الملخص
ObjectiveTo explore the molecular mechanism of Qidi Tangshen prescription （QDTS） in regulating podocyte pyroptosis in diabetes nephropathy （DN）. MethodThrough in vivo experiment， db/db mice were divided into the model group， QDTS group （3.34 g·kg-1）， valsartan capsule group （10.29 mg·kg-1）， with db/m mice serving as the normal control. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and kidney pathological changes were observed. Additionally， the expression levels of pyroptosis-related indicators， including NOD-like receptor protein 3 （NLRP3）， Gasdermin D protein （GSDMD）， and interleukin-1β （IL-1β） protein， were examined. Through in vitro experiment， mouse podocytes were divided into the normal glucose group （5.5 mmol·L-1 glucose）， high glucose group （35 mmol·L-1 glucose）， DMSO group （35 mmol·L-1 glucose+200 mg·L-1 DMSO）， and QDTS group （35 mmol·L-1 glucose+200 mg·L-1 QDTS freeze-dried powder）. After 48 hours of intervention， the expression levels of NLRP3， GSDMD， and IL-1β proteins were measured in podocytes. A drug-ingredient-target-disease interaction network for QDTS in the treatment of DN was constructed by network pharmacology methods. The key signaling pathways regulating podocyte pyroptosis were analyzed， and validation was conducted through in vivo and in vitro experiments. ResultCompared with normal group， glomerular hyperplasia and glomerular basement membrane thickening were observed in model group， and some segments were accompanied by obvious podocellular process fusion. The protein expressions of NLRP3， GSDMD and IL-1β in mouse kidney were increased， the protein expressions of mitogen-activated protein kinase 14 （MAPK14）， V-Rel reticuloendotheliosis virus oncogene homology A （RELA） and Caspase-8 in mouse kidney were increased （P<0.05）. Compared with model group， kidney pathological injury of mice in QDTS group was significantly reduced， and the expressions of NLRP3， GSDMD and IL-1β in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. The protein expressions of MAPK14， RELA and Caspase-8 in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. Network pharmacology results showed that there were 16 targets for QDTS to regulate DN cell pyrodeath， among which MAPK14， RELA and Caspase-8 were the key targets. Compared with normal glucose group， the protein expressions of NLRP3， GSDMD and IL-1β in high glucose group were increased （P<0.05）， and the protein expressions of MAPK14， RELA and Caspase-8 in mouse podocytes were increased （P<0.05）. Compared with high glucose group， the expressions of NLRP3， GSDMD and IL-1β in podocytes of mice in QDTS group were decreased （P<0.05）， and the expressions of MAPK14， RELA and Caspase-8 in podocytes of mice in QDTS group were decreased （P<0.05）. ConclusionQDTS reduces damage to DN podocytes， which is associated with its regulation of the MAPK14/RELA/Caspase-8 signaling pathway and inhibition of podocyte pyroptosis.
الملخص
ObjectiveTo explore the mechanism of Qidi Tangshen prescription （QDTS） in alleviating podocyte injury and reducing urinary protein in diabetic nephropathy （DN）. MethodUsing network pharmacology methods， we collected the chemical components and targets of QDTS， as well as the targets related to DN. Subsequently， we constructed a "drug-ingredient-target-disease" network for QDTS in the treatment of DN to systematically elucidate the mechanism. The db/db mice were assigned into the model， QDTS （3.34 g·kg-1）， and losartan capsules （10.29 mg·kg-1） groups， and db/m mice served as the normal group. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and the urinary albumin excretion rate （UAER） and renal pathological changes were measured and observed. The expression levels of protein kinase B1 （Akt1）， hypoxia-inducible factor-1 alpha （HIF-1α）， phosphorylated B-cell lymphoma-extra-large （p-Bcl-xl）， as well as autophagy-related indicators microtubule-associated protein 1 light chain 3 （LC3）， ubiquitin-binding protein p62 （p62）， and autophagy-related gene 6 homolog （Beclin1）， were determined. Furthermore， mouse podocytes were divided into the normal glucose （5.5 mmol·L-1）， high glucose （35 mmol·L-1）， DMSO （35 mmol·L-1 glucose+200 mg·L-1 DMSO）， and QDTS （35 mmol·L-1 glucose+200 mg·L-1 QDTS freeze-dried powder） groups. After 48 h of intervention， the protein levels of Akt1， HIF-1α， p-Bcl-xl， LC3， p62， and Beclin1 in podocytes were measured. ResultQDTS had 34 active components acting on 143 targets in the treatment of DN， and 55 targets were related to autophagy， in which Akt1， HIF-1α， and Bcl-xl were the key targets. Compared with the normal group， mice in the model group exhibited significantly increased UAER， glomerular hypertrophy， deposition of blue collagen fibers， thickening of the glomerular basement membrane， and noticeable fusion of podocyte foot processes in some segments. Furthermore， the modeling up-regulated the protein levels of p-Akt1， HIF-1α， and p62 and down-regulating the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. Compared with the model group， QDTS and losartan decreased UAER （P<0.05） and alleviated the pathological damage in the renal tissue. Moreover， QDTS and losartan down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. In comparison to the normal glucose group， the high glucose group displayed up-regulated protein levels of p-Akt1， HIF-1α， and p62 and down-regulated protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. Compared with the high glucose group， QDTS down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. ConclusionQDTS alleviates podocyte damage and reduced urinary protein in DN by regulating the Akt1/HIF-1α/Bcl-xl signaling pathway， thereby enhancing podocyte autophagy.
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Objective To investigate the effects of different high-fat diet feeding time durations on blood glucose (BG), insulin resistance index(HOMA-IR), and urinary albumin excretion rate(UAER)in rats with high fat diet-induced type 2 diabetic nephropathy(DN). Methods Unilateral renal artery ligation, high-fat diet(throughout the ex-periment period),and low dose streptozotocin(STZ)intraperitoneal injection were used to establish a type 2 DN rat mod-el. After the operation,rats in the DN1 and DN2 groups received an intraperitoneal injection of STZ 30 mg/kg after 4 and 8 weeks of high-fat diet feeding,respectively. UAERs of the DN1 and DN2 groups were compared at 4 weeks after the STZ injection and the end of study(EOS). BG,body weight,HOMA-IR,kidney index,and pathological changes of the kidney were observed. Results UAER was increased in both groups at 4 weeks after the STZ injection,but significantly higher in the group DN2 than in the DN1 group(P<0.01). At the end of study(the 12th week),the renal tissues showed patho-logical changes,including glomerular capillary loop hypertrophy,increased mesangial matrix,and decreased capsule space in both groups. Compared with the DN1 group,the body weight was significantly higher(P<0.01),kidney index was sig-nificantly lower(P<0.01),while BG,serum insulin level,HOMA-IR,and UAER were no significantly changed in the DM2 group(P>0.05,respectively). Conclusions The results show that extending the feeding time of high-fat diet can aggravate the kidney damages in diabetic rats,but it can also delay the start of any planned intervention. Therefore,the ex-perimental protocol should be carefully designed based on the study objective.
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<p><b>OBJECTIVE</b>To assess the influence of assisted reproductive technology(ART) on the incidence of fetal chromosomal abnormalities by analyzing spontaneous abortions during the first trimester following natural conception(NC) or assisted reproductive technology(ART).</p><p><b>METHODS</b>Three hundred and fourteen chorionic villus samples of women with first trimester spontaneous abortion were collected. Cell culture and G-banding karyotyping analysis were carried out, which included 125 cases by in vitro fertilization(IVF), 87 cases by intracytoplasmic sperm injection(ICSI) and 102 cases by natural conception(NC).</p><p><b>RESULTS</b>Chromosomal aberrations were found in 167(53.2%) of the 314 cases. No significant difference was found in the spectrum of karyotypic abnormalities between NC and ART groups. The incidence of chromosomal abnormalities has increased along with the maternal age. Compared with the fresh embryo-transfer(ET) group, frozen-thawed embryo transfer(FET) group showed a slightly lower incidence of chromosomal abnormalities, albeit with no statistical significance(47.3% vs. 53.8%, P>0.05).</p><p><b>CONCLUSION</b>Fetal chromosomal abnormalities are the main cause for spontaneous abortion during the first trimester regardless the ways of conception. Their incidence is associated with maternal age. FET is relatively safe as well as fresh ET. ART is a relatively safe treatment which does not increase the rate of fetal chromosomal abnormalities.</p>
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Through analyzing the problems of time,selection mode,research plan,and tracking review in the ethical review of scientific research projects,this paper put forward the corresponding countermeasures:standardized application procedures,diverse selection mode,standardized research plan,and strict tracking review.It aimed to improve the quality of ethical review of scientific research projects and improve the ethical review system.
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Since the Beijing health and family planning commission promulgated the new medical technology management system,we have accepted and reviewed 14 key medical technologies in Beijing,such as resection of the skull base tumor (intracranial tumor outside communication),resection of intracranial important functional areas and large vascular malformation,renal vascular reconstruction technique,the technique of artificial joint replacement,coronary interventional diagnosis and treatment technology,etc.Through the existing laws and regulations requirements from medical new technology,the ethical review way,submit materials requirements and ethical review focus is analyzed,and combining with the experiences of our hospital in the medical technical review,aims to explore suitable for medical technology ethical review specification.
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This article was based on the investigation of ethical research in traditional Chinese medicine (TCM) clini-cal trials among 240 ischemic stroke patients and 105 experts specialized in this field. Analysis was given on the re-search results. This article was intended to regulate the ethical review of ischemic stroke, and to protect the rights and interests of the subjects better.
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Objective This clinical research will compare the constitution of patients with positive and negative family history in order to study on the relation between TCM constitution and the familial hereditary in type 2 diabetes patients.Methods The data of family history,general conditions,Chinese medical constitutional types of 231 type 2 DM patients in Dongzhimen Hospital were collected and analyzed.Results Among patients with family history,the number of patients' mothers with diabetes was significantly more than that of fathers'(x2=22.319,P＜0.05).There was a positive correlation between phlegm-dampness constitution r=0.215,blood stagnant constitution r=0.268 and female patients' family history(P＜0.01).And there was a positive correlation between the familial hereditary of DM and the familial hereditary of hypertension r=0.328,hyperlipidemia r=0.223,obesity r=0.151 and coronary artery diseases r=0.215.Conclusion Among type 2 DM,female had stronger familial hereditary.It indicated that diabetic mothers had a stronger influence on following generations than diabetic fathers,especially those female patients of phlegm-dampness constitution or blood stagnant constitution.There was inner correlation between the familial hereditary of DM and the familial hereditary of hypertension,hyperlipidemia,obesity and coronary artery disease.
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With the high incidence of diabetic nephropathy, the clinical trials of traditional Chinese medicine (TCM) in diabetic nephropathy area play an important role in the development of this subject. Therefore, follow-ing the principles of medical ethics, issues of fully understanding professional requirements of ethics review for clinical research of diabetic nephropathy and the protection of patients' rights are questions which should be solved. This article was based on the investigations on ethical needs of experts and patients in diabetic nephropathy area of TCM clinical trials . Discussions and considerations were made on results . A the more per-fect and regulated medical informed consent formwork for diabetic nephropathy of TCM clinical trials was made based on these consultations .
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A case of ulerythema ophryogenes (UO) is reported.A 12-year-old boy presented with erythema and follicular papules on the eyebrows and cheeks for 7 years.The lesions started as follicular papules surrounded by erythema,then spread symmetrically to the cheeks and forehead followed by the loss of eyebrows.There was no complaint of pruritus.Physical examination showed pinhead- to grain-sized,smooth,slightly indurated follicular hyperkeratotic papules surrounded by erythematous halo on the eyebrows,forehead and cheeks.Both eyebrows were nearly completely lost.Histological analysis of lesions from eyebrows revealed dilated follicular infundibulum with orthokeratotic plugs,sparse perivascular and perifollicular lymphohistiocytic infiltrate,widened and sclerotic collagen fibers in the dermis.According to the clinical manifestations and histopathological findings,the patient was diagnosed with ulerythema ophryogenes,and given oral vitamin A 2.5 million unit once a day,vitamin E 100 mg once a day,topical vitamine E cream twice a day,0.025％tretinoin ointment once at night.Two weeks later,the lesions improved.
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To investigate the effects of Astragalus membranaceus and Potentilla discolor mixture (APM) on insulin resistance (IR) and mRNA expressions of IR-related genes, including phosphatidylinositol 3-kinase (PI3-K), phosphoenolpyruvate carboxykinase (PEPCK) and peroxisome proliferator-activated receptor γ coactivator 1 (PGC1) in KKAy mice with early type 2 diabetes and to explore the gene regulation mechanisms of AMP.
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Objective To Analyze the distribution characteristics of Hyperthyroidism's syndrome and the relationship between symptoms and thyroid hormones. Methods The TCM syndromes of a total of 78 patients with hyperthyroidism were differentiated. The relationship between syndrome and general condition of patients (gender and age, etc.) were analyzed;correlation between symptoms and thyroid hormones were also studied. Results Of all 78 patients, patients with yin deficiency and hyperactive yang accounted for 43.6%; patients with internal disturbance of phlegm-fire accounted for 30.8 %; and patients with hypteracitivity of heart-fire and liver-fire accounted for 25.6%. The severity of all the symptoms showed positive correlation with hyroid hormones (the value of r is positive, P＜0.05); and no linear relationship with TSH (P＞0.05).Conclusion The syndrome of yin deficiency and hyperactive yangI was the most common syndrome type. Thyroid hormones had direct proportion with the severity of syndrome.
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Objective To evaluate the effect of endoluminal treatment for Budd Chiari syndrome (BCS) .Methods In 36 patients with BCS were treated by inferior vena cava(IVC) dilation and endoluminal stent placement guaded by ultrasonography, including self expanding mental Giaturco stent placement in 33 patients and pure dilation in 3 patients. Portosystemic shunts(PSSs) were followed in 13 patients with hepatic venous occlusion a week after the endoluminal treatment, including splenorenal(S R) shunts in 5 cases,and mesocaval (M C) shunts in 8 cases. Results After endoluminal procedures ,slight heart dysfunction appeared in 3 cases . After shunting ,acute pancreatitis occurred in 1 case, and upper gastrointestinal hemorrhage occurred and finally resulted in death in another case on the 10th day after PSS.All the 36 patients were followed up for 1 month to 8 years. Restenosis of the distal part of stent was found in 1 case 2 years after the operation,hepatic vein occlusion occurred in 1 case 1 year after the treament, hepatoma occurred in 1case 3 years after the treatment,and 1 patient died of C type hepatitis a year later; and 2 cases with infertility had babies 1 year later. All patients had no stent migration or occlusion of shunts .Conclusions Endoluminal therapy guarding by ultrsonography is a convenient, safe and effective method for Budd Chiari syndrome. For patients with hepatic venous occlusions, a portosystemic shunt is recommended.The above mentioned methods provide a feasible and effective means for some kinds of Budd Chiari syndrome.
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Objective To elucidate the clinicopathological characteristic, differential diagnosis, treatment and prognosis of systemic amyloidosis. Methods An inpatient diagnosed as systemic amyloidosis was analyzed for clinical and pathological features as well as laboratory findings. The related literature was reviewed. Results The patient was confirmed to have amyloidosis of the muscle. Muscle involvement was the most prominent and first manifestation, and the patient had widespread visceral involvements, which included cardiovascular system, kidney, respiratory as well as gastrointestinal tracts and tongue. The biopsy of the muscle, mucosa of stomach and intestine, and cutaneous tissue revealed amyloid material deposited in the skeletal and smooth muscle as well as vessel walls. Conclusion Amyloid myopathy is a rare manifestation in systemic amyloidosis. Skeletal muscle weakness and stiffening may be an important clue to the diagnosis of systemic amyloidosis.
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Objective:To explore the pharmacological basis of clinical application of Dachaihu Decoction. Methods: The relevant relation between cilnical features of Dachaihu Decoction and its pharmacological actions are analysed. Results: The various clinical curative effects rest on its relevant pharmacological actions.Conclusion: The good clinical curative effects will be achieved according to Dachaihu Decoction.
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In this paper, a strain of Thiobacillus denitrificans was isolated from soil The optimal pH for growth was 7 0 In mixed cultivation with SRB, the number of SRB was determined The results show that Thiobacillus denitrificans can restrain the growth of SRB, and decrease the concentration of corrosive metabolic production caused by SRB The corrosion rate reduces as a result So it is propitious to prevent and cure the corrosion caused by SRB