Abstract Background At present, estimated glomerular filtration rate (eGFR) remains the most frequently utilized parameter in the evaluation of kidney injury severity. Numerous equations have been formulated based on serum creatinine (Scr) or serum cystatin C (Cysc) levels. However, there is a lack of consensus regarding the efficacy of these equations in assessing eGFR, particularly for elderly individuals in China. This study aimed to evaluate the applicability of the MDRD, MDRDc, CKD-EPI series, BIS1, and FAS equations within the Chinese elderly population. Methods A cohort of 298 elderly patients with measured GFR (mGFR) was enrolled. The patients were categorized into three subgroups based on their mGFR levels. The eGFR performance was examined, taking into account bias, interquartile range (IQR), accuracy P30, and root-mean-square error (RMSE). Bland–Altman plots were employed to verify the validity of eGFR. Results The participants had a median age of 71 years, with 167 (56.0%) being male. Overall, no significant differences in bias were observed among the seven equations ( P > 0.05). In terms of IQR, P30, and RMSE, the BIS1 equation demonstrated superior accuracy (14.61, 72.1%, and 13.53, respectively). When mGFR < 30 ml/min/1.73 m 2 , all equations underestimated the true GFR, with the highest accuracy reaching only 59%. Bland–Altman plots indicated that the BIS1 equation exhibited the highest accuracy, featuring a 95% confidence interval (CI) width of 52.37. Conclusions This study suggested that the BIS1 equation stands out as the most applicable for estimating GFR in Chinese elderly patients with normal renal function or only moderate decline. 2020NL-085-03, 2020.08.10, retrospectively registered.
Skeletal muscle index (SMI), as an effective indicator of nutritional status, plays an important role in the prognosis of malignancy. However, the impact of skeletal muscle changes on tumor prognosis has not been systematically elaborated. We aimed to explore the value of skeletal muscle changes in the prognosis of distal cholangiocarcinoma (DCC) patients undergone pancreaticoduodenectomy (PD). Patients who underwent PD for DCC between 2015 and 2023 were included in this study. Demographic, laboratory and follow-up information was obtained. The cross-sectional images of skeletal muscle area at the level of the third lumbar spine was obtained based on computed tomography (CT), and the SMI was calculated by skeletal muscle mass through height squared normalization. Skeletal muscle index and skeletal muscle loss (SML) were obtained before PD and three to six months after surgery. Patients were classified into two groups (High-SML and Low-SML) based on the optimal SML cut-off value. The univariate and multivariate Cox proportional hazards analysis was conducted to evaluate the influence of SML in predicting over survival (OS) and recurrence free survival (RFS) of DCC. Of the 112 patients with distal cholangiocarcinoma, 55 (49%) were diagnosed with low SMI preoperatively. The best cut-off values of SML were − 4.01% and − 5.99% for OS and RFS. In multivariate analysis, tumor size > 2.0 cm (hazard ratio (HR) = 1.90, P = 0.017), poor differentiation (hazard ratio (HR) = 2.80, P > 0.001), higher SML (SML ≤ − 4.01%) (hazard ratio (HR) = 3.60, P < 0.001), lymph metastasis (hazard ratio (HR) = 4.00, P < 0.001) and vascular invasion (hazard ratio (HR) = 2.10, P = 0.013) were independent risk factors forOS. Meanwhile, poor differentiation (hazard ratio (HR) = 1.90, P = 0.043), higher SML (SML ≤ -5.99%) (hazard ratio (HR) = 3.80, P < 0.001) and lymph metastasis (hazard ratio (HR) = 2.60, P = 0.003) was an independent risk factor forRFS. The models combining SML and clinical characteristics had excellent predictive performance for OS and RFS. The nutritional status marker SML are effective and convenient indicators for predicting the long-term prognosis of DCC after PD, and the SMLafter PD is notable. The combination of CT quantified SML and clinical features can help clinicians predict the long-term survival of DCC patients after PD.
Peritoneal fibrosis (PF) is a common complication of long-term peritoneal dialysis (PD). It is considered as the main reason for dialysis inadequacy and PD withdrawal. Transforming growth factor beta (TGF-β) regulates the expression of stromal cell-derived factor 1 (SDF-1α) and its receptor C-X-C chemokine receptor type 4 (CXCR4) on human peritoneal mesothelial cells (HPMCs), resulting in an increased migratory potential of HPMCs and extracellular matrix (ECM) deposition in the scar tissue and eventually fibrosis. Because SDF-1α/CXCR4 activation has a vital role in the pathogenesis of PF, codelivery of a CXCR4-receptor targeting agent with an antifibrotic agent in a single nanocarrier can be a promising strategy for treating PF. Here, for the first time, AMD3100 (AMD), a CXCR4-receptor antagonist, was coformulated with sulfotanshinone IIA sodium (STS IIA) into a liposome (STS-AMD-Lips) to develop a CXCR4 receptor targeting form of combination therapy for PF. CXCR4 targeting increased the ability of liposomes to target fibrotic peritoneal mesothelial cells overexpressing CXCR4 and facilitated the ability of STS IIA treatment at the fibrotic site. The liposome had an average diameter of 103 nm with encapsulated efficiencies of above 50%. The in vivo studies confirmed the reversal of PD solution-induced epithelial-to-mesenchymal transition by STS-AMD-Lips in HPMCs. The in vivo studies also revealed the precise biodistribution of the liposomes to peritoneum. Significant reduction of the morphological lesions and decreased level of ECM proteins were observed in rats treated with STS-AMD-Lips, proving that the liposomal nanocarrier has excellent ability to reverse PF. It has been concluded that the STS-AMD-Lips exhibit specific peritoneal targeting ability and could be used to improve STS-AMD combination delivery for the treatment of PF.
Connexin hemichannels regulate many cell functions. However, the molecular mechanisms involved remain elusive. Given that hemichannel opening causes loss of ATP, we therefore speculated a potential implication of AMPK in the biological actions of hemichannels. Activation of hemichannels by removing extracellular Ca2+ led to an efflux of ATP and a weak activation of AMPK. Unexpectedly, dysfunction of hemichannels markedly potentiated AMPK activation, which was reproduced by promotion of extracellular ATP degradation or inhibition of P2 purinoceptors, but counteracted by exogenous ATP. Further analysis revealed that ATP induced a purinoceptor-dependent activation of Akt and mTOR. Suppression of Akt or mTOR augmented AMPK activation, whereas activation of Akt by transfection of cells with myr-Akt, a constitutively active form of Akt, abolished AMPK activation. In a pathological model of hemichannel opening triggered by cadmium, disclosure of hemichannels similarly enhanced AMPK activity, which protected cells from cadmium-induced cell injury through suppression of mTOR. Collectively, we unraveled a channel-mediated regulation of AMPK through purinergic signaling pathway. Furthermore, we defined AMPK as a pivotal molecule underlying the regulatory effects of hemichannels on cell survival.
The epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) is a crucial event in the induction of peritoneal fibrosis (PF), in which canonical Wnt/β-catenin signaling participates. Smads signaling is reported to interact with β-catenin and synergistically regulates EMT. This study was aimed to reveal the effect of Astragalus on β-catenin in EMT of PMCs.To obtain the role of β-catenin in EMT, gene transfer into HMrSV5 cell line and rats has been achieved. After Astragalus treatment, EMT markers and signaling pathway-related indicators were detected by western blotting, immunofluorescence, immunohistochemistry, immunoprecipitation and real time-PCR.β-catenin knockdown suppressed EMT of HMrSV5 cells. Astragalus alleviated EMT of PMCs characterized by increased E-cadherin and decreased α-SMA and Vimentin. In rat model of peritoneal dialysis (PD), Astragalus attenuated peritoneal thickening and fibrosis. Astragalus down-regulated β-catenin by stabilizing the Glycogen synthase kinase-3β (GSK-3β)/β-catenin complex and further inhibited the nuclear translocation of β-catenin. Meanwhile, Astragalus down-regulated β-catenin by enhancing Smad7 expression. Silencing Smad7 antagonized the EMT-inhibitory effect of Astragalus.Astragalus inhibits EMT of PMCs by down-regulating β-catenin. The modulation of β-catenin in peritoneum can be a novel tool to prevent PF.
To evaluate the clinical efficacy and safety of treatment of chronic primary glomerulopathy (CPG) patients of Shen deficiency and dampness heat syndrome (SDDHS) by Yishen Qingli Granule (YQG) combined with low-dose Tripterygium Wilfordii multiglycoside Tablet (TWT).Totally 231 CPG patients of SDDHS were enrolled in this study (including 60 patients from First Affiliated Hospital of Nanjing University of Chinese Medicine, 58 from First Affiliated Hospital of Nanjing Medical University, 46 from Xinqiao Hospital of Third Military Medical University, 35 from First Affiliated Hospital of Guangzhou University of Chinese Medicine, 14 from First Affiliated Hospital of Soochow University, and 18 from Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine). They were randomly assigned to the control group (116 cases) and the trial group (115 cases) according to block group method. There were 217 cases in the safety analysis set (109 cases in the trial group vs 108 cases in the control group), and 203 cases in the full analysis set (99 cases in the trial group vs 104 cases in the control group). All patients received basic treatment such as ACEI/ARB. Furthermore, YQG (consisting of raw astragalus 10 g, prepared Polygonum Multiflorum 10 g, Pyrrosia 10 g, 1.5 g each package, containing 10 g of crude drugs) was additionally given to patients in the trial group, each package, twice daily. The TWT (10 mg) was given, twice a day. The TWT dose was adjusted according to 24 h urinary total protein (UTP). The placebos of YQG and TWT were administered to those in the control group. The treatment course consisted of 24 weeks and the follow-up visit lasted for 24 weeks. The biochemical indices were observed before and after treatment including 24 h UTP, urine red cell count (U(RBC)), renal functions (BUN, SCr), blood routine test (WBC), and liver functions (SGPT, SGOT). Reverse reactions such as gastrointestinal discomfort, skin rash, and irregular menstruation were also observed.Compared with the control group, the total effective rate was better in the trial group (82.83% vs 61.54%, P < 0.01). Results of stratified comparison of UTP showed better efficacy in the trial group (0.8-3.0 g/24 h, P < 0.01). The UTP decline occurred in the trial group after 8 weeks of treatment, with stable action, showing statistical difference when compared with the control group (P < 0.01). In the trial group, U(RBC) level decreased after treatment but changed more significantly. But there was no statistical difference in the changes when compared with the control group (P > 0.05). After treatment, there were no statistical difference in safety indicators such as WBC, SGPT, and SGOT between the two groups after treatment (P > 0.05).On the basis of basic treatment such as ACEI/ARB, application of YQG combined with low-dose TWT had better effect in controlling proteinuria of CPG patients, and could help stabilizing their conditions with less adverse reactions.
In this study, we used four drying methods (hot air, freezing, infrared, and radio frequency) to dry fresh jujube and its polysaccharide extracts by a two-step drying method, and the effects of the drying methods on the physical and chemical properties, structural properties, and antioxidant activity of jujube polysaccharides were studied. The results showed significant differences in the yield, drying time, monosaccharide content, molecular weight, apparent viscosity, thermal stability, and microstructure of the polysaccharides treated under the different drying methods. In contrast, no significant differences in the monosaccharide composition and functional groups of the polysaccharide samples obtained from the different drying methods were observed. Among all the tested methods, the freeze-drying extraction rate was the highest, reaching 4.52 ± 0.19%, while its drying time was the longest. Although the extraction rate of radio frequency drying was only 3.55 ± 0.21%, the drying time was the shortest, compared with hot air drying, the drying time was reduced by 76.67–83.29%, and the obtained polysaccharides exerted good antioxidant activity. Therefore, radio frequency drying is a potential polysaccharide extraction and drying technique, and this study can provide a theoretical basis for its industrial production.
Thioredoxin (Trx) is a small redox protein that underlies aggressive tumor growth and resistance to chemotherapy. Inhibition of Trx with the chemical inhibitor PX-12 suppresses tumor growth and induces cell apoptosis. Currently, the mechanism underlying the therapeutic actions of PX-12 and the molecules influencing cell susceptibility to PX-12 are incompletely understood. Given that connexin43 (Cx43), a tumor suppressor, regulates tumor cell susceptibility to chemotherapy, we examined the possible involvement of Cx43 in PX-12-induced cell death. Exposure of cells to PX-12 led to a loss of cell viability, which was associated with the activation of oxidative sensitive c-Jun N-terminal kinase (JNK). Inhibition of JNK or supplement of cells with anti-oxidants prevented the cell-killing action of PX-12. The forced expression of Cx43 in normal and tumor cells increased cell sensitivity to PX-12-induced JNK activation and cell death. In contrast, the downregulation of Cx43 with siRNA or the suppression of gap junctions with chemical inhibitors attenuated JNK activation and enhanced cell resistance to PX-12. Further analysis revealed that PX-12 at low concentrations induced a JNK-dependent elevation in the Cx43 protein, which was also preventable by supplementing the cells with anti-oxidants. Our results thus indicate that Cx43 is a determinant in the regulation of cell susceptibility to PX-12 and that the upregulation of Cx43 may be an additional mechanism by which PX-12 exerts its anti-tumor actions.
Abstract China is the largest producer of jujubes in the world, with the Xinjiang region accounting for about 50 % of the total production. However, local jujube processing still relies on traditional methods, leading to reduced industrial efficiency. Research shows that jujube polysaccharides possess various biological properties, such as antioxidant, anti-tumor, and anti-inflammatory activities. Enhancing the extraction of jujube polysaccharides to boost their food, medicinal, and economic value has become an important development direction of the jujube industry. This paper reviews the current research on the active functions of grey jujube polysaccharides, extraction technologies, and recent advancements in their production and application. It systematically introduces both traditional and emerging extraction technologies and summarizes the current state of production and application of grey jujube polysaccharides. The aim is to provide references for other researchers interested in jujube polysaccharides and to extend the value chain of the grey jujube industry.
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