The lung injury was evaluated with lung injury score (LIS). The two groups were compared with respect to maximum SOFA scores at 1, 3, 5, 7, 14, and 15 days after paraquat poisoning.</p><p><b>RESULTS</b>The HUCMSC group showed significantly lower maximum SOFA scores than the control group at 15d after poisoning (1.80 ± 2.05 vs 13.50 ± 7.59, P < 0.05). The LISs of the HUCMSC group after treatment (0.45 ± 0.27) were significantly lower than those of the HUCMSC group before treatment (1.15 ± 0.34) and those of the control group after treatment (2.94 ± 1.20) (P < 0.01). In the HUCMSC group, all patients survived, and they complained no discomfort and showed normal liver, kidney, and lung functions in reexamination; one patient showed incompletely absorbed shadow in the posterior segment of the left lower lobe of the lung during lung CT scan, and no abnormal findings were seen in other patients. In the control group, one patient survived, and others died. No adverse reactions, such as chill and fever, were presented in the HUCMSC group.</p><p><b>CONCLUSION</b>HUCMSCs show promise for clinical application in the treatment of lung injury caused by acute paraquat poisoning.</p>

Therapy of aplastic anemia with autologous peripheral mononuclear cells treated by IL-2 and GM-CSF in culture: a long-term follow-up report on 49 patients / 中国实验血液学杂志

This study was purposed to evaluate the long-term outcome and the safety of autologous peripheral blood mononuclear cells (PBMNC) treated by interleukin 2 (IL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF) in the therapy of patients with aplastic anemia (AA). The therapy of 49 patients admitted BG in hospital from April 2001 to December 2007 were analyzed retrospectively. PBMNC were isolated and cultured for 48 hours in presence of IL-2 and GM-CSF. Cells were collected, and 6 × 10(6) - 1 × 10(8) PBMNC were intravenously injected weekly for 4 - 22 months. Hematopoietic recovery was evaluated by examinations of peripheral blood, bone marrow aspirates and bone marrow biopsy. Flow cytometry was used to assess the peripheral T cell subsets before and after treatment. Polymerase chain reaction was performed to observe the clonal diversity of T cell receptor variable β-chain (TCR-Vβ) recombination. The results showed that 37 cases were cured and none of them relapsed during the follow-up, 5 cases were in partial remission, 3 cases got improvement, and 4 cases showed no response. The total efficiency reached up to 91.8%. The ratios of CD4(+)/CD8(+) subsets were abnormal in 39 patients prior to the treatment, and 31 cases restored to the normal range after cell transfusions. Analysis on the clonal diversity of TCR-Vβ recombination in 11 patients showed the transition from monoclonal or biclonal spectratype to polyclonal one. No long-term side effects were documented. It is concluded that the treatment with PBMNC treated by IL-2 and GM-CSF is generally safe and effective. The underlying mechanisms may be in relation to the restoration of cell immunity.

Hepatocyte growth factor combined with autologous bone marrow mesenchymal stem cell transplantation for treatment of silicosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the potential role of hepatocyte growth factor (HGF) combined with bone marrow mesenchymal stem cells (BMSC) autograft for the treatment of silicosis.</p><p><b>METHODS</b>Bone marrow (100 ml) was aspirated from a severe silicosis patient. BMSCs isolated, purified and cultured in vitro. When BMSC came to 70% confluence at passage 3, the culture medium was added liposomes (lipo2000) and plasmid-HGF (p-HGF) and cultured for 2 d. HGF-MSCSs (5 × 10(7) cells) were resuspended in 50 ml 0.9% sodium chloride (NS) and infused Intravenous drip at 3 consecutive times (once a week). Clinical follow-up were performed before and after treatment: (1) pulmonary high-kV X-ray, chest CT examination; (2) pulmonary function test; (3) determination of serum ceruloplasmin.</p><p><b>RESULTS</b>The symptoms such as coughing, chest tightness disappeared at 12 months after treatment. Pulmonary function tests showed significant changes after treatment: forced vital capacity (FVC) increased from 64.6% to 81.0%, forced expiratory volume in one second (FEV(1.0)) increased from 68.7% to 90.1%, 1 second rate (FEV(1.0)/FVC%) reduced from 111.6% to 107.1%, the maximum mid-expiratory flow (FEF(25%∼75%) decreased from 100.2% to 94.6%, forced expiratory vital capacity 75% of the moment bit of gas flow (MEF(75%)) increased from 99.2% to 113.5%, forced expiratory vital capacity 50% of the moment bit of gas flow (MEF(50%)) increased from 125.3% to 130.2%, forced expiratory vital capacity 25% of the moment bit of gas flow (MEF(25%)) reduced from 86.9% to 71.7%; serum ceruloplasmin levels decreased from 690 mg/L to 180.6 mg/L; lung high-kV X-ray at 1st review showed that diffuse lung nodules had been absorbed and getting smaller than before treatment; chest CT showed that the distribution and number of small nodules at double lung fields decreased than before treatment.</p><p><b>CONCLUSION</b>HGF combined with BMSC transplantation may have some potential role for the treatment of silicosis patients.</p>

The comparative study of quartz dust and bleomycin-induced pulmonary fibrosis in rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To compare the pulmonary alveolitis and the early fibrosis of pulmonary fibrosis induced by quartz dust and bleomycin in rats, and investigate their mechanism.</p><p><b>METHODS</b>The female rats were divided into three groups: control group exposed to normal saline by the trachea; SiO2 group exposed to SiO2 by the trachea; BLM group exposed to BLM A5 by the trachea. Each half of the animals were sacrificed on the 7th and 14th day after exposure. The lungs of rats were collected to observe pulmonary alveolitis by HE staining and to observe fibrosis by saturated picric acid sirius red staining. The expression of tumor necrosis factor-alpha (TNF-alpha) and CD68 in pulmonary tissues were analyzed quantitatively by immunohistochemistry and image analysis system.</p><p><b>RESULTS</b>(1) The alveolitis and pulmonary fibrosis of rats in both SiO2 group and BLM group were became more serious gradually over time, HE staining under light microscope showed that BLM group on the 7th day had the most obvious alveolitis (2.814 +/- 0.832), the saturated picric acid sirius red staining under polarized light showed that BLM group on the 14th day had the worst pulmonary fibrosis (1284.57 +/- 554.72), which were significantly higher than those (103.69 +/- 18.29 and 111.78 +/- 37.45) in control group and SiO2 group on the 7th day (P < 0.05). (2) The results of immunohistochemistry examination indicated that the expression (17.100 +/- 1.831) of TNF-alpha in the BLM group on the 7th day was significantly higher than those (0.451 +/- 0.441, 7.909 +/- 1.275 and 13.506 +/- 1.454) in control group, SiO2 group on 7th day and BLM group on 14th day (P < 0.05). The expression (22.778 +/- 2.512) of TNF-alpha in the SiO2 group on the 14th day was significantly higher than those in control group, SiO2 group on 7th day and BLM group on 14th day (P < 0.05). The expression (134.941 +/- 35.951) of CD68 in the SiO2 group on the 14th day was significantly higher than those in control group, SiO2 group on 7th day and BLM group on 14th day (P < 0.05).</p><p><b>CONCLUSION</b>The early alveolitis of BLM-induced lung injury model was more serious than that of SiO2-induced lung injury model, and the fibrosis process of BLM-induced lung injury model was earlier than that of SiO2-induced lung injury model. TNF-alpha plays an important role in the course of both models, but macrophages is involved in SiO2-induced pulmonary in a more continuous way than in BLM-induced pulmonary fibrosis.</p>

The experimental study of suppressing silicosis fibrosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To compare the difference of effects on SiO(2)-induced alveolitis and early fibrosis between bone marrow-derived mesenchymal-like stem cells (BM-MSCs) and BM-MSCs transfected by pcDNA3.1-HGF and to explore the mechanism of this effects.</p><p><b>METHODS</b>The Primary BM-MSCs from Wistar male young rats were cultured and labeled by 4, 6-diamidino-2-phenylindole (DAPI). Fifty Wistar rats were randomly divided into 3 groups:model group (10 rats),which was administered with SiO(2) by the trache, the next day,injected PBS via the tail vein; BM-MSCs group (20 rats),which was administered with SiO(2) by the trache, the next day,injected with 1 ml suspension of BM-MSCs via the tail vein; pcDNA3.1-HGF plus BM-MSC group (20 rats),which was administered with SiO(2) by the trache, the next day,injected with 1 ml suspension of BM-MSCs transfected by pcDNA3.1-HGF via the tail vein. On the 14th and 28th days after treatment, half of the animals were sacrificed, respectively, and the lungs were harvested for frozen section to observe the cell marked by DAPI. HE staining under a fluorescent microscope, and to observe the pulmonary alveolitis and fibrosis by HE and Masson staining under a light microscope. Western blot assay was used to detect the expression of HGF in rat lungs. The expression levels of tumor necrosis factor-α (TNF-α) in pulmonary tissues were analyzed quantitatively by ELISA. The contents of HYP in pulmonary tissues were analyzed quantitatively by sample hydrolysis method.</p><p><b>RESULTS</b>On the 14th and 28th days after treatment, the scores of pulmonary alveolitis and early fibrosis in pcDNA3.1-HGF plus BM-MSCs group were 2.36 ± 0.17, 2.8 ± 0.14 and 0.1 ± 0.11, 1.16 ± 0.13, which were significantly lower than those (1.68 ± 0.17, 1.58 ± 0.31 and 0.54 ± 0.15, 1.36 ± 0.13) in BM-MSCs group, also which were significantly lower those (2.36 ± 0.17, 2.80 ± 0.14 and 0.64 ± 0.09, 1.84 ± 0.17) in model group (P < 0.05); On the 14th and 28th days after treatment, the TNF-α contents of pulmonary tissues in pcDNA3.1-HGF plus BM-MSCs group were 280.4 ± 23.11 and 249.78 ± 22.33 pg/mg, which were significantly lower than those (341.58 ± 35.34, 442.29 ± 36.76 pg/mg and 319.51 ± 17.84, 348.53 ± 33.95 pg/mg) in BM-MSCs and model groups (P < 0.05); On the 14th and 28th days after treatment, the HYP contents of pulmonary tissues in pcDNA3.1-HGF plus BM-MSCs group were 0.46 ± 0.04 and 0.65 ± 0.05 µg/mg, which were significantly lower than those (0.63 ± 0.04, 1.04 ± 0.07 µg/mg and 0.72 ± 0.60, 1.39 ± 0.60 µg/mg) in BM-MSCs and model groups (P < 0.05).</p><p><b>CONCLUSION</b>The effects of BM-MSCs transfected by pcDNA3.1-HGF on suppressing pulmonary alveolitis and early fibrosis induced by SiO2 were better than those of BM-MSCs. The mechanism may be associated with the reduced pulmonary inflammation.</p>

Investigating the treatment of silicosis with autologous bone marrow-derived mesenchymal stem cells / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the safety and curative effects of autologous bone marrow-derived mesenchymal stem cells (BMSCs) in the treatment of silicosis.</p><p><b>METHODS</b>The protocol was approved by the Ethics Committee of the hospital, and ten patients with silicosis who had given written consent were enrolled in this study. BMSCs isolated from 100 ml of bone marrow for each case were purified and cultured. In each case the 3rd generation of qualified BMSCs (5 × 10(7)) were intravenously administered weekly for 3 weeks. Three cases among 10 patients were treated with BMSCs modified by hepatocyte growth factor (HGF) gene. The clinical symptoms, chest films, chest CT, pulmonary functions, T cells, serum IgG and ceruloplasmin (CP) were observed in 6 or 9 months after treatment.</p><p><b>RESULTS</b>No obvious sub-effect was observed in cases treated with BMSCs, the clinical symptoms (such as cough, sputum and chest tightness) basically disappeared in 9 months after treatment. Pulmonary function tests showed that FVC increased from 71.2% ± 17.0% to 84.0% ± 10.9% (P < 0.01) and FEV1.0 increased from 67.5% ± 17.7% to 80.6% ± 14.9% (P < 0.01). The levels of serum CP and IgG significantly decreased (P < 0.01). Further, the chest films and CT in cases treated with autologous BMSCs modified by HGF gene were improved to different extent.</p><p><b>CONCLUSION</b>Treatment with autologous BMSCs modified by HGF gene exhibit a beneficial effect on silicosis.</p>

Abnormal increase in CD8(low) T lymphocyte in patients with occupational chronic lead poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To analyze the changes in CD8(low) T lymphocyte subsets in patients with occupational chronic lead poisoning.</p><p><b>METHODS</b>Flow cytometric analysis was used to count the numbers of CD8+ cells. 23 patients with occupational chronic lead poisoning and 20 controls were examined.</p><p><b>RESULTS</b>Compared with control group (8.21% ± 3.02%), the CD8(low) T lymphocyte (12.98% ± 5.62%) were significantly increased in patients with occupational chronic lead poisoning.</p><p><b>CONCLUSION</b>Although the ratio of CD+ T lymphocyte is normal, the CD8 level is significantly decreased. The increase of CD8(low) T lymphocyte may be an important phenomenon of immuno-injury induced by lead. CD8(low) T lymphocyte could be an new direction for research of lead immuno-toxicity.</p>