Evaluation of G3BP1 in the prognosis of acute and acute-on-chronic liver failure after the treatment of artificial liver support system

BACKGROUND The increased expression of G3BP1 was positively correlated with the prognosis of liver failure.AIM To investigate the effect of G3BP1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver failure(ACLF)after the treatment of artificial liver support system(ALSS).METHODS A total of 244 patients with ALF and ACLF were enrolled in this study.The levels of G3BP1 on admission and at discharge were detected.The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis.RESULTS This study was shown that lactate dehydrogenase(LDH),alpha-fetoprotein(AFP)and prothrombin time were closely related to the prognosis of patients.After the ALSS treatment,the patient’amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission(difG3BP1)<0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index.The subgroup analysis showed that the difG3BP1<0 group had a higher risk of progression,regardless of model for end-stage liver disease high-risk or low-risk group.At the same time,compared with the inflam matory marks[tumor necrosis factor-α,interleukin(IL)-1βand IL-18],G3BP1 had higher discrimination and was more stable in the model analysis and validation set.When combined with AFP and LDH,concordance index was respectively 0.84 and 0.8 in training and validation cohorts.CONCLUSION This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS.The combination of G3BP1,AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.

The Relationship between Psychological Vulnerability,Aging Attitudes and Life Meaning in Elderly Patients with Comorbidities

Background:With the rapid aging of China’s population and the increasing prevalence of comorbidities in the elderly,psychological crises have become more common.This study aims to investigate the present status of psychological vulnerability,aging attitudes,and life meaning in elderly patients with comorbidities.Methods:A total of 685 elderly inpatients and outpatients at Renmin Hospital of Wuhan University between July and December 2022 were selected using the simple random sampling method.Social demographic data were collected,and the Attitudes to aging Questionnaire(AAQ),the Chinese Life Meaning Questionnaire(C-MLQ),and the Psychological Vulnerability Scale(C-PVS)were used for the analysis.A total of 685 questionnaires were received,and 602 valid questionnaires were collected,with an effective rate of 87.88%.Data analysis was performed using SPSS V25.0 and AMOS V24.0.Results:The total scores of psychological vulnerability,aging attitudes,and life meaning were 69.4±12.8,80.2±13.5 and 39.2±8.3,respectively.The psychological vulnerability was significantly negatively correlated with life meaning and aging attitudes(r=-0.351,-0.264;p<0.01).There was a significant positive correlation between aging attitudes and life meaning(r=0.515;p<0.01).Life meaning played a partial mediating role between psychological vulnerability and aging attitudes(β=3.070,p<0.05).Conclusion:This study found that the psychological vulnerability in elderly patients with comorbidities was at the lower level,which was related to the elderly patients’aging attitudes and their current status of life meaning.The level of psychological vulnerability in elderly patients with senile-related comorbidities needs to be further improved.Medical workers should pay attention to the psychological vulnerability of elderly patients and improve the identification of psychological crises of such patients.

Effects of Lanthanum Carbonate on Vascular Calcification in Elderly Maintenance Hemodialysis Patients

Summary： The effect of lanthanum carbonate on abdominal aortic calcification （AAC） in the elderly maintenance hemodialysis （MHD） patients was investigated. Fifty-four cases subjected to routine MHD complicated with skin pruritus admitted to our hospital were selected and randomly divided into case group （n=28） and control group （n=26）. The control group was given routine MHD alone. The case group was given lanthanum carbonate additionally on the basis of routine MHD. The changes of itching degrees at first and third month, and serum calcium, phosphorus, calcium-phosphorus products, intact parathyroid hormone （iPTH） levels and AAC scores at third month after treatments were compared be- tween the two groups. The correlation between calcium-phosphorus products and AAC scores was also analyzed. There was no significant difference in the baseline of blood urea nitrogen （BUN）, serum creatinine （Scr）, uric acid, albumin, hemoglobin, C reactive protein （CRP）, low density lipoprotein （LDL）, high density lipoprotein （HDL）, triglyceride, total cholesterol between case group and control group （P〉0.05 for all）. There was also no significant difference in the baseline itching scores between the case group and the control group （P〉0.05）. At 1st and 3rd month after treatment, the itching scores in the case group were 14.2±3.2 and 10.5±2.3, respectively, which were significantly lower than the baseline and those in the control group （P〈0.05 for all）. At 1 st and 3rd month after treatment, the itching scores in the control group were 23.6v5.9 and 24.8±6.3, respectively, which were significantly higher than the baseline （P〈0.05）. There was no significant difference in the baseline of serum calcium, phos- phorus, calcium-phosphorus products, iPTH levels between the case group and control group （P〉0.05）. At 3rd month after treatment, serum phosphorus, calcium-phosphorus products and iPTH levels in the case group were decreased significantly as compared with the baseline （P〈0.05）, and the serum calcium, phosphorus, calcium-phosphorus products, and iPTH levels were statistically decreased as compared with those in the control group （P〈0.05）. The AAC scores showed statistically significant difference between the case group and the control group （P〈0.05）. The serum phosphorus and AAC scores showed a positive correlation in both two groups. It was suggested that the administration of lanthanum carbon- ate in the elderly MHD patients can effectively relieve itching, and simultaneously reduce serum phos- phorus and iPTH levels, resulting in the attenuation of vascular calcification.

Superiority of Laparoscopy in the Peritoneal Dialysis Catheter Reset Surgery

Peritoneal dialysis catheter surgery has been used in clinical treatment for nearly 40 years, and open surgery under local anesthesia is the conventional method. However, catheter displacement after open surgery is still the thorny issue during our clinical practice. Then the reset surgery is often required to be taken again. Nowadays, laparoscopic peritoneal dialysis catheter draws our attention due to its advantages of accurate positioning, smaller incision, and less pain, and its clinical application has been limited. While laparoscopic surgery is recognized, there are few relevant studies on whether there is difference during the catheter reset process between the two surgical approaches. In this study, we mainly discussed the rate of secondary catheter migration, the incidence of complications after catheter reset for two surgical approaches and the hospital stay as well as the total clinical cost for the two surgical approaches. In this study, we retrospectively analyzed 25 cases of end-stage renal disease, who received catheterization for peritoneal dialysis and regular peritoneal dialysis in our hospital from March 2010 to December 2013, and had a medical history of catheter migration. We collected the relevant clinical data for all patients. Fifteen patients selected laparoscopic catheter reset, and 10 patients selected the traditional surgical method for catheter reset by themselves. For all patients enrolled, we analyzed the incidence of secondary catheter migration and postoperative complications, hospitalization time, and total cost for different methods of reset. Through the studies above, we found that laparoscopic peritoneal dialysis catheter surgery offered accurate catheter location and a small incision that was easy to heal. Besides, the incidence of postoperative complications for the laparoscopic surgery was lower than that for traditional surgical approach for catheter reset. The average hospitalization time for laparoscopic surgery was shorter than that for the traditional surgical approach. The total cost of laparoscopic surgery was more than that of the traditional surgery. Therefore, the rational application of a laparoscopic peritoneal dialysis catheter and reset surgery can increase the success rate of peritoneal dialysis, reduce the complications, shorten hospitalization time of patients, and thus enhance patient＇s confidence to stick it out.

Clinicopathologic analysis of IgA nephropathy patients with anemia

Objective:To explore the clinicopathological characteristics of IgA nephropathy(IgAN)patients with anemia.Methods:The clinical and pathological data of patients diagnosed with primary IgAN at the Renmin Hospital of Wuhan University from January 2017 to December 2019 were colleted.The patients were divided into anemia group and without anemia group based on the pressure value when performing the Kidney kidney biopsy.Compare the data of the two groups of patients.Results:A total of 314 subjects were enrolled,including 181 females(57.64%),and the female-male ratio was 1.36∶1.Their age was(37±13)years.There were 113 patients(35.99%)in anemia group,201 cases(64.01%)in non-anemic group.Univariate analysis showed that compared with non-anemia group,anemia group had higher serum creatinine and 24h urine protein levels,higher proportion of females and eGFR<60 ml·min^(-1)·(1.73m^(2))^(-1),lower serum albumin,higher proportion of tubular atrophy/interstitial fibrosis(T1/2),endothelial cell proliferation(E1)and crescent formation(C1/2),which were statistically significant(all P<0.05).Anemia group had a higher proportion of Ⅳ~Ⅴlevel in Lee's classification.There was a difference in Lee's grading composition between the two groups,and the difference was statistically significant(P<0.01).Spearson correlation analysis showed that the glomerular and tubulointerstitial lesions were negatively correlated with serum hemoglobin、albumin and eGFR,but positively corelated with proteinuria(P<0.05).Multivariate Logistic regression analysis found that decreased serum albumin level,increased serum creatinine and hypertension were independent risk factors for anemia in IgAN patients.Conclusions:Anemia can aggravate the pathological damage and clinical manifestations in patients with IgA nephropathy.The anemia must be corrected in time during treatment and follow-up.At the same time.it should be paid more attention to the changes of serum albumin level,blood pressure monitoring and the protection of renal function.

Carbamylated Erythropoietin Alleviates Kidney Damage in Diabetic Rats by Suppressing Oxidative Stress

The oxidative stress response plays an important role in the occurrence and development of diabetic kidney disease(DKD).It has become a new treatment target for DKD.In the current study,the effects of carbamylated erythropoietin(CEPO)on renal oxidative stress and damage in diabetic rats were examined.Thirty Sprague Dawley rats were intraperitoneally administered with 60 mg/kg streptozotocin to establish the diabetes model.The diabetic rats were randomly allocated into 4 groups(n=6 each):diabetes model group(DM group),DM+CEPO treatment group(DC group),DM+CEPO+EPO receptor(EPOR)blocking peptide treatment group(DCEB group),and DM+CEPO+CD131 blocking peptide treatment group(DCCB group).Meanwhile,a normal control group(NC group,n=6)was set up.Kidney tissues and blood samples were obtained for evaluation of oxidative stress and renal function.The results showed that diabetic rats exhibited increased oxidative stress in the kidney and early pathological changes associated with DKD.Treatment with CEPO reduced oxidative stress and attenuated renal dysfunction.However,diabetic rats treated with the combination of CEPO and EPOR blocking peptide or CD131 blocking peptide showed increased oxidative stress and reduced renal function when compared with CEPO treatment alone group.These results suggested that CEPO can protect against kidney damage in DKD by inhibiting oxidative stress injury via EPOR-CD131 heterodimers.

Induction of lupus-like renal damages by double stranded DNA derived from Trypanosoma equiperdum

Lupus nephritis is the most common visceral complication in the patients with systemic lupus erythematosus （SLE）.It was evident that the anti-dsDNA antibodies were closely related to lupus nephritis, as seen in patients who had higher titers of serum anti-dsDNA antibodies had more severe renal lesions and even worse prognosis. So far it is still unknown how the dsDNA or anti-dsDNA antibody plays a role in the pathogenesis of lupus nephritis. The Trypanosoma equiperdum （TE） has uniformed dsDNA, no histone is found in both the cell nucleus and kinetonucleus. For this reason, TE became an optimal substrate used for detecting anti-dsDNA antibodies in SLE patients. It is proved that TE substrate is highly sensitive and specific. This reminds us to concern whether TE dsDNA share same SLE antigenic determinants with the pathogenic dsDNA in patients. Compared to the mammalian dsDNA, the kinetoplast DNA （kDNA） of TE has simpler molecular structure which makes it easier for purification. It offers us the possibility to establish lupus-like nephritis model by TE kDNA. We subcutaneously injected TE kDNA into normal mice. The result indicated lupus-like nephritis has been successfully induced by this simple and convenient protocol, which is useful to elucidate the particular role of dsDNA or anti-dsDNA antibody in lupus nephritis.

Darbepoetin alfa injection versus epoetin alfa injection for treating anemia of Chinese hemodialysis patients with chronic kidney failure:A randomized,open-label,parallel-group,non-inferiority Phase III trail

Background:Erythropoietin is a glycoprotein that mainly regulates erythropoiesis.In patients with chronic renal failure with anemia,darbepoetin alfa can stimulate erythropoiesis,correct anemia,and maintain hemoglobin levels.This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections(Recombinant Human Erythropoietin injection,rHuEPO)when maintaining hemoglobin(Hb)levels within the target range(10.0-12.0 g/dL)for the treatment of renal anemia.Methods:Ninety-five patients were enrolled in this study from April 15,2013 to April 10,2014 at 25 sites.In this study,patients(n=95)aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group(n=56)and a twice or three times per week intravenous epoetin alfa group(n=39)for 28 weeks,who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease(CKD)and were undergoing hemodialysis or hemofiltration with ESA-naive(erythropoiesis stimulating agent-naive).The primary efficacy profile was the mean Hb level(the non-inferiority margin was-1.0 g/dL,week 21-28);the secondary efficacy profiles were the Hb increase rate(week 0-4),the target Hb achievement cumulative rate and time,the change trends of the Hb levels,and the target Hb maintenance ratio.Adverse events(AEs)were observed and compared,and the efficacy and safety were analyzed between the two treatment groups.Additionally,the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period.SAS?software version 9.2 was used to perform all statistical analyses.Descriptive statistics were used for all efficacy,safety,and demographic variable analyses,including for the primary efficacy indicators.Results:The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group,respectively;the difference of the lower limits of the 95%confidence intervals(CI)between the two groups was 0.1 g/dL(>-1.0 g/dL),and non-inferiority was proven;the Hb levels started to increase in the first four weeks at a similar increase rate;no obvious differences were observed between the groups in the target Hb achievement cumulative rates,and the Hb levels as well as the target Hb level maintenance rate changed over time.The incidence of AEs was 62.5%in the darbepoetin alfa group and 76.9%in the epoetin alfa group.All the adverse events observed in the study were those commonly associated with hemodialysis.Conclusion:Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well,which makes it not inferior to epoetin alfa intravenously twice or three times per week.Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection for the treatment of renal anemia in Chinese hemodialysis patients:A randomized,open-label,parallel-group,noninferiority phase III trial

Background:This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection(recombinant human erythropoietin injection,rHuEPO)for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method:This study was a multicenter,randomized,open-label,intergroup parallel control phase III noninferiority trial from April 19,2013 to September 9,2014 at 25 sites.In this study,the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks.The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week.All subjects underwent epoetin alfa administration during the 8-week baseline period.After that,subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group.The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period(noninferiority threshold:-1.0 g/dl)was tested between the two treatments.The time-dependent hemoglobin(Hb)concentration and the maintenance rate of the target Hb concentration(the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl)were also evaluated.Iron metabolism,including changes in the serum iron,total iron-binding capacity,ferritin,transferrin saturation,and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further.Adverse events(AEs)were also observed and compared,and the safety was analyzed between the two treatment groups.The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed.SAS?software version 9.2 was used to perform all statistical analyses.Descriptive statistics were used for all efficacy,safety,and demographic variable analyses,including for the primary efficacy indicators.Results:Four hundred and sixty-six patients were enrolled in this study,and ultimately 384 cases were analyzed for safety,including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group.There were 211 cases in the per-protocol set,including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group.The changes in the average Hb concentrations from the baseline to the end of the evaluation period were-0.07 and-0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively.The difference between the two groups was 0.08 g/dl(95%confidence interval[CI]:-0.22 to 0.39),and the lower limit of the 95%CI was-0.22>-1.0 g/dl.The average Hb concentrations of the two groups were 10.88-11.43 g/dl(darbepoetin alfa)and 10.91-11.38 g/dl(epoetin alfa)during the study period of Weeks 0-28,with the maintenance rates of the target Hb concentration ranging within 71%-87%and 78%-95%in the darbepoetin alfa group and epoetin alfa group respectively.During the period of comparison between the two groups,the incidence of AEs in the darbepoetin alfa group was 61.42%,while in the epoetin alfa group it was 56.41%.All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion:The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Dihydroartemisinin attenuates ischemia/reperfusion-induced renal tubular senescence by activating autophagy

Acute kidney injury(AKI)is an important factor for the occurrence and development of CKD.The protective effect of dihydroartemisinin on AKI and and reported mechanism have not been reported.In this study,we used two animal models including ischemia-reperfusion and UUO,as well as a high-glucose-stimulated HK-2 cell model,to evaluate the protective effect of dihydroartemisinin on premature senescence of renal tubular epithelial cells in vitro and in vivo.We demonstrated that dihydroartemisinin improved renal aging and renal injury by activating autophagy.In addition,we found that co-treatment with chloroquine,an autophagy inhibitor,abolished the anti-renal aging effect of dihydroartemisinin in vitro.These findings suggested that activation of autophagy/elimination of senescent cell might be a useful strategy to prevent AKI/UUO induced renal tubular senescence and fibrosis.