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ObjectiveTo explore the molecular mechanism of modified Shengjiangsan in alleviating endoplasmic reticulum (ER) stress and reducing urinary protein in the rat model of diabetic nephropathy (DN). MethodSeventy-five SD rats were randomized into normal, model, low-, medium-, and high-dose (4.37, 8.73, 17.46 g·kg-1, respectively) modified Shengjiangsan, and irbesartan (0.014 g·kg-1) groups, with 10 rats in each group. Rats were administrated with corresponding doses of medications or distilled water by gavage, once a day, for 8 consecutive weeks. After the last administration, the levels of glucose (GLU) in the blood, 24-hour urinary protein (24 h-UTP), and superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in the renal tissue were measured. Hematoxylin-eosin staining, periodic acid-Schiff staining, and transmission electron microscopy were employed to observe the pathological changes in rat kidneys. Immunohistochemistry was employed to measure the expression levels of nephrin, podocin, glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and activating transcription factor 4 (ATF4) in the kidneys of rats. Western blot was employed to measure the protein levels of silent information regulator 1 (Sirt1), phosphorylated (p)-protein kinase RNA-like endoplasmic reticulum kinase (PERK), and p-eukaryotic translation initiation factor 2 alpha (eIF2α) in rat kidneys. ResultCompared with the normal group, the modeling caused pathological damage to the kidneys, elevated the levels of GLU and 24 h-UTP (P<0.05), up-regulated the protein levels of GRP78, CHOP, ATF4, p-PERK, and p-eIF2α (P<0.05), and down-regulated the protein level of Sirt1 (P<0.05) in rat kidneys. Compared with the model group, modified Shengjiangsan and irbesartan lowered the GLU and 24 h-UTP levels (P<0.05), alleviated the pathological damage in the renal tissue, down-regulated the protein levels of GRP78, CHOP, ATF4, p-PERK, and p-eIF2α (P<0.05), and up-regulated the protein level of Sirt1 (P<0.05). ConclusionModified Shengjiangsan up-regulates Sirt1 expression and inhibits phosphorylation of proteins in the PERK/eIF2α pathway to reduce ER stress and oxidative stress in the renal tissue, thus alleviating the pathological damage in the renal tissue and reducing urinary protein in DN rats.
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ObjectiveTo observe the effect of salvianolate on the protein expressions of adenosine monophosphate (AMP)-activated protein kinase (AMPK), silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), autophagy and apoptosis in kidney tissue of rats with membranous nephropathy (MN), and to explore its possible molecular mechanism against MN. MethodEighty male SD rats were randomly divided into normal group, model group, benazepril hydrochloride group (10 mg·kg-1), and salvianolate low-, medium-, and high-dose groups (16.7, 33.3 and 66.7 mg·kg-1). The rats were modeled by injection of cationized bovine serum albumin (C-BSA) into the tail vein. After successful modeling, rats in the administration groups were given corresponding doses of drugs for 4 consecutive weeks, and then 24-hour urine, serum and kidney tissue were collected for the detection of 24-hour urinary protein (UTP), blood urea nitrogen (BUN), serum creatinine (SCr), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C reactive protein (CRP), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and malondialdehyde (MDA). The pathological changes of kidneys were observed by light microscope, electron microscope and immunofluorescence. Western blot was used to detect the protein expressions of phospho-AMPK (p-AMPK), AMPK, phospho-SIRT1 (p-SIRT1), SIRT1 and PGC-1α in rat kidney tissue. The protein expressions of autophagy-specific gene (Beclin-1), microtubule-associated protein 1 light chain 3 (LC3) Ⅱ, ubiquitin-binding protein (p62), B cell lymphoma (Bcl-2), Bcl-2-associated X (Bax), and cysteine aspartic protease-7 (Caspase-7) in rat kidney tissue were determined by immunohistochemistry (IHC). ResultCompared with the conditions in the normal group, the levels of UTP, IL-6, TNF-α, CRP and MDA in the model group were increased (P<0.05) while the levels of SOD and GSH-Px were decreased (P<0.05), and there was no difference in BUN and SCr. Compared with the model group, the administration groups had lowered UTP, IL-6, TNF-α, CRP and MDA (P<0.05) while elevated SOD and GSH-Px (P<0.05). It could be seen from hematoxylin and eosin (HE) staining, Masson staining, immunofluorescence and electron microscopy that the pathological damage of rat kidney tissue in the model group was significant, but after treatment with benazepril hydrochloride and salvianolate, the pathological damage of kidney cells was gradually improved. The expressions of p-AMPK/AMPK, p-SIRT1/SIRT1, PGC-1α, Bcl-2, Beclin-1 and LC3Ⅱ in rat kidney in the model group were lower than those in the normal group (P<0.05) while the expressions of Bax, Caspase-7 and p62 were higher (P<0.05). Compared with the model group, benazepril hydrochloride group and salvianolate groups had an up-regulation in the expressions of p-AMPK/AMPK, p-SIRT1/SIRT1, PGC-1α, Bcl-2, Beclin-1 and LC3Ⅱ in the kidney (P<0.05) while a down-regulation in the expressions of Bax, Caspase-7 and p62 (P<0.05). ConclusionThe protective effect of salvianolate on the kidneys of MN rats may be related to the activation of AMPK/SIRT1/PGC-1α signaling pathway, the up-regulation of autophagy and the reduction of apoptosis.
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Objective:To analyze the rules of medication and principles of formulas for the treatment of coronavirus disease 2019 (COVID-19) using the traditional Chinese medicine inheritance support platform (V2.5).Methods:The clinical data, including gender, age, clinical symptoms, frequency of traditional Chinese medicine medication and prescription information, of patients with COVID-19 and asymptomatic infection who were admitted to Hebei COVID-19 designated hospital supported by medical team of First Affiliated Hospital of Hebei University of Chinese Medicine from January to March 2021 were collected. The information data were input into the traditional Chinese medicine inheritance support platform (V2.5). The data mining and analysis were realized by the integrated association rules and complex entropy clustering analysis methods of the software, including the analysis of the frequency of each drug use, drug meridian, taste, and prescription rules, and the new prescriptions were developed.Results:A total of 564 patients (564 prescriptions) were enrolled, involving 200 Chinese herbs, including 357 cases of common COVID-19 and 207 cases of asymptomatic infection. The proportion of women with common COVID-19 was high, and the high incidence age group was 51-70 years old. There was no significant difference in gender of asymptomatic infection, and the high incidence age group was 1-20 years old. The main clinical manifestations of most patients were head heavy and cough, followed by low fever and cough with sputum, the main tongue coating and pulse pattern were similar in both types of patients. The frequency of traditional Chinese medicine used in patients with common type of COVID-19 from high to low was liquorice root (326 times), indian bread (264 times), pinellia tuber (263 times), bitter apricot seed (236 times), baical skullcap root (229 times), gypsum (205 times), agastache rugosus (201 times), dried tangerine peel (194 times), ephedra (184 times), and Chinese thorowax root (163 times), while that used by asymptomatic infection were baical skullcap root (174 times), liquorice root (142 times), medicated leaven (137 times), agastache rugosus (127 times), pinellia tuber (114 times), Chinese thorowax root (100 times), officinal magnolia bark (91 times), atractylodes rhizome (89 times), peony root (84 times), and milkvetch root (83 times). The two types of patients were mainly treated with warm, cold and flat drugs, and the nature and taste were mainly pungent, bitter and sweet. The meridian tropism of drugs was mainly lung, spleen and stomach. High frequency drug formulation mainly included drugs for resolving turbidity and detoxification. At the same time, seven new prescriptions for common COVID-19 and four new prescriptions for asymptomatic infection were developed.Conclusions:The primary reason for the COVID-19 occurrence and development is turbidity-toxin and the qi of plague, and resolving turbidity and detoxication are the basic treating principle. On the basis, for patients with common COVID-19, symptomatic treatment such as relieving exterior syndrome, clearing heat, resolving phlegm, and antitussive drugs should be taken into account at the same time, while the treatment of asymptomatic infections should focus more on supporting the body and eliminating the harmful pathogens.
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[Objective]To assess the accuracy and value of radiographic technique using computed tomography(CT) measurements in cadaveric specimens during anterior cervical corpectomy in order to define the safe lateral limit of dissection.[Method]The gutter of C4~6 corpectomy on 5 cadaveric samples was filled with radioopaque dye.An antero-posterior X-ray was used to measure the narrowest distance from dye column to the line of uncovertebral joints.A CT scan confirmed the distance from the borderline of the gutter to vertebral arteries.[Result]The distance between the X-ray dye column and the line of uncovertebral joints averaged 4.7 mm in the left and 4.2 mm in the right.While the distance from the borderline of the gutter to vertebral arteries with CT scan averaged 6.1 mm in the left and 5.9 mm in the right.The measured distance by radiographic technique underestimated the true distance.[Conclusion]Intraoperative radiographic technique can estimate the lateral distance between the gutter of corpectomy and vertebral arteries by measuring the distance from the dye column to the line of uncovertebral joints.This technique provides surgeons an additional margin of safety during anterior cervical corpectomy.
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Objective To analyse correlated risk factors of evolving cerebral infarction(ECI).Methods The follow data was recorded in the acute cerebral infarction (ACI)cases when they were admitted :sex,age,systolic blood pressure(SBP),diastolic blood pressure(DBP),history of disease (diabetes mellitus,hypertension,hyperlipidaemia,cerebral infarction,hyperuricemia or smoking).The following examinations or determinations were done,including:white blood cell count (WBC),platelet count (PLT),blood gluconate(GLU),PT-INR,fibrinogen(FG),TT-INR,APTT-INR,C-reactive protein(CRP),D-dimer(D-D),products of fibrin degradation(FDP),anti-thrombin Ⅲ(ATⅢ),apolipoprotein A(apoA),apolipoprotein B(apoB),blood urea nitrogen(BUN),creatinine(CR),triglyceride (TG),high density lipoprotein (HDL),low density lipoprotein (LDL),very low density lipoprotein (VLDL),GOT,lactate dehydrogenase(LDH),creatine phosphokinase (CPK),MB isoforms of creatine phosphokinase (CPK-MB),? hydroxybutyrate dehydrogenase (?-HBDH),troponin I(TnI),cerebral CT or MRI and carotid ultrasonography.The patients were divided into two groups,ECI and completed cerebral infarction (CCI),according whether neurons function scale deteriorated.When cases of both groups exceeded 50,we took statistic test by SPSS10.0 statistic software.Results 8 of the above 46 markers had significant defference between the two groups,including CRP,WBC,apoB,GLU,LDH,CPK-MB,?-HBDH and DBP.ECI was more common in patients who had lower DBP or higher CRP,WBC,apoB,GLU,LDH,CPK-MB,?-HBDH when they were admitted.Conclusion The increase of CRP,WBC,apoB,GLU,LDH,CPK-MB,?-HBDH or decrease of DBP when patients are admitted can be predictive markers of ECI.