Hypomagnesemia � An overlooked parameter in type 2 diabetes mellitus

Background: Diabetes Mellitus refers to a group of common metabolic disorders that share the phenotype of Hyperglycemia. It is the leading cause of morbidity and mortality throughout the world with an estimated worldwide prevalence of 439 million by 2030 and 19% of world抯 DM patients are Indians. Magnesium is an important co-factor for various enzymes involved in Insulin secretion and is involved in sodium-potassium ATPase pump. 25%-38% of Type 2 DM patients had Hypomagnesemia, which has also contributed in developing microvascular complications such as Diabetic Retinopathy (DR) and Diabetic Nephropathy (DN). Various studies have suggested that Magnesium supplementation in Type 2 DM patients with Hypomagnesemia have shown beneficial effects on insulin sensitivity and glucose metabolism. Aim and objectives: To study the prevalence of Hypomagnesemia in Type 2 DM patients and to study the association of Hypomagnesemia with microvascular complications such as DR and DN. Materials and methods: It is a hospital based Observational study carried out in 2022 for a period of 1 year including 60 patients fulfilling the ADA criteria for diagnosing T2DM and patients with Diabetic Retinopathy and Diabetic Nephropathy, and excluding patients with Malabsorption, Chronic diarrhoea, Renal Failure on diuretic therapy, Sepsis, Pancreatitis. Serum Magnesium levels of 1.6 mg/dl � 2.6 mg/dl is considered as normal range. Serum Magnesium were measured using Xylidyl blue colorimetric method. Results: The Mean age of the patients in our study was 55.89 years. Among 60 patients diagnosed with Diabetes Mellitus, 42 patients had Hypomagnesemia, 18 patients had Normomagnesemia (p- value: <0.0001). Patients with an HbA1c levels > 7% had Hypomagnesemia when to compared to patients with HbA1c <7% with a significant p value of 0.009. Hypomagnesemia was also associated with Diabetic Retinopathy and Diabetic Nephropathy with a significant p-value of 0.013 and 0.009 respectively. Conclusion: In our study, it has shown that patients with uncontrolled T2DM had Hypomagnesemia, which is also associated with micro-vascular complications of T2DM such as DR and DN.

Effects of Intestinal Flora and Local Renin-angiotensin System on Diabetic Nephropathy and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Diabetic nephropathy （DN） is a common clinical complication of diabetes， the main cause of end-stage renal disease （ESRD）， and a key determinant of survival in diabetic patients. The pathogenesis of DN is complex， and it is currently believed to be associated with hemodynamic abnormalities， intestinal flora disturbances， glucose and lipid metabolism disorders， oxidative stress， genetic susceptibility， and protein non-enzymatic glycosylation. The local renin-angiotensin system （RAS） has always been the core of the pathogenic and progressive changes of DN. Once activated， it will induce the massive release of oxygen free radicals in the blood vessels， damage the endothelial function， and affect the microcirculation of the body. The recent studies demonstrate that intestinal flora and its metabolites may affect the occurrence and development of DN by activating or antagonizing the local RAS. Compared with western medicine treatment， traditional Chinese medicine （TCM） has the advantages of multiple targets and little toxic and side effects. Many TCM scholars have found that single herbs， their active ingredient extracts， and TCM compound prescriptions can improve kidney function by regulating the local RAS or intestinal flora. Specifically， the Chinese medicinal materials tonifying spleen （Codonopsis Radix， Dioscoreae Rhizoma， Atractylodis Macrocephalae Rhizoma， and Poria）， replenishing kidney （Rehmanniae Radix Praeparata， Corni Fructus， and Pseudostellariae Radix）， and activating blood， resolving stasis， and dredging collaterals （Hirudo， Salviae Miltiorrhizae Radix et Rhizoma， and Angelicae Sinensis Radix） have the regulatory effect. This article summarizes the roles of intestinal flora and local RAS in the occurrence and development of DN， and analyzes the animal experiments or clinical trials of TCM intervention in DN in recent years， aiming to provide more therapies and a theoretical basis for the treatment of DN with integrated TCM and Western medicine.

Eucommia lignans alleviate the progression of diabetic nephropathy through mediating the AR/Nrf2/HO-1/AMPK axis in vivo and in vitro / 中国天然药物

Lignans derived from Eucommia ulmoides Oliver (Eucommia lignans) inhibit the progression of inflammatory diseases, while their effect on the progression of diabetic nephropathy (DN) remained unclear. This work was designed to assess the function of Eucommia lignans in DN. The major constituents of Eucommia lignans were analyzed by UPLC-Q-TOF-MS/MS. The binding between Eucommia lignans and aldose reductase (AR) was predicted by molecular docking. Eucommia lignans (200, 100, and 50 mg·kg-1) were used in model animals to evaluate their renal function changes. Rat glomerular mesangial cells (HBZY-1) were transfected with sh-AR, sh-AMPK, and oe-AR in the presence of high glucose (HG) or HG combined with Eucommia lignans to evaluate whether Eucommia lignans affected HG-induced cell injury and mitochondrial dysfunction through the AR/Nrf2/HO-1/AMPK axis. Eucommia lignans significantly attenuated the progression of DN in vivo. Eucommia lignans notably reversed HG-induced upregulation of inflammatory cytokines and mitochondrial injury, while downregulating the levels of Cyto c, caspase 9, AR, and NOX4 in HBZY-1 cells. In contrast, HG-induced downregulation of Nrf2, HO-1 and p-AMPKα levels were abolished by Eucommia lignans. Meanwhile, knockdown of AR exerted similar therapeutic effect of Eucommia lignans on DN progression, and AR overexpression reversed the effect of Eucommia lignans. Eucommia lignans alleviated renal injury through the AR/Nrf2/HO-1/AMPK axis. Thus, these findings might provide evidence for the use of Eucommia lignans in treating DN.

Comparative Study Of Dry Needling V/S Transcutaneous Electrical Nerve Stimulation In The Treatment Of Hamstring Strain In Football Players

Background:Myofascial pain syndrome is defined as sensory, motor and autonomic symptoms that are caused trigger points (MTrP). It is defined as a hyperirritable spot in skeletal muscle, which is associated with hypersensitive palpable nodule in a taut band. Objectives: Present study was undertaken to add on to available treatment methods for myofascial Trigger points and to find out the effectiveness of dry needling and Transcutaneous Electrical Nerve Stimulation (TENS) therapy for treating myofascial trigger point. Material And Methods:In this study, 32 participants were recruited based on inclusion and exclusion criteria. Dry Needling and TENS therapy was administered to them for a period of 2 weeks, 6 sessions in 2 weeks. Pre and post assessme nt were taken using following outcome measures-Pain Pressure Threshold, Numerical Pain Rating Scale (NPRS), Functional Assessment Scale for Acute Hamstring Injuries (FASH)Result:There was significant decrease in Pain due to hamstring injury on NPRS, agility score and increase in Pain Pressure threshold in patients which is suggestive of decrease in pain and improve functional independency. The outcome of Pressure Algometer, Agility score and NPRS were statistically analyzed. It was found to be effective with significant P value<0.000. Conclusion:Statistically both Dry Needling and TENS are competent enough to alleviate pain but clinically TENS having better response in pain depletion and in increase in functional independency compared to Dry Needling.

Internal Transcribed Spacer (ITS) regions: A powerful tool for analysis of the diversity of wheat genotypes

Wheat is a widely cultivated crop and it is one of the major food sources worldwide. Among the various tools used to study diversity of wheat species, the internal transcribed spacer (ITS) assessment emerges to be the more appropriate approach. In the present study, we evaluated 15 genotypes of Iranian wheat cultivars (wild, native, and breed) using ITS gene sequences. Similarity matrices and dendrogram of phylogenic relationship were constructed using Mega ver6 software. We report the major nucleotide changes in the same position between diploid and hexaploid species. dN/dS ratio for diploid, tetraploid, and hexaploid species indicated a pure selection in the examined gene, with no key changes in the genes, and 91% ITS diversity within individual wheat was evident. The results suggest that as evolution moves forward, nucleotide changes are reduced so that only a few changes in nucleotides occur. ITS marker can distinguish different wheat genotypes at the genomic level and thus prove to be the most appropriate assessment tool for analyzing inter and intra-species relationships.

PK2/PKR1 signaling pathway participates in geniposide protection against diabetic nephropathy in mice / 中国中药杂志

This study aimed to investigate the effects of geniposide(GP) on the expression of prokineticin(PK2) and prokineticin receptor 1(PKR1) in db/db mice with diabetic nephropathy(DN), so as to explore how the PK2 signaling pathway participated in the pathological changes of DN and whether GP exerted the therapeutic effect through this signaling pathway. Male mice were randomly divided into four groups, namely db/m, db/db, db/db+GP, and db/m+GP groups, with five in each group. The mice in the db/db+GP and db/m+GP groups were gavaged with 150 mg·kg~(-1) GP for eight successive weeks. Afterwards, all the mice were sacrificed and the renal tissues were embedded. The morphological changes in glomerulus and renal tubules were observed by Masson and PAS staining. The expression levels of PK2, PKR1, and Wilm's Tumor Protein 1(WT_1) in podocytes were detected by immunohistochemistry, and the protein expression levels of PK2 and PKR1 in mouse kidney by Western blot. The morphological results showed serious glomerular and tubular fibrosis(Masson), high glomerular and tubular injury score(PAS), increased glomerular mesangial matrix, thickened basement membrane, exfoliated brush border of renal tubules, decreased WT_1 in glomerular podocytes, and massive loss of podocytes in the db/db group. After administration with GP, the glomerular and tubular fibrosis was alleviated, accompanied by improved glomerular basement membrane and renal tubule brush edge, and up-regulated WT_1. As revealed by further protein detection, in the db/db group, the expression levels of PK2 and PKR1 and p-Akt/Akt ratio declined, whereas the ratio of Bax/Bcl-2 rose. Ho-wever, PKR2 and p-ERK/ERK ratio did not change significantly. After administration with GP, the PK2 and PKR1 expression was elevated, and p-Akt/Akt ratio was increased. There was no obvious change in PKR2, Bax/Bcl-2 ratio, or p-ERK/ERK ratio. All these have demonstrated that GP improves the renal damage in DN mice, and PK2/PKR1 signaling pathway may be involved in such protection, which has provided reference for clinical treatment of DN with GP.

Treatment of Diabetic Nephropathy Based on Theory of Generation and Restriction Among Five Elements / 中国实验方剂学杂志

The theory of generation and restriction among five elements， as one of the basic theories in traditional Chinese medicine （TCM）， reveals that treating disease should focus on the root. Since its first record in Huangdi's Internal Classic （Huang Di Nei Jing）， this theory has been covered in many chapters of Synopsis of the Golden Chamber （Jin Gui Yao Lue） and further developed by physicians of later generations， allowing it to serve as a guide for clinical treatment of various diseases. Diabetic nephropathy （DN） is one of the most common complications of diabetes and also a main risk factor for death and disability by virtue of the long-term disease course and complex symptoms. At present， no specific drug is available in western medicine. Considering the close relationship of its complicated etiology and pathogenesis with the five zang organs， DN treatment should focus not only on the kidney， but also other zang organs. Guided by the theory of generation and restriction among five elements， this article believes that DN mainly results from kidney deficiency combined with spleen deficiency and its dysfunction in regulating the water passage. In addition， the exuberance of heart fire and the failure of liver to govern the free flow of Qi are also responsible for the occurrence of DN. Clinically， the therapeutic methods proposed based on theory of generation and restriction among five elements are recommended for DN treatment after the differentiation of actual manifestations into specific syndromes. Specifically， the method of replenishing Huo to nourish Tu is applicable to DN patients with spleen and kidney yang deficiency， the method of nourishing Shui to moisten Mu to those with liver and kidney yin deficiency， the method of mutual generation between Jin and Shui to those with lung and kidney yin deficiency， the method of banking up Tu to generate Jin to those with lung and spleen Qi deficiency， the method of purging the heart and tonifying the kidney to those with non-interaction between heart and kidney， and the method of banking up Tu to control Shui to those with spleen deficiency and fluid retention. Such timely and effective interventions are conducive to delaying the development of DN to end-stage renal disease （ESRD） and improving the clinical outcomes. This article discusses the application of the theory of generation and restriction among five elements in TCM to DN treatment， aiming to provide a theoretical basis for the future application of such new diagnosis and treatment ideas.

Yiqiyangyin Huoxuetongluo Prescription Reduces Renal Cell Apoptosis in Rats with Diabetic Nephropathy by Inhibiting JAK2/STAT3 Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effect of Yiqiyangyin Huoxuetongluo prescription on janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway and cell apoptosis in rats with diabetic nephropathy （DN）， and to explore the mechanism of its intervention in DN. Method:A total of 100 SD rats were randomly divided into an experimental group （<italic>n</italic>=80） and a normal group （<italic>n</italic>=20）. The DN model was induced by high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） in the experimental group， and confirmed by the pathological changes of kidney tissues in rats （three in each group） observed under light and electron microscopes. The model rats were randomly divided into a model group （normal saline， equal volume）， low-， medium-， and high-dose （5.775， 11.550， and 23.100 g·kg^-1） Yiqiyangyin Huoxuetongluo prescription groups， and an irbesartan group （irbesartan tablets， 0.016 g·kg^-1）. After drug intervention （<italic>i.g</italic>.， once a day for 16 consecutive weeks）， the 24-hour urine total protein （UTP）， serum total cholesterol （TC）， triglyceride （TG）， creatinine （SCr）， and blood urea nitrogen （BUN） levels of the rats were measured. Western blot was used to detect the protein expression of JAK2/STAT3 signaling pathway. Immunohistochemistry was used to determine the protein expression of B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， zonula occludens-1 （ZO-1）， and actinin-4 in rat kidney tissues. Result:Compared with the normal group， the model group exhibited elevated UTP， serum TC， TG， BUN， and SCr levels （<italic>P</italic><0.05）， severe pathological damage of rat kidney tissues， up-regulated expression of phospho-JAK2 （p-JAK2）， phospho-STAT3 （p-STAT3）， and Bax， increased renal cell apoptosis， and diminished expression of Bcl-2， ZO-1， and actinin-4 （<italic>P</italic><0.05）. Compared with the model group， the Yiqiyangyin Huoxuetongluo prescription group and the irbesartan group showed dwindled UTP， serum TC， TG， BUN， and SCr levels （<italic>P</italic><0.05）， relieved pathological damage of rat kidney tissues， down-regulated p-JAK2， p-STAT3， and Bax expression， and up-regulated expression of Bcl-2， ZO-1， and actinin-4 （<italic>P</italic><0.05）. Conclusion:Yiqiyangyin Huoxuetongluo prescription can reduce renal cell apoptosis and improve the prognosis of DN by inhibiting the activation of JAK2/STAT3 signaling pathway.

Effect of Zishenwan on Pyroptosis and Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells in Diabetic Nephropathy Mice / 中国实验方剂学杂志

Objective:To study the efficacy and mechanism of Zishenwan （ZSW） against pyroptosis and epithelial-mesenchymal transition （EMT） of renal tubular epithelial cells in diabetic nephropathy （DN） mice， so as to provide evidence for the treatment of DN with ZSW. Method:The <italic>db/db</italic> mice with spontaneous diabetes were randomly divided into the model group， dapagliflozin （1.0 mg·kg^-1） group， and high-， medium-， and low-dose （6.0， 3.0， 1.5 g·kg^-1） ZSW groups. The non-diabetic <italic>db/m</italic> mice were classified into the normal group. The ones in the model and normal groups were given an equal volume of deionized water by gavage， while those in the other groups were intervened with the corresponding drugs for 12 weeks. The fasting blood glucose （FBG） level was tested at tail vein once every two weeks. The levels of urine albumin-creatinine ratio （ACR）， <italic>β</italic>-N-acetyl-D-glucosaminidase （NAG）， and cystatin C （CysC） were detected once every four weeks. After 12 weeks of administration， the blood sampled from eyeballs was used for measuring the blood urea nitrogen （BUN） and serum creatinine （SCr）. The pathological changes in renal tissues were observed by light microscopy and transmission electron microscopy. The expression of EMT markers in the renal tubular epithelium was analyzed by immunohistochemistry （IHC）. The in situ terminal end-labeling （TUNEL） staining was conducted to analyze the nuclear damage of renal tubular epithelial cells. The protein and mRNA expression levels of EMT markers， nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） inflammasome and pyroptosis-related inflammatory cytokines in renal tissues were separately assayed by Western blot and Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. Result:Compared with the normal group， the model group displayed significantly increased FBG， BUN， serum SCr， ACR， NAG， and CysC （<italic>P</italic><0.01）， impaired renal tissues， altered EMT marker expression intensities and levels （<italic>P</italic><0.01）， and elevated TUNEL-positive rate and protein and mRNA expression levels of pyroptosis-related inflammatory cytokines and NLRP3 inflammasome （<italic>P</italic><0.01）. Compared with the model group， ZSW and dapagliflozin significantly decreased the levels of FBG， BUN， serum SCr， ACR， NAG， and CysC （<italic>P</italic><0.01）， relieved the pathological injuries in renal tissues， changed the EMT marker expression intensities （<italic>P</italic><0.01） and protein and mRNA expression levels （<italic>P</italic><0.05， <italic>P</italic><0.01）， and down-regulated the TUNEL-positive rate （<italic>P</italic><0.01） of renal tubular epithelial cells as well as the protein and mRNA expression levels of pyroptosis-related inflammatory cytokines （<italic>P</italic><0.01） and NLRP3 inflammasome （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:ZSW alleviates DN possibly by inhibiting pyroptosis and EMT in renal tubular epithelial cells.

Outcome of Vitrectomy in Proliferative Diabetic Retinopathy Patients with Diabetic Nephropathy- A Retrospective Study at Tertiary Eye Centre, Telangana State, in South India.

The increase in prevalence of diabetes in India is one of the leading causes of blindness due to micro vascular and macro vascular complications. The complications in retina and kidney are due to damage of small vessels. Studies have shown significant association between diabetic retinopathy and diabetic nephropathy. In our study, we are discussing the complications during intra and post-operative period and also both anatomical and functional outcome in these patients after vitrectomy for proliferative diabetic retinopathy. Both eye and kidney share same vascular pattern. One pre-existing condition can be followed by the other condition due to similar microvascular damage. We wanted to evaluate the outcome of vitrectomy in proliferative diabetic retinopathy patients associated with chronic kidney disease.METHODSThis is a retrospective study done at Sarojini Devi Eye Hospital, Telangana State, South India, over a two-year period from June 2017 to June 2019. Data was collected from old medical records of our institute, from patients who presented to Retina Dept. with various complaints. They were examined in detail, documented and treated based on clinical presentation after clearance from physician. Patients presented with different ocular manifestations like non-resolving vitreous haemorrhage, focal tractional retinal detachment, multi focal tractional retinal detachment like broad based, table top, combined retinal detachment and tractional maculopathy. Patients underwent pars plana vitrectomy with or without silicone oil endotamponade.RESULTSPrognosis in these patients was good only in cases of non-resolving vitreous haemorrhage and focal tractional retinal detachment (47.61%) whereas in cases like multifocal retinal detachment cases outcome was favourable (42.82%) but patients with combined retinal detachment (9.52%) had poor anatomical and visual outcome.CONCLUSIONSManagement of these patients is very difficult when there is severe proliferative diabetic retinopathy with multiple broad vitreo retinal adhesions. Outcome is very poor particularly in patients of severe proliferative diabetic retinopathy associated with chronic kidney disease and coronary artery disease due to intra operative complications

A Retrospective Comparative Study of Del Nido Versus Intermittent St Thomas Hospital Blood Cardioplegia Solutions in Aortic-Mitral Double Valve Replacement

Introduction: It is not uncommon in patients, havingrheumatic mitral and aortic valve disease, to undergo mitralvalve replacement with aortic valve replacement that is,double valve replacement (DVR) operation who oftenhave severe cardiac dysfunction optimized with medicalmanagement before surgery. In this retrospective studywe investigated 60 such patients, who underwent DVRoperation with either conventional cold blood cardioplegiawith St Thomas 2 solution (STH), or del Nido cardioplegia(DN) over five years and compared the effects of the twotypes of cardioplegia during perioperative and postoperativeperiod with simultaneous comparative study betweenchanges of cardiac performances in the patients with largerleft ventricle as compared to those with less enlargedones.Material and methods: For this retrospective study, the dataof 60 patients of DVR over five years, in Medical College,Kolkata, India, were retrieved for study. The cases wereplaced into 2 groups: STH and DN according to cardioplegiaused during DVR. Demographic, echocardiographic, andseveral perioperative and postoperative data of the two groupsof patients, were collected. Differences between perioperativebehaviour between STH and DN groups and post operativechanges in the echocardiographic parameters betweenpredominantly mitral stenosis (MS) and mitral regurgitation(MR) patients, were analyzed.Results: The aortic cross clamp (CC) and cardiopulmonarybypass (CPB) time in both predominant MS and MR patientswas shorter in the DN than the STH groups. There was lessarrhythmia, less inotropic and ventilator support in the DNgroup. There was 10% mortality in the series with majoritybeing in the STH and MR predominant patients. Postoperativeimprovement of LVEF, reduction of LVIDS and LVIDDwere also observed in MS predominant in comparison toMR predominant patients after DVR in both STH and DNgroups.Conclusion: Use of DN has been found to have a betteroutcome and survival when compared to STH cardioplegiasolution. DVR could reversely remodel depressed heartswith relatively smaller LV volume and restore LV functionof relatively smaller LV of predominant MS patients betterin comparison to MR predominant patients with relativelydilated hearts.

Study on the Relationship between Serum Omentin-1 Level and Degree of Kidney Injuryin Patient with Type 2 Diabetic Nephropathy / 现代检验医学杂志

Objective To explore the relationship between serum Omentin-1 level and degree of kidney in juryin patient with type 2 diabetic nephropathy.Methods 100 diabetic patients with suspected DN were devided into two groups:DM (44 cases) and DN (56 cases) group,and by Mogenson,DN group were devided into DN1 (30 cases) and DN2 (26 cases).In addition 80 healthy subjects were selected as control group.HbA1c,BUN,Scr,β2-MG,HOMA-IR and serum Omentin-1 leves were detected by the standard method.Results There were obvious differences of HbA1c,BUN,Scr,β2-MG,HOMA-IR and Serum Omentin-1 levels among DN,DM and NC (F=6.078～16.231,all P＜0.05).Apart of HbA1c and HOMA-IR,others were no differences between DM group and NC group (t=1.421～2.637,all P＞0.05).There were significant differences of these indicators between DN and NC group (t=8.981～26.785,all P＜0.05).DN group was higher significantly than these in DM group (t=6.371～21.673,all P＜0.05),and HbA1c,BUN,Scr and β2-MG levels had no statistical difference between DN1 and DN2 group (t 0.981～1.389,all P＞0.05).HOMA-IR level in DN2 was higher than that in DN1 group,and serum Omentin 1 declined (t=68.451～76.814,all P＜0.01).There were negative correlation between HOMA IR and serum Omentin-1 leves (r=-0.405,P＜0.05).Conclusion Serum Omentin-1 was related to insulin resistance.Serum Omentin 1 in serum may be a role indicator for impairment of renal function for diagnosis of type 2 diabetic nephropathy.

Preliminary study of the dose-proportion relation of Tibetan medicine Siwei Jianghuang Prescription on diabetic nephropathy rats induced by STZ / 中成药

AIM To investigate the dose-proportion relation of Tibetan medicine Siwei Jianghuang Prescription (SJP) for protective effects on diabetic nephropathy (DN),and the underlying mechanism.METHODS Diabetes mellitus rats induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) were randomly divided into model group,metformin support group,and eight SJP groups with dose-proportion variation (with reference to the uniform design method) for corresponding drug administration once a day,for four weeks.Measurement of fasting blood glucose (FBG) by a blood glucose meter,the concentrations of blood urea nitrogen (BUN),uric acid (UA),serum creatinine (SCr) and total protein (TP) by chemical methods,serum transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) by ELISA kits were conducted,the pathological morphology observation and glomerular basement membrane thickness detection by electron microscope were accomplished as well.Principal components analysis (PCA) and multivariate progressive regression analysis (MSRA) were employed to analyze the relationship between the dose-proportion to pharmacodynamics.RESULTS The resultant indexes revealed variant pharmacological improvement in each treatment group.MSRA results showed that the levels of BUN,renal index,FBG,glomerular basement membrane thickness,VEGF,Scr,and UA had correlative relations with a multiple linear or a multiple non-linear in all groups,which regression equation had a statistical significance (P ＜ 0.05);TGF-β1 level and total protein index with the dose-proportion had no linear or non-linear relation,which the regression equation statistical showed non-significance (P ＞ 0.05).In the global optimization comparison around the range of uniform design,the optimal dosage of the rats model was Curcumae Longae Rhizoma ∶ Berberidis dictyophyllae Cortex ∶ Phyllanthi Fructus ∶ Tribuli Fructus =1 ∶ 2 ∶ 1 ∶ 2.CONCLUSION Siwei Jianghuang Prescription shows better therapeutic effects on DN,which may be related to reducing the levels of BUN,renal index,FBG,glomerular basement membrane thickness,VEGF,Scr and UA.

Clinical Value of Serum ANCA, ACLA and β2-MG in Diagnosis of Early Diabetic Nephropathy / 医学研究杂志

Objective To explore the clinical value of serum ANCA (antineutrophil cytoplasmic antibody),and ACLA (anticardiolipin antibodies) combined with β2-MG (β2 microglobulin) in the diagnostis of DN (early diabetic nephropathy).Methods Fifty cases of patients with early diabetic nephropathy treated in our hospital from February 2016 to February 2017 were selected,and 50 normal volunteers were collected,as the observation group and control group.Positive rates of ANCA,ACLA and β2-MG expression of the patients were observed and recorded.The correlation of ANCA,ACLA,β2-MG and DN was explored and analyzed,and ANCA,ACLA,β2-MG and ANCA,ACLA combined with β2-MG diagnostic efficiency were evaluated.Results The positive rates of ACLA,ANCA,and β2-MG antibodies in the observation group were significantly higher than those in the control group (P ＜ 0.05).There was difference in DN incidence in different levels of ANCA,ACLA,β2-MG (P ＜0.05).There was a significant correlation in ACLA,ANCA,β2-MG and myocardial infarction.Combined diagnostic sensitivity ACLA + ANCA + β2-MG was significantly higher than that of pure ACLA,ANCA,β2-MG (P ＜ 0.05).The specificity was lower than that of simple RBP,Hcy and ultrasonic scoring diagnosis.The consistency was higher than that of pure ACLA,ANCA,and β2-MG (P ＜ 0.05).According to the results of ROC curve,the diagnostic efficiency of ACLA + ANCA + β2-MG combined with early diagnosis of DN was significantly better than that of pure ACLA,ANCA and β2-MG.Conclusion Combined use of ACLA + ANCA + and β2-MG can improve diagnostic accuracy of early diabetic nephropathy,which is more effectively than pure ACLA,ANCA,and β2-MG for diagnosis,and it is worthy of clinical promotion.

Autoimmune in diabetes mellitus and diabetic nephropathy / 中国糖尿病杂志

Diabetes mellitus (DM ) was the third largest chronic disease in the world and the number of patients in China ranked first. Diabetic nephropathy (DN ) as one of the most serious complications of DM was the main cause of death in DM patients along with the incidence of DM gradually increasing. The complex pathogenic mechanism of DN was composed of many factors such as the disorder of glucose metabolism ,inflammation and immune response. Under the special environment of the DM , autoimmunity was an important factor for the occurrence and development of DN. Immune cells ,cytokines and autoantibodies influenced each other resulting in impairment of renal function and affected the progression of DN. Further research on the immune related factors in DN and DM has important value for the prevention and treatment of these diseases.

Exosomes:their extraction and its research progress in the diagnosis and treatment of diabetic nephropathy / 国际药学研究杂志

Exosomes are membrane vesicles secreted by various cells containing unique proteins and miRNA from secretory cells.They can reflect the physiological and pathological state of secretory cells,and play an important role in cell-to-cell communica?tion.In recent years,the exosomes have become the focus of research,which brings hope for diseases that can not be treated effective?ly.This review aims to summarize the extraction methods,biological markers of diabetic nephropathy(DN)and the potential of exo?somes as drug carriers,hoping to bring new ideas for future studies on the occurrence and development mechanisms as well as the treat?ment of DN.

Change and Clinical Significance of Peripheral Blood DN Tregs in Patients with Systemic Lupus Erythematosus / 现代检验医学杂志

Objective To study the expression and function of TCRαβ+ CD3+ CD4-CD8-T (Double negative regulatory T cells,DN Tregs) in peripheral blood of Systemic lupus erythematosus (SLE) patients,and investigate their function in pathogenesis of SLE.Methods TCRαβ+ CD4-CD8 T cells were quantified as percentage of total CD3+ T cells in peripheral blood from 20 SLE patients and 20 healthy controls by flow cytometry.Used ELISA to test the cytokine levels (IFN-γ,TNF-α,IL-6,IL-17A) in the plasma of SLE patients.And analyzed the relationship between the percentage of DN Tregs and cytokines levels.Results The ratio of DN Tregs in TCRαβ+ T cells was significantly increased in SLE patients compared to healthy donors (t=3.54,P＜0.01).The levels of IFN-γ,TNF-α and IL-6 in plasma of SLE patients were higher than healthy donors (t=2.824,2.085,2.304,P＜0.05).The frequency of DN Tregs was found to correlate with IFN-γ (r=0.52,P=0.02) but not TNF-α (r=0.17,P=0.16) and IL-6 (r=0.47,P=0.49).Conclusion This study reveals frequency of DN Tregs in peripheral blood of SLE patients was higher than healthy controls,the frequency of DN Tregs was also found to correlate with IFN-γ levels,which means that DN Tregs may play an important role in pathogenesis of SLE.

Paravertebral block for management of acute postoperative pain and intercostobrachial neuralgia in major breast surgery / Bloqueio paravertebral no controle da dor aguda pós-operatória e dor neuropática do nervo intercostobraquial em cirurgia mamária de grande porte

Abstract Background: Several locoregional techniques have been described for the management of acute and chronic pain after breast surgery. The optimal technique should be easy to perform, reproducible, with little discomfort to the patient, little complications, allowing good control of acute pain and a decreased incidence of chronic pain, namely intercostobrachial neuralgia for being the most frequent entity. Objectives: The aim of this study was to evaluate the paravertebral block with preoperative single needle prick for major breast surgery and assess initially the control of postoperative nausea and vomiting (PONV) and acute pain in the first 24 h and secondly the incidence of neuropathic pain in the intercostobrachial nerve region six months after surgery. Methods: The study included 80 female patients, ASA I-II, aged 18-70 years, undergoing major breast surgery, under general anesthesia, stratified into 2 groups: general anesthesia (inhalation anesthesia with opioids, according to hemodynamic response) and paravertebral (paravertebral block with single needle prick in T4 with 0.5% ropivacaine + adrenaline 3 µg mL−1 with a volume of 0.3 mL kg−1 preoperatively and subsequent induction and maintenance with general inhalational anesthesia). In the early postoperative period, patient-controlled analgesia (PCA) was placed with morphine set for bolus on demand for 24 h. Intraoperative fentanyl, postoperative morphine consumption, technique-related complications, pain at rest and during movement were recorded at 0 h, 1 h, 6 h and 24 h, as well as episodes of PONV. All variables identified as factors contributing to pain chronicity age, type of surgery, anxiety according to the Hospital Anxiety and Depression Scale (HADS), preoperative pain, monitoring at home; body mass index (BMI) and adjuvant chemotherapy/radiation therapy were analyzed, checking the homogeneity of the samples. Six months after surgery, the incidence of neuropathic pain in the intercostobrachial nerve was assessed using the DN4 scale. Results: The Visual Analog Scale (VAS) values of paravertebral group at rest were lower throughout the 24 h of study 0 h 1.90 (±2.59) versus 0.88 (±1.5) 1 h 2.23 (±2.2) versus 1.53 (±1.8) 6 h 1.15 (±1.3) versus 0.35 (±0.8); 24 h 0.55 (±0.9) versus 0.25 (±0.8) with statistical significance at 0 h and 6 h. Regarding movement, paravertebral group had VAS values lower and statistically significant in all four time points: 0 h 2.95 (±3.1) versus 1.55 (±2.1); 1 h 3.90 (±2.7) versus 2.43 (±1.9) 6 h 2.75 (±2.2) versus 1.68 (±1.5); 24 h 2.43 (±2.4) versus 1.00 (±1.4). The paravertebral group consumed less postoperative fentanyl (2.38 ± 0.81 µg kg−1 versus 3.51 ± 0.81 µg kg−1) and morphine (3.5 mg ± 3.4 versus 7 mg ± 6.4) with statistically significant difference. Chronic pain evaluation of at 6 months of paravertebral group found fewer cases of neuropathic pain in the intercostobrachial nerve region (3 cases versus 7 cases), although not statistically significant. Conclusions: Single-injection paravertebral block allows proper control of acute pain with less intraoperative and postoperative consumption of opioids but apparently it cannot prevent pain chronicity. Further studies are needed to clarify the role of paravertebral block in pain chronicity in major breast surgery.

Resumo Justificativa: Estão descritas várias técnicas locorregionais para a abordagem da dor aguda e dor crônica após cirurgia de mama. O ideal seria uma técnica fácil de fazer, reprodutível, com pouco desconforto para as doentes, com poucas complicações e que permitirá um bom controle da dor aguda e uma diminuição da incidência de dor crônica, notadamente dor neuropática do intercostobraquial, por ser a entidade mais frequente. Objetivos: Estudar a aplicação de bloqueio paravertebral com picada única no pré-operatório de cirurgia mamária de grande porte. Avaliar numa primeira fase o controle de dor aguda e náuseas-vômitos no pós-operatório (NVPO) nas primeiras 24 horas e numa segunda fase a incidência de dor neuropática na região do nervo intercostobraquial seis meses após a cirurgia. Métodos: Foram incluídas 80 doentes do sexo feminino, ASA I-II, entre 18 e 70 anos, submetidas a cirurgia mamária de grande porte sob anestesia geral, estratificadas em dois grupos: anestesia geral (anestesia geral inalatória com opioides segundo resposta hemodinâmica) e paravertebral (bloqueio paravertebral com picada única em T4 com ropivacaína 0,5% + adrenalina 3 µg/mL com um volume de 0,3 mL/kg pré-operatoriamente e posterior indução e manutenção com anestesia geral inalatória). No pós-operatório imediato foi colocada PCA (Patient-controlled analgesia) de morfina programada com bolus a demanda durante 24 horas. Foram registados fentanil intraoperatório, consumo de morfina pós-operatória, complicações relacionadas com as técnicas, dor em repouso e ao movimento a 0, 1 h, 6 h e 24 h, assim como os episódios de NVPO. Foram analisadas todas as variáveis identificadas como fatores de cronificação da dor idade, tipo de cirurgia, ansiedade segundo escala de HADS (Hospital Anxiety and Depression scale), dor pré-operatória; acompanhamento no domicílio; índice de massa corporal (IMC), tratamentos adjuvantes de quimioterapia/radioterapia e foi verificada a homogeneidade das amostras. Aos seis meses da cirurgia foi avaliada, segundo escala DN4, a incidência de dor neuropática na área do nervo intercostobraquial. Resultados: O grupo paravertebral teve valores de VAS (Escala Visual Analógica) em repouso mais baixos ao longo das 24 horas de estudo 0 h 1,90 (± 2,59) versus 0,88 (± 1,5); 1 h 2,23 (± 2,2) versus 1,53 (± 1,8); 6 h 1,15 (± 1,3) versus 0,35 (± 0,8); 24 h 0,55 (± 0,9) versus 0,25 (± 0,8) com significado estatístico às 0 e às 6 horas. Em relação ao movimento o grupo paravertebral teve valores de VAS mais baixos e com significância estatística nos quatro momentos de avaliação: 0 h 2,95 (± 3,1) versus 1,55 (± 2,1); 1 h 3,90 (± 2,7) versus 2,43 (± 1,9) 6 h 2,75 (± 2,2) versus 1,68 (± 1,5); 24 h 2,43 (± 2,4) versus 1,00 (± 1,4). O grupo paravertebral consumiu menos fentanil (2,38 ± 0,81 µg/Kg versus 3,51 ± 0,81 µg/Kg) e menos morfina no pós-operatório (3,5 mg ± 3,4 versus 7 mg ± 6,4), com diferença estatisticamente significativa. Na avaliação de dor crônica aos seis meses no grupo paravertebral houve menos casos de dor neuropática na região do nervo intercostobraquial (três versus sete) embora sem significância estatística. Conclusões: O bloqueio paravertebral com picada única permite um adequado controle da dor aguda com menor consumo de opioides intraopreatórios e pós-operatórios, mas aparentemente não consegue evitar a cronificação da dor. Mais estudos são necessários para esclarecer o papel do bloqueio paravertebral na cronificação da dor em cirurgia mamária de grande porte.

Research progress of the effect of epithelial-mesenchymal transition on diabetic renal interstitial fibrosis / 中国糖尿病杂志

[Summary] The epithelial‐mesenchymal transition (EMT) is a biological process in which epithelial cells are converted into cells with mesenchymal phenotype in specified physiological and pathological conditions. EM T plays a critical role in proper embryonic development ,tissue regeneration ,cancer metastasis and organ fibrosis. EM T can be divided into three subtypes (Ⅰ ,II and Ⅲ ) based on different biological context ,of which type II EMT contribute importantly to the development of organ fibrosis.Renal interstitial fibrosis (RIF) is an important pathological feature of diabetic nephropathy (DN). The understanding of molecular mechanisms of this process tubular EM T may provide a clue to intervene the development of DN through suppressing EM T and reversing RIF.

Study on the Significance of Detecting MMP-1 0 Level in Patients with Type 2 Diabetic Nephropathy / 现代检验医学杂志

Objective To explore the significance of detecting serum MMP-10 in type 2 diabetic nephropathy.Methods 100 diabetic patients with suspected DN were devided into two groups,that was DM(42 cases)and DN(58 cases)group,and 60 casescontrolgroup(NC).By Mogenson,DN1(30 cases)and DN2(28 cases),HbA1c,BUN,Scr,UAER,β2-MG and MMP-10 leves were detected by the standard method.Results There were obvious differences of HbA1c,BUN,Scr,UAER,β2-MG and MMP-10 levels among DN,DM and NC(P0.05).DN group was higher significantly than these in DM group(P<0.05),and HbA1c,BUN,Scr,UAER, andβ2-MG levels had no statistical difference between DN1 and DN2 group.MMP-10 level in DN2 was higher than that in DN1 group(P<0.05).Conclusion MMP-10 in serum may be a role indicator for impairment of renal function for diagnosis of type 2 diabetic nephropathy.