OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.

AIM: To explore the effects of preoperative anterior segment parameters on the rotational stability of Toric intraocular lens(Toric IOL).METHODS:Prospective study. A total of 41 cataract patients(54 eyes)with combined corneal regular astigmatism from March to December 2023 were included and treated with cataract phacoemulsification combined with plate loop Toric IOL implantation in the Department of Ophthalmology of the First Affiliated Hospital of Zhengzhou University. The rotation degree of Toric IOL and uncorrected distance visual acuity(UCDVA)were evaluated at 1 d, 2 wk, and 1 mo postoperatively, the corrected distance visual acuity(CDVA)was evaluated at 2 wk and 1 mo after surgery, and the decentration and tilt of the Toric IOL were assessed at 2 wk postoperatively.RESULTS:A total of 33 patients(40 eyes)were included in this study. The UCDVA(LogMAR)of 1 d, 2 wk and 1 mo postoperatively were 0.10(0.10, 0.30), 0.05(0, 0.10)and 0(0, 0.10), respectively, which was improved compared with the preoperative levels of [0.80(0.49, 1.00)](P<0.001). The CDVA(LogMAR)of 2 wk and 1 mo postoperatively were 0.05(0, 0.15)and 0(0, 0.138), respectively, which was improved compared with preoperative levels of [0.52(0.40, 0.80)](P<0.001). The residual astigmatism of 2 wk and 1 mo postoperatively were 0.625(0.25, 0.75)D and 0.50(0.25, 0.75)D, respectively, which was significantly reduced compared with preoperative astigmatism of [1.82(1.31, 2.59)D](P<0.001). The preoperative anterior segment length(ASL), and lens thickness(LT)were positively correlated with Toric IOL rotation degree at 1 d(rs=0.463, P=0.003; rs=0.340, P=0.032)and 2 wk(rs=0.520, P=0.001; rs=0.409, P=0.009)postoperatively. At 1 mo postoperatively, only ASL was positively correlated with Toric IOL rotation degree(rs=0.463, P=0.003). The results of linear regression analysis showed that preoperative ASL was a predictor of rotation degree at 1 d, 2 wk and 1 mo after surgery(F1 d=10.098, P1 d=0.003; F2 wk=16.915, P2 wk<0.001; F1 mo=10.957, P1 mo=0.002). The rotation degree of Toric IOL was positively correlated with lens decentration(rs=0.360, P=0.043).CONCLUSION:The early postoperative rotation of Toric IOL is positively correlated with ASL, and the rotation is also positively correlated with lens decentration.

OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

Objective To analyze the correlation between cumulative fluid balance volume and increasing plasma volume and aggravated clinical congestion symptoms in patients with heart failure on admission for 1～7 d,and to explore the application value of cumulative fluid balance volume in predicting volume overload.Methods Using the convenience sampling method,235 heart failure patients hospitalized from October 2022 to February 2023 in a total of 3 tertiary hospitals in Nanjing,Lianyungang,Jiangsu Province,and Zhumadian,Henan Province,were selected and classified into an increasing/decreasing plasma volume group and an aggravated/alleviated clinical congestion symptoms group.General information,clinical characteristics,and 1～7 d cumulative fluid balance volume of the study subjects were collected to compare the differences in cumulative fluid balance volume between the 2 groups.Logistic regression was used to analyze the effect of cumulative fluid balance volume on plasma volume and clinical congestion symptoms.Receiver operating characteristic curves were used to analyze the optimal cutoff value of cumulative fluid balance volume for predicting increasing plasma volume and aggravated clinical congestion symptoms.Results Excluding 15 pat ients who were discharged early and 3 patients with inaccurate records of fluid intake and excretion,a total of 217 patients were included.The incidence of positive fluid balance was lowest on day 1,at 65.90%,with the smallest cumulative volume of(0.235±0.983)L;the highest incidence of positive balance occurred on day 6,at 75.58%,with the largest cumulative volume of(2.444±5.445)L.The cumulative fluid balance at 4～7 d in the increasing plasma volume group was higher than that in the decreasing plasma volume group,and the difference was statistically significant(P<0.05);the cumulative fluid balance at 4～7 d was an independent risk factor for plasma volume elevation,and a cumulative fluid balance of 2.308,3.361,3.518,and 3.702 L at 4～7 d was predictive of a plasma volume elevation,and areas under receiver operating characteristic curve were 0.686,0.721,0.647,and 0.766,respectively.The cumulative fluid balance for 4～7 d in the aggravated clinical congestion symptoms group was higher than that in the alleviated clinical congestion symptoms group,and the difference was statistically significant(P<0.05);the cumulative fluid balance for 4～7 d was an independent risk factor for the aggravated clinical congestion symptoms,and a cumulative fluid balance for 4～7 d of 2.574,3.383,4.995,and 4.235 L predicted aggravated clinical congestion symptoms,and area under receiver operating characteristic curve was 0.640,0.693,0.654,and 0.720,respectively.Conclusion The incidence of cumulative positive fluid balance in heart failure patients is high,and the amount of cumulative fluid balance can better predict the occurrence of volume overload,and the increase of plasma volume precedes the appearance of clinical congestion symptoms.It is suggested that heart failure patients with more than 3 d of cumulative positive balance should be closely monitored,and when the cumulative positive balance exceeds 2.308 L,measures should be taken in time to drain excessive fluid,so as to avoid the incidence of volume overload.

Objective To explore the differences in brain functions between individuals with good acclimatization to high altitudes and those with poor acclimatization based on microstate and functional connectivity analysis of resting-state electroencephalogram(EEG)activities.Methods A total of 44 residents exposed to the high-altitude environment of 3 650 m above sea level were enrolled.They were divided into two groups according to their findings for the high-altitude acclimatization index(AAI),with 22 in the good acclimatization group and 22 in the poor acclimatization group.The good acclimatization group had 10 males and 12 females of the mean age of(20.48±2.09)years.Among them,10 were Tibetans,and 12 were Han Chinese.The poor acclimatization group consisted of 18 males and 4 females,with a mean age of(18.90±1.25)years.Among them,7 were Tibetans,and 15 were Han Chinese.The K-means clustering algorithm was used to classify EEG microstates into four categories of A,B,C,and D.The average duration,coverage,occurrence frequency,and transition probabilities between microstates were compared.Coherence analysis(COH)was performed to assess the strength of brain network connectivity.Results Compared to the good acclimatization group,the poor acclimatization group exhibited a longer duration,higher occurrence frequency,and coverage of microstate C.The coverage of microstate D was also higher,while the occurrence frequency and coverage of microstate B were lower.The poor acclimatization group showed a decrease in transitions from microstate B to A or D,while transitions from C to B or D,and those from D to A or C increased,showing statistically significant differences between the groups(P＜0.05).In the α,β,δ,and θ frequency bands,the poor acclimatization group had higher COH strength in regions such as the frontal and occipital lobes,showing symmetrical functional connectivity between the left and right hemispheres.Conclusion The good and poor high-altitude acclimatization groups exhibit different neural mechanisms in terms of microstates and functional connectivity.There are significant differences between individuals with good acclimatization and those with poor acclimatization regarding visual information processing,interference resistance,brain network stability,and coherence.

Humans ; HIV-1/genetics* ; Anti-Retroviral Agents/therapeutic use* ; Mutation/genetics* ; Treatment Failure ; HIV Infections/genetics* ; Drug Resistance, Viral/genetics* ; Anti-HIV Agents/therapeutic use* ; Genotype

In this study, a single base editing system was used to edit the FecB and GDF9 gene to achieve a targeted site mutation from A to G and from C to T in Ouler Tibetan sheep fibroblasts, and to test its editing efficiency. Firstly, we designed and synthesized sgRNA sequences targeting FecB and GDF9 genes of Ouler Tibetan sheep, followed by connection to epi-ABEmax and epi-BE4max plasmids to construct vectors and electrotransfer into Ouler Tibetan sheep fibroblasts. Finally, Sanger sequencing was performed to identify the target point mutation of FecB and GDF9 genes positive cells. T-A cloning was used to estimate the editing efficiency of the single base editing system. We obtained gRNA targeting FecB and GDF9 genes and constructed the vector aiming at mutating single base of FecB and GDF9 genes in Ouler Tibetan sheep. The editing efficiency for the target site of FecB gene was 39.13%, whereas the editing efficiency for the target sites (G260, G721 and G1184) of GDF9 gene were 10.52%, 26.67% and 8.00%, respectively. Achieving single base mutation in FecB and GDF9 genes may facilitate improving the reproduction traits of Ouler Tibetan sheep with multifetal lambs.
Animals ; Sheep/genetics* ; Gene Editing ; Tibet ; Mutation ; Phenotype ; Mutagenesis, Site-Directed

Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.

Male ; Humans ; Aged ; Sleep Duration ; Aging ; Testosterone ; China ; Sleep