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Diabetic kidney disease （DKD） is a common microvascular complication of diabetics mellitus （DM） and the leading cause of end-stage renal disease （ESRD）. Renal interstitial fibrosis （RIF） is the primary pathological basis for DKD progression to ESRD， which significantly increases the mortality rate of DKD patients and burdens patients and society， and it is thus a clinical problem that needs to be solved urgently. The pathogenesis of RIF is complex and mainly associated with excessive deposition of extracellular matrix （ECM）， epithelial-mesenchymal transition （EMT）， oxidative stress， inflammation， and autophagy. Multiple signaling pathways such as transforming growth factor-β1/Smad （TGF-β1/Smad）， nuclear transcription factor-κB （NF-κB）， p38 mitogen-activated protein kinase （p38 MAPK）， secretory glycoprotein/β-catenin （Wnt/β-catenin）， mammalian target of rapamycin （mTOR）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， neurogenic site-gap homologous protein （Notch）， and nuclear factor E2-associated factor 2 （Nrf2） mediate the development of RIF， which are currently novel targets for DKD therapy. Due to the complexity of its pathogenesis， the current Western medical treatment mainly focuses on essential treatment to improve metabolism， which has poor efficacy and is difficult to prevent the progression of DKD， so it is significant to find new treatment methods clinically. In recent years， many studies have proved that traditional Chinese medicine can alleviate oxidative stress， inhibit inflammatory response， and regulate cellular autophagy by modulating relevant signaling pathways， so as to treat RIF in DKD， which has the advantages of multi-pathway， multi-targeting， multi-linking， and significant therapeutic efficacy. However， there is still a lack of relevant summary. By reviewing the latest research reports in China and abroad， this article examines the roles of the signaling pathways mentioned above in the occurrence and development of RIF in DKD and the recent research progress in the intervention of RIF in DKD by traditional Chinese medicine via these pathways， aiming to provide new ideas and references for further scientific research and clinical practice.
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Metastasis is the leading cause of cancer-related death. Despite extensive treatment, the prognosis for patients with metastatic cancer remains poor. In addition to conventional surgical resection, radiotherapy, immunotherapy, chemotherapy, and targeted therapy, various nanobiomaterials have attracted attention for their enhanced antitumor performance and low off-target effects. However, nanomedicines exhibit certain limitations in clinical applications, such as rapid clearance from the body, low biological stability, and poor targeting ability. Biomimetic methods utilize the natural biomembrane to mimic or hybridize nanoparticles and circumvent some of these limitations. Considering the involvement of immune cells in the tumor microenvironment of the metastatic cascade, biomimetic methods using immune cell membranes have been proposed with unique tumor-homing ability and high biocompatibility. In this review, we explore the impact of immune cells on various processes of tumor metastasis. Furthermore, we summarize the synthesis and applications of immune cell membrane-based nanocarriers increasing therapeutic efficacy against cancer metastases via immune evasion, prolonged circulation, enhanced tumor accumulation, and immunosuppression of the tumor microenvironment. Moreover, we describe the prospects and existing challenges in clinical translation.
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Lung cancer is the malignant tumor with the highest morbidity and mortality in China. Non-small cell lung cancer (NSCLC) is the main pathological subtype of lung cancer. On April 13, 2023, the National Comprehensive Cancer Network (NCCN) released the third edition of the 2023 NCCN Oncology Clinical Practice Guidelines: Non-small Cell Lung Cancer, which reflects the latest advances in international lung cancer research. This article will interpret the main updated contents of the new edition of the guidelines, and compare it with the third edition of the NCCN guidelines in 2022, so as to provide references about the diagnosis and treatment of NSCLC for clinical medical personnel in China. .
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Humans , Carcinoma, Non-Small-Cell Lung , China , Lung Neoplasms , ThoraxABSTRACT
Objective To investigate the relationship between the treatment of EGFR-TKI icotinib and the prognosis of advanced lung adenocarcinoma patients with EGFR mutation. Methods Patients with advanced lung adenocarcinoma who had EGFR19 and 21 gene mutations and were treated with EGFR-TKI icotinib were enrolled. The relationships of clinical features, EGFR gene mutation subtypes, and different sites with patients'prognosis were analyzed. Results A total of 101 patients with advanced lung adenocarcinoma were included in this study, including 58 cases (57.4%) of EGFR gene exon 19 deletion mutation (EGFR Del19) and 43 cases (42.6%) of EGFR gene exon 21 point mutation (EGFR L858R). The objective response rate was 63.4%. The mPFS and mOS were 13 months and 27 months, respectively. In addition, the mPFS and mOS of EGFR Del19 and EGFR19 mutation 746-750 were higher than those of EGFR L858R and other EGFR mutations, respectively. Meanwhile, multivariate analysis showed that the number of metastatic sites and pleural metastasis were independent influencing factors of patients'OS (P=0.027; P=0.041). The mOS of patients with the number of metastatic sites ≤3 and without pleural metastasis were 29 and 27 months, respectively. Conclusion There is no significant difference found in overall survival of advanced lung adenocarcinoma patients treated with icotinib among different EGFR mutation subtypes and sites. Herein, the overall survival time is longer in patients with less than three metastatic sites and without pleural metastasis.
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Objective:To study the regulatory effects of transforming growth factor beta-activated kinase 1 (TAK1) on microglia pyroptosis in hypoxic-ischemic brain damage (HIBD).Methods:Primary microglia cells were isolated from fetal mice and randomly assigned into 4 groups: the control group, 5z-7-oxozeaneol (5z-7) group, oxygen-glucose deprivation (OGD) group and OGD+5z-7 group. OGD models of microglia cells were established for the OGD groups and 5z-7 groups received a small molecule TAK1 inhibitor 5z-7. Expression of phosphorylated TAK1(P-TAK1), pyroptosis related proteins including NOD-like receptor pyrin domain containing 3 (NLRP-3), apoptosis-associated speck-like protein containing a CARD (ASC) oligomers, N terminal of Gasdermin D (GSDMD-N) and interleukin 1β (IL-1β) were examined using Western blot at 0 h, 6 h and 24 h after intervention. Lactate dehydrogenase (LDH) test and transmission electron microscope were used for pyroptosis evaluation.Results:(1) Compared with the control group, expressions of all proteins including P-TAK1, NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH level showed no significant differences in the OGD group at 0 h ( P>0.05). P-TAK1 levels in OGD group at 6 h and 24 h were lower than the control group and the levels of NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH were significantly higher ( P<0.05). Microglia pyroptosis (characterized by disruption of cell membrane, extravasation of cytoplasm and chromatin margin aggregation) was observed under electron microscope. (2) 5z-7 group and OGD+5z-7 group had lower P-TAK1 levels and higher NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH levels than the control group and OGD group at 6 h and 24 h. Conclusions:The down-regulation of TAK1 phosphorylation level may promote microglia pyroptosis in HIBD. This regulatory effects is related to the up-regulation of NLRP-3 expression and the oligomerization of ASC.
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Acute mononuclear leukemia is a type of disease with a high incidence in acute myeloid leukemia. With the continuous deepening of traditional Chinese medicine research, some progress has been made in the research on its clinical efficacy and mechanism of action. This article reviews the research progress in the treatment of acute mononuclear leukemia with traditional Chinese medicine in recent years.
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Small cell lung cancer (SCLC) is the most malignant lung cancer with the highest mortality. At present, the first-line standard treatment is still based on Etoposide and Platinum chemotherapy. However, for SCLC that progresses after first-line therapy, the treatment options are still very limited. Since the molecular mechanism of first-line drug resistance of SCLC is still unclear, and the precision medicine strategy after first-line drug resistance is still in the pre-clinical stage. The proportion of secondary biopsy and genetic testing is very low after the progress of first-line treatment of SCLC. In this study, we report a case of a middle-aged woman who was first diagnosed with SCLC. Adenocarcinoma with sensitive gene mutations and repeated changes of small cell carcinoma were detected by multiple biopsies during the course of the disease, suggesting that the patient may be a special subtype of SCLC - mixed SCLC (M-SCLC). In this case, the patient has been treated with radiotherapy and chemotherapy, immunotherapy and targeted therapy successively, and the survival time has reached 2 years and 8 months. Through the case report and literature review retrospectively, this study aimed to explore the part patients may start to present hybrid histopathologic types or tissue type change after treatment of SCLC. Biopsy pathologic histology and genetic testing is necessary after disease progression to look for potential therapeutic targets, so as to give precise treatment based on molecular markers detection results and provide the patient with the benefit of survival for as long as possible. .
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Female , Humans , Middle Aged , Adenocarcinoma of Lung , Etoposide , Lung Neoplasms/genetics , Retrospective Studies , Small Cell Lung Carcinoma/geneticsABSTRACT
Placental injury is the main cause of morbidity and mortality during perinatal period. Intraoperative bleeding and hysterectomy rate have risen significantly with the increase of placenta accreta. Prenatal ultrasound is superior to MRI in blood flow display. The progresses of ultrasound in observation on normal maternal fetal circulation and blood flow changes of placenta accreta were reviewed in this article.
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OBJECTIVE@#To observe the therapeutic effect of tetramethylpyrazine on immune-mediated bone marrow failure (BMF) induced by different doses of X-ray exposure in C57 mice.@*METHODS@#C57BL6 mice were randomized into 4 groups, including a blank control group and 3 X-ray exposure groups with X-ray exposure at low (5.0 Gy), moderate (5.75 Gy), and high (6.5 Gy) doses. After total body irradiation with 0.98 Gy/min X-ray. The mice as recipient received injections of 4×10 lymphocytes from DBA/2 mice via the tail vein within 4 h. The survival rate of the recipient mice, peripheral blood cell counts, bone marrow nucleated cell count, and bone marrow pathology were examined at 14 days after the exposure. In the subsequent experiment, C57 mice were exposed to 5.0 Gy X-ray and treated with intraperitoneal injection of tetramethylpyrazine at the low (5 mg/mL), moderate (10 mg/mL), or high (20 mg/mL) doses (12 mice in each group) for 14 consecutive days, and the changes in BMF were observed.@*RESULTS@#X-ray exposure, especially at the high dose, resulted in significantly lowered survival rate in the mouse models of BMF at 14 days. As the X-ray dose increased, the mice showed significantly reduced peripheral blood counts of red blood cells, white blood cells, platelets and lowered bone marrow nucleated cell counts with obvious bone marrow congestion and reduction of nucleated cells ( < 0.05 or 0.001). In the mice exposed to 5.0 Gy X-ray, tetramethylpyrazine at the high dose most obviously increased bone marrow nucleated cells ( < 0.01) and red blood cells ( < 0.001), and even at the low dose, tetramethylpyrazine significantly increased the counts of white blood cells ( < 0.05) and platelets ( < 0.01) following the exposure. Tetramethylpyrazine dose-dependently alleviated bone marrow hyperemia, increased bone marrow nucleated cell counts, and lowered Fas protein expression in the bone marrow.@*CONCLUSIONS@#X-ray irradiation at 5.0 Gy is suitable for establish mouse models of immune-mediated BMF. Tetramethylpyrazine promotes bone marrow repair by regulating Fas cell apoptosis signals, which further expands the traditional Chinese medicine theory of "removing blood stasis to create new."
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Animals , Mice , Bone Marrow , Mice, Inbred C57BL , Mice, Inbred DBA , Pyrazines , Whole-Body IrradiationABSTRACT
Acute ischemic stroke (AIS), as the third leading cause of death worldwide, is characterized by its high incidence, mortality rate, high incurred disability rate, and frequent reoccurrence. The neuroprotective effects of Ginkgo biloba extract (GBE) against several cerebral diseases have been reported in previous studies, but the underlying mechanisms of action are still unclear. Using a novel in vitro rat cortical capillary endothelial cell-astrocyte-neuron network model, we investigated the neuroprotective effects of GBE and one of its important constituents, Ginkgolide B (GB), against oxygen-glucose deprivation/reoxygenation and glucose (OGD/R) injury. In this model, rat cortical capillary endothelial cells, astrocytes, and neurons were cocultured so that they could be synchronously observed in the same system. Pretreatment with GBE or GB increased the neuron cell viability, ameliorated cell injury, and inhibited the cell apoptotic rate through Bax and Bcl-2 expression regulation after OGD/R injury. Furthermore, GBE or GB pretreatment enhanced the transendothelial electrical resistance of capillary endothelial monolayers, reduced the endothelial permeability coefficients for sodium fluorescein (Na-F), and increased the expression levels of tight junction proteins, namely, ZO-1 and occludin, in endothelial cells. Results demonstrated the preventive effects of GBE on neuronal cell death and enhancement of the function of brain capillary endothelial monolayers after OGD/R injury in vitro; thus, GBE could be used as an effective neuroprotective agent for AIS/reperfusion, with GB as one of its significant constituents.
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Animals , Rats , Apoptosis , Brain Ischemia , Drug Therapy , Cell Survival , Cells, Cultured , Disease Models, Animal , Endothelial Cells , Ginkgolides , Pharmacology , Glucose , Lactones , Pharmacology , Neurons , Neuroprotective Agents , Pharmacology , Oxygen , Plant Extracts , Pharmacology , Stroke , Drug TherapyABSTRACT
[Objective] To investigate the theory of"Treat Pre-disease"about intermenstrual bleeding from TCM constitution. [Methods] Intermenstrual bleeding is a disease of the gynecology, and it is more likely to relapse. Constitution theory of TCM holds that people's physique has the character of separable, adjustable and physique relating to disease. [Results] The interphase bleeding in patients with often clinical performance for yin deficiency constitution,qi deficiency constitution, damp heat constitution, blood-stasis constitution. [Conclusion] We can use the "Treat Pre-disease" thought to correct the physical deviation of the patients with intermenstrual bleeding, preventing the disease and preventing its recurrence after cure.
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Placental implantation (PI) is a serious complication of obstetrics and gynecology,which threatens the safety of the mothers and children.Prenatal ultrasound has become the preferred imaging method due to its universality,ecnomic ly and high sensitivity,but the diagnostic efficacy of the indicators is still controversial.The diagnostic value and advantages of various indicators of prenatal ultrasound in the diagnosis of PI were reviewed in this article.
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Placental implantation (PI) is a serious complication of obstetrics and gynecology,which threatens the safety of the mothers and children.Prenatal ultrasound has become the preferred imaging method due to its universality,ecnomic ly and high sensitivity,but the diagnostic efficacy of the indicators is still controversial.The diagnostic value and advantages of various indicators of prenatal ultrasound in the diagnosis of PI were reviewed in this article.
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Objective To explore the correlation between the fluctuation of blood glucose levels and brain damage in neonates with hypoglycemia. Methods The clinical data of 58 cases of neonatal hypoglycemia diagnosed from September 2013 to August 2016 were analyzed retrospectively. According to the results of neonatal cranial MRI and/or amplitude integrated electroencephalogram (aEEG), the neonates were divided into brain injury group and non-brain injury group. The fluctuation index of blood glucose was compared between two groups, and the correlation between the fluctuation of blood glucose level and brain injury was analyzed. Results In these 58 cases, 13 cases were in brain injury group (8 males and 5 females) and 45 cases were in non-brain injury group (27 males and 18 females). The lowest blood glucose (LBG) value in brain injury group was lower than that in non-brain injury group, while the duration of hypoglycemia, maximum blood glucose fluctuations (LAGE), standard deviation of blood glucose (SDBG), and average blood glucose fluctuations (MAGE) were higher than those in non-brain injury group, and they were all significantly different (P all<0.001). Conclusions Whether the hypoglycemia in newborn could lead to the brain injury or not depends not only on the minimum hypoglycaemia level and duration of hypoglycemia, but also on the indicators of glucose variation, such as LAGE, SDBG and MAGE.
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Objective:To analyze the effects of protein intake of varied dietaries on the pregnancy of pregnant women.Methods:The pregnant women who had their medical records in our hospital were included in this study.Their dietary were collected based on the respective review of their food during 24 hours when they visited the Nutrition Clinics between 24 weeks and 28 weeks.The subjects were divided into six groups according to the dietary calories and protein intake:group A (normal calorie and normal protein),group B (normal calorie and low protein),group C (normal calorie and high protein),group D (high calorie and normal protein),group E (high calorie and high protein) and group F (low calorie and low protein).The gestational diabetes mellitus incidence rates,levels of fasting blood glucose (FBG),blood glucose (BG),hemoglobin Alc (HbAlc),and blood lipids,and bone mineral density were compared among six groups.Results:The gestational diabetes mellitus incidence rate,levels of postprandial blood glucose at 1 hour and 2 hour in groups of B,C,D,and E were significantly higher than those in group A (P ＜ 0.05).The levels of triglyceride,total cholesterol,and low density lipoprotein cholesterol were remarkably higher in groups of B,D,and E than those in group A (P ＜ 0.05).The bone mineral density was significantly lower in group A than that in groups of C,E,and F (P ＜ 0.05).Conclusion:The diet with normal calorie and normal protein is the scientific dietary structure.The pattern with high calorie and high protein intake is not recommended for pregnant women.
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Objective To explore and build a real, objective, comprehensive clinical nursing individual performance indicators architecture model,and check the rationality and validity for prize distribution by clinical application. Methods The methods included that discuss new ideas of nursing performance management by multi- disciplinary experts,developed clinical personal nursing staff performance evaluation program,worded out indicators and methods for the clinical assessment of individual nurses and nurse managers respectively,then applied research in the pilot departments and hospital step by step. Results A personal performance evaluation framework model was constructed, which include clinical nurses and nursing managers. Experimental results show that the nursing staff in this regard performance program have a high degree of recognition, 98.82% (1 741/1 762) nursing staff understanding of the purpose and significance, 97.15%(1 712/1 762) nurses think the performance model structure is reasonable. After the implementation of the performance program, the outstanding rate of personal performance appraisal of nurses was 93% (1 639/1 762). Conclusions The application of scientific performance appraisal programs can play a positive role in helping improve the quality of clinical care, and promote the stable development of the care team.
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Objective To investigate the effect of meridian-unblocking and mind-regulating acupuncture pretreatment on neurobehavioral functions and cerebral water content and explore its mechanism for modulating miRNA664 and MMP9 expressions in cerebral ischemia/reperfusion rats.Methods One hundred and thirty Wistar rats were randomized into group A (electroacupuncture pretreatment) of 30 rats, group B (moxibustion pretreatment) of 30 rats, group C (aspirin pretreatment) of 30 rats, group D (model) of 30 rats and group E (blank control) of 10 rats. Group A received electroacupuncture; group B, suspended moxibustion with moxa sticks; group C, an oral gavage of aspirin 10 mg/kg. A model of cerebral ischemia/reperfusion was made in every group after seven days. Rat neurobehavioral functions were observed and cerebral water content and relative miRNA664 and MMP9 expressions in the cortical region were determined at 24 hours after reperfusion.Results There was a statistically significant difference in the neurobehavioral score between group A, B, C or D and group E (P<0.01), between group A or B and group C (P<0.01) and between groups A and B (P<0.01). There were statistically significant differences in cerebral water content and relative miRNA664 and MMP9 expressions between group A, B, C or D and group E (P<0.01,P<0.05), between group A, B or C and group D (P<0.01), between group A or B and group C (P<0.01,P<0.05) and between groups A and B (P<0.01,P<0.05).Conclusions Meridian-unblocking and mind-regulating acupuncture pretreatment can effectively decrease the neurobehavioral score and cerebral water content and reduce relative MMP9 expression through modulating miRNA664 expression in cerebral ischemia/reperfusion rats. One of the mechanisms of Du meridian-unblocking and mind-regulating acupuncture pretreatment for protecting the brain may be reducing relative MMP9 expression, inducing tolerance to cerebral ischemia and relieving cerebral edema by the modulation of miRNA664 expression.
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Objective To observe the effect of modified Bazhen Decoction ( MBD) on bone marrow fibroblast growth factor-1 ( FGF-1) in chronic aplastic anemia ( CAA) patients. Methods Sixty cases of CAA were randomly divided into treatment group and control group, 30 cases in each group. Both groups were given conventional western medicine such as oral use of Stanozolol and Ciclosporin, and additionally, the treatment group received oral use of MBD. Six months constituted one treatment course for both groups. After treatment, the clinical efficiency in western medicine field and on Chinese medical syndromes was evaluated in both groups. The changes of peripheral hemogram, adverse reaction, and FGF-1 in the bone marrow of both groups were also monitored. Results ( 1) Clinical efficacy in western medicine field was 80.0% in the treatment group, and was 66.7%in the control group (P<0.05). (2) The total effective rate on Chinese medical syndromes was 100.0% in the treatment group, and was 83.3%in the control group (P<0.05). (3) After treatment, the scores of symptoms were decreased in both groups (P<0.05 or P<0.01 compared with those before treatment), and the decrease in the treatment group was superior to that in the control group (P<0.05). (4) Peripheral white blood cell (WBC) count, hemoglobin (HGB) content and platelet (PLT) count as well as bone marrow FGF-1 were increased in both groups after treatment (P<0.01 compared with those before treatment), and the increase of WBC, HGB, PLT and FGF-1 in the treatment group was superior to that in the control group (P<0.05). (5) In the aspect of the adverse reaction, the treatment group had 2 cases of hepatic fucntion injury, and one case of acne and hairiness; the control group had 2 cases of gum hypertrophy, 5 cases of hepatic function injury, and 4 cases of acne and hairiness. The control group had higher incidence of adverse reaction ( P<0.05). Conclusion MBD exerts certain therapeutic effect for CAA, and one of the possible mechanisms is related with the regulation of FGF-1 level.
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<p><b>OBJECTIVE</b>To probe into the function of stem cell antigen-1 (Sca-1) in cell proliferation and differentiation.</p><p><b>METHODS</b>Sca-(1+) and Sca-(1-) muscle derived cells were separated from C57BU6 mice by fluorescence-activated cell sorting and then cultured in vitro. After 5 days cells proliferative curve were drawn according CCK-8 experimental results. Western blot also were done to detect Sca(-1), MyoD and Myogenin expression in cultured Sca(-1+) and Sca-(1-) muscle derived cells.</p><p><b>RESULTS</b>The difference of the proliferative curve of Sca-(1+) and Sca-(1-) muscle derived cells cultured 3 days in vitro was not apparent, but Sca-(1-) muscle derived cells had a accelerated division rate in the follow days compared to the Sca-(1+) muscle derived cells. Sca-1 expression in both cells was not obvious. MyoD and Myogenin expression were stronger in Sca-(1+) than Sca-(1-) muscle derived cells.</p><p><b>CONCLUSION</b>Sca-1 expression in muscle derived cells takes a period of time that related to the beginning and ending of the cell cycle.</p>
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Animals , Mice , Antigens, Ly , Cell Differentiation , Cell Proliferation , Cells, Cultured , Flow Cytometry , Membrane Proteins , Muscle, Skeletal , Myogenin , Stem CellsABSTRACT
Cell adhesion molecules(CAMs) play important roles in specifying cell-cell interactions during development,regeneration,and modification of synaptic activity.The close homolog of L1(CHL1) ,a recently identified member of the immunoglobulin superfamily of cell adhesion molecules,is localizably expressed in the nervous system.CHL1 interacts with like molecules(homophilic interaction) and non-like molecules(heterophilic interaction) on neighboring cells or the extracellular matrix to regulate axon outgrowth and fasciculation,neuronal migration and survival,synaptic plasticity and regeneration after trauma.