0.05).Conclusion:Ionizing radiation-induced color change combined with chrominance technique may provide a new convenient method for studying radiation absorbed dose.

Objective To find the similarities and differences between SD rat and C 57 mouse models of chronic renal failure established by 5/6 nephrectomy ,and select an appropriate experimental animal for the study of the treatment and prevention of chronic renal failure .Methods 60 SD rats and C57 mice were randomly and equally divided into 5/6 nephrectomy group and sham operatied group .The mice and rats were killed at 4 weeks , 8 weeks and 12 weeks after the operation, respectively.Serum and renal tissue samples were collected for the detection and analysis of renal function andα-SMA.Results There was no significant difference in the survival rates between the rat and mouse models (P>0.05). The serum creatinine and urea nitrogen in the 5/6NX rat group showed a stable state at 8-12 weeks, which was different from that of the 5/6NX mouse group.Conclusions A 5/6 nephrectomy mouse model of chronic renal failure is successfully established .Although both 5/6 NX mouse and rat groups appear progressive renal failure after the operation , their disease processes are not quite the same .In clinic, appropriate experimental animals should be selected according to the length of the observation period in order to accurately show the disease states .

Objective To investigate the change of Na+ /dicarboxylate cotransporter (SDCT) 1 expression in renal tissues of rats with nephrolithiasis induced by ethylene glycol (EG) and the mechanism of potassium citrate prevention. Methods Male Wistar rats were divided into control, nephrolithiasis and potassium citrate treated groups. Calcium oxalate crystal deposition and histological changes in kidney were examined by anatomical and light microscope. The plasma and urinary biochemical parameters, such as citrate, oxalate etc., were analyzed by routine biochemical method. The expression of SDCT1 mRNA in kidneys was determined by Northern blot, and the change of SDCT1 protein abundance was detected by immunohistochemistry. Results On day 3, the animals in the nephrolithiasis group had a higher level of SDCT1 mRNA and protein abundance in kidneys, as well as a lower level of citrate in the urine when compared with the control group. However none of the rats in this group had obviously calcium oxalate crystal deposition in kidneys. On day 7 and 14, the expression of SDCT1 mRNA and protein abundance were shown further increase, when the urinary citrate concentration was decreased progressively, and 87. 5% to 100% of the rats in this group displayed a large quantity of calcium crystal deposition in the kidney. In the potassium citrate treated group, both the expression of SDCT1 mRNA and protein abundance were shown almost complete inhibited during the whole experiment time, meanwhile the urinary citrate level was significantly elevated with time; furthermore, the occurrence of the renal crystal deposition decreased to 37. 5% on day 14, and the pathologic changes such as tubular dilation and inflammatory cells infiltration were shown to be alleviated. Conclusions The upregulation of SDCT1 mRNA and protein abundance in kidney has a close relationship with hypocitraturia, which may play an important role in the development of nephroliathisis. The treatment with potassium citrate has a beneficial effect on the experimental nephrolithiasis rats through inhibiting the expression of SDCT1 in the renal tissue.

ObjectⅣe To investigate the effect of sense and antisense TIMP-1 on the expression of FN and type Ⅳ collagen of rat glomerular mesangial cells in vitro. Methods Two recombinant retroviral vectors, pLXIN-TIMP-1 (PLT)encoding sense TIMP-1 and pLXIN-ATIMP-1 (PLA)encoding antisense TIMP-1 were constructed by using DNA recombining techniques. These two vectors were then introduced into the PA317 packaging cell line with lipofectin DOTAP. The high-titer retroviral supematants containing sense or antisense TIMP-1 were used to infect rat glomerular mesangial cells. PCR and Northern blot were used to detect the integration and expression of human TIMP-1. Northern blot and ELISA were employed to investigate the expression of endogenous TIMP-1, FN, and Ⅳ collagen. Results Both sense and antisense TIMP-1 were successfully integrated into rat mesangial cells and expressed the sense and antisense ITMP-1 RNA. Overexpression of TIMP-1 induced by sense TIMP-1 caused upregulation of FN and Ⅳ type collagen in protein level, in contrast, supprssion of TIMP-1 expression by antisense TIMP-1 caused downregulation of FN and Ⅳ type collagen protein; but neither sense nor antisense TIMP-1 infection had effects on the RNA level of FN and Ⅳ type collagen. Conclusion TIMP-1 suppresses the degradation of ECM in rat glomerular mesangial cells and antisense TIMP-1 may be available for renal fibrosis in the future.

Objective To evaluate the prevalence and risk factors of progressive liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD).Methods A total of 2 054 subjects who underwent health check up and were diagnosed as NAFLD in 9 institutions were included in the study.Blood routine and biochemical findings were collected to calculate aspartate aminotransferase-to-platelet ratio index (APRI).Subjects were divided into three groups according to diagnostic threshold of liver fibrosis:APRI ＜0.43 group,APRI 0.43-0.53 group and APRI ≥ 0.54 group.The correlation between APRI and biochemical variables was analyzed,and the risk factors of progressive fibrosis were also analyzed.Results Among 2 054 subjects (male/female 1 598/456) there were 61 cases with APRI ≥ 0.98 (2.97％,progressive fibrosis),318 with APRI ≥0.54 (15.48％),1 475 with APRI ＜ 0.43 (71.81％),261 with APRI 0.43-0.53 (12.71％).Logistic stepwise regression analysis showed that TG (P =0.002,OR =1.095,95％CI:1.033-1.161),2 hPG(P =0.000,OR =1.103,95％ CI:1.058-1.151,BUN(P =0.034,OR =1.215,95 ％ CI:1.014-1.454) were risk factors,and H DL-C (P =0.034,OR =0.353,95 ％ CI:O.135-0.924) was a protective factor for the progression of fibrosis.Conclusion The progressive fibrosis in patients with NAFLD is closely associated to blood glucose and lipid metabolism disorder.

OBJECTIVE:To evaluate therapeutic efficacy and safety of Aidi injection combined with S-1 for advanced gastric cancer systematically,and to provide evidence-based reference. METHODS:Retrieved from CJFD,Wanfang database,VIP, CBM,Cochrane Library,PubMed and EMBase,randomized controlled trials(RCTs)about Aidi injection combined with S-1(tri-al group) vs. S-1 alone (control group) for advanced gastric cancer were collected. Meta-analysis was conducted by Rev Man 5.3 software after data extraction and quality evaluation by risk bias evaluation tool of Cochrane Handbook Version 5.1.0. RESULTS:A total of 8 RCT were included,involving 690 patients. Results of Meta-analysis showed that there was no statistical significance in therapeutic efficacy of solid tumor between 2 groups [OR=1.19,95%CI(0.88,1.61),P=0.26]. The improvement rate of survival quality[OR=3.62,95%CI(2.48,5.30),P<0.001],immunoglobulin level [CD3:SMD=1.31,95%CI(1.06,1.56),P<0.001;CD4:SMD=1.71,95%CI(1.38,2.04),P<0.001;CD8:SMD=-1.46,95%CI(-1.68,-1.23),P<0.001;CD4/CD8:SMD=1.45,95%CI(1.14,1.76),P<0.001] in trial group was significantly higher than control group. The incidence of leukopenia [RR=0.52,95%CI (0.40,0.68),P<0.001],thrombocytopenia [RR=0.49,95%CI(0.36,0.67),P<0.001] and gastrointestinal disorder [RR=0.56,95%CI(0.43,0.71),P<0.001] in trial group were significantly lower than control group,with statistical significance. CONCLUSIONS:Compared to S-1 alone,S-1 combined with Aidi injection can not significantly improve therapeutic efficacy of solid tumor therapy, but can improve survival quality and immunity of patients,as well as reduce the occurrence of ADR.

Background: The emergence of the severe acute respiratory syndrome coronavirus 2 omicron variant has been triggering the new wave of coronavirus disease 2019 (COVID-19) globally. However, the risk factors and outcomes for radiological abnormalities in the early convalescent stage (1 month after diagnosis) of omicron infected patients are still unknown. Methods: Patients were retrospectively enrolled if they were admitted to the hospital due to COVID-19. The chest computed tomography (CT) images and clinical data obtained at baseline (at the time of the first CT image that showed abnormalities after diagnosis) and 1 month after diagnosis were longitudinally analyzed. Uni-/multi-variable logistic regression tests were performed to explore independent risk factors for radiological abnormalities at baseline and residual pulmonary abnormalities after 1 month. Results: We assessed 316 COVID-19 patients, including 47% with radiological abnormalities at baseline and 23% with residual pulmonary abnormalities at 1-month follow-up. In a multivariate regression analysis, age ≥ 50 years, body mass index ≥ 23.87, days after vaccination ≥ 81 days, lymphocyte count ≤ 1.21 × 10 -9 /L, interleukin-6 (IL-6) ≥ 10.05 pg/mL and IgG ≤ 14.140 S/CO were independent risk factors for CT abnormalities at baseline. The age ≥ 47 years, presence of interlobular septal thickening and IL-6 ≥ 5.85 pg/mL were the independent risk factors for residual pulmonary abnormalities at 1-month follow-up. For residual abnormalities group, the patients with less consolidations and more parenchymal bands at baseline could progress on CT score after 1 month. There were no significant changes in the number of involved lung lobes and total CT score during the early convalescent stage. Conclusion The higher IL-6 level was a common independent risk factor for CT abnormalities at baseline and residual pulmonary abnormalities at 1-month follow-up. There were no obvious radiographic changes during the early convalescent stage in patients with residual pulmonary abnormalities.

Objective:To investigate the effect of Stigma Maydis Palysaccharide(SMPS)on ATP synthesis in kidney mitochondria of D-galactose-induced aging mice, and to clarify its possible mechanism.Methods:The aging mouse model was established by subcutaneous injection of D-galactose solution in the back of the neck.The 48 SPF male mice were randomly divided into normal control group(control group), D-galactose model group(D-Gal group), SMPS low-dose group and SMPS high-dose group(n=12 for each). The control group was subcutaneously injected with 150 mg/kg normal saline on the back of the neck every day, while the other three groups were subcutaneously injected with 150 mg/kg of D-gal solution on the back of the neck every day.SMPS-L and-H dose groups were given 30 mg/kg and 60 mg/kg of SMPS solution by gavage at the same day of D-Gal injection.The control group and D-GAL group were given the same volume of normal saline daily by gavage for 42 days.Blood samples were collected from the eyeball under general anesthesia after 42 days of intervention for the detection of serum levels of superoxide dismutase(SOD), glutathione peroxidase(GSH-Px)and MDA.After harvesting the kidney tissue, various tests were used to detect ATP content, the mRNA expression levels and protein expression levels in kidney.Luciferase assay was used to detect ATP content in renal tissue.Real-time fluorescent quantitative PCR was used to detect the mRNA expression levels of succinate dehydrogenase(SDH)of complex Ⅱ, cytochrome C reductase(Cycs)of complex Ⅲ, complex Ⅳ(COXⅣ)and ATP5b in ATP synthase in mitochondrial oxidative respiratory chain.Western blot was used to detect the expression levels of mitochondrial fusion protein 2(MFN2), dynamin-related protein1(DRP1)and mitochondrial autophagy related protein P62 in renal tissues of each group.Results:Compared with control group, the activities of serum of SOD(116.53±10.01)U/mg and GSH-Px(127.58±8.74)μmol/L were significantly decreased in D-GAL group(both P< 0.01), and serum MDA content(15.42±0.91)μmol/L increased significantly in D-GAL group( P<0.01). Compared with D-GAL group, the activities of SOD(152.80±9.29)U/mg and GSH-Px(274.07±10.73)μmol/L were significantly increased in SMPS intervention group( P< 0.01), while the MDA content(8.10±0.66)μmol/L decreased significantly in SMPS intervention group( P< 0.01). Compared with control group, the content of ATP(178±4)10 -4 μmol in D-gal group was significantly decreased( P<0.01), the mRNA expression levels of SDH, Cycs and COXⅣ were not significantly changed in D-gal group, and the mRNA expression level of ATP5b(0.67±0.01)was down-regulated in D-gal group( P<0.01), the expression of MFN2 protein(0.29±0.02)was significantly decreased in D-gal group( P<0.01), and the expression of DRP1 and P62 protein(0.31±0.02 and 0.21±0.01)was significantly increased in D-gal group(both P<0.01). Compared with the D-gal group, the ATP content(193±1)10 -4 μmol in the kidney tissue of the mice was significantly increased in SMPS intervention group( P< 0.01), and the ATP5b mRNA expression and MFN2 protein expression(0.87±0.05 and 0.71±0.08)were significantly increased in SMPS intervention group(both P< 0.01), DRP1 and P62 protein expressions(0.20±0.01 and 0.10±0.01)were significantly down-regulated in in SMPS intervention group(both P< 0.01). Conclusions:SMPS can improve the mitochondrial dynamic homeostasis disorder in aging mice by increasing the activity of antioxidant enzymes, up-regulating the expression of ATP5b mRNA and MFN2 protein, down-regulating the expression of DRP1 and P62 protein, and promoting the generation of mitochondrial ATP in D-gal-induced aging mice kidney tissue.

In recent years, modeling and simulation technology based on pharmacometrics has received increasing attention in the development of innovation drugs. In August of 2021, FDA issued a guidance named Pharmacokinetic-Based Criteria for Supporting Alternative Dosing Regimens of Programmed Cell Death Receptor-1 (PD-1) or Programmed Cell Death-Ligand 1 (PD-L1) Blocking Antibodies for Treatment of Patients with Cancer Guidance for Industry, claiming the necessity of using population PK-based simulation method for the optimization of dosing regimens, and the corresponding implementation standards. This article first summarized the existing therapeutic regimens of PD-1/PD-L1 blocking antibodies in clinic as well as the main content of the guidance, and then cited some actual examples where population PK-based simulation method did contribute to the approval of the alternative dosing regimens. Besides, some critical considerations for the dosing regimen optimization of PD-1/PD-L1 blocking antibodies were also analyzed. In our view, this guidance would have positive impacts on the development of PD-1/PD-L1 blocking antibodies in the future. We hope that this article may provide some references for the colleagues in China.

Background: Xylazole (Xyl) is a veterinary anesthetic that is structurally and functionally similar to xylazine. However, the effects of Xyl in vitro remain unknown. Objectives: This study aimed to investigate the anesthetic mechanism of Xyl using fetal rat nerve cells treated with Xyl. Methods: Fetal rat nerve cells cultured for seven days were treated with 10, 20, 30, and 40 μg/ mL Xyl for 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, and 120 min. Variations of amino acid neurotransmitters (AANTs), Nitric oxide-Cyclic GMP (NO-cGMP) signaling pathway, and ATPase were evaluated. Results: Xyl decreased the levels of cGMP and NO in nerve cells. Furthermore, Xyl affected the AANT content and Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase activity in nerve cells. These findings suggested that Xyl inhibited the NO-cGMP signaling pathway in nerve cells in vitro. Conclusions This study provided new evidence that the anesthetic and analgesic effects of Xyl are related to the inhibition of the NO-cGMP signaling pathway.