Fuchs endothelial corneal dystrophy(FECD)is a progressive dystrophic disease characterized by gradual damage to the corneal endothelium, ultimately leading to endothelial decompensation. The current standard treatment, corneal transplantation, has several limitations. Recent studies have shown that Rho-associated kinase(ROCK)inhibitors can promote cell proliferation by modulating the cyclin D and p27 signaling pathways. Additionally, ROCK inhibitors activate Rac1, which drives the actin-related protein complex(ARPC2)to enhance cell adhesion, and regulate processes such as membrane blebbing, nuclear disintegration, and apoptotic body formation, thereby inhibiting the apoptosis of corneal endothelial cells. These findings suggest that ROCK inhibitors may be a promising therapeutic approach for FECD. This review provides an overview of the pharmacological effects, basic research, clinical trials, and potential adverse reactions associated with ROCK inhibitors in the treatment of FECD, with the aim of developing compounds with stable efficacy and minimal side effects for the treatment of FECD in the near future.

BACKGROUND: Peripheral helper T (T PH ) cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production. However, the phenotype, function, and clinical relevance of T PH cells in hepatocellular carcinoma (HCC) are currently unknown. METHODS: Blood, tumor, and peritumoral liver tissue samples from 39 HCC patients (Sep 2016-Aug 2017) and 101 HCC patients (Sep 2011-Dec 2012) at the Third Affiliated Hospital of Sun Yat-sen University were used. Flow cytometry was used to quantify the expression, phenotype, and function of T PH cells. Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC. T PH cells, CD19 + B cells, and T follicular helper (T FH ) cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays. RESULTS: T PH cells highly infiltrated tumor tissues, which was correlated with tumor size, early recurrence, and shorter survival time. The tumor-infiltrated T PH cells showed a unique ICOS hi CXCL13 + IL-21 - MAF + BCL-6 - phenotype and triggered naïve B-cell differentiation into regulatory B cells. Triggering programmed cell death protein 1 (PD-1) induced the production of C-X-C motif chemokine ligand 13 (CXCL13) by T PH cells, which then suppressed tumor-specific immunity and promoted disease progression. CONCLUSION Our study reveals a novel regulatory mechanism of T PH cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T PH cells and that of antitumorigenic T FH cells in the HCC microenvironment.
Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Humans ; T-Lymphocytes, Helper-Inducer/metabolism* ; Animals ; Mice ; Male ; Female ; Mice, Inbred C57BL ; Middle Aged ; B-Lymphocytes, Regulatory/metabolism* ; Flow Cytometry ; Interleukin-21 ; Aged ; Chemokine CXCL13/metabolism*

BACKGROUND:Abnormal extracellular matrix accumulation and excessive proliferation of fibroblasts are the main manifestations of pathological scars.Excessive proliferation of fibroblasts leads to the production of large amounts of collagen-based extracellular matrix.Therefore,to investigate the role of fibroblast fibrosis in the formation of pathological scar will provide a new idea for revealing the mechanism of pathological scar and biological therapy. OBJECTIVE:To investigate the effect of RAS-selective lethal small molecule 3(RSL3)on the fibrosis of human pathological scar fibroblasts. METHODS:Then cases of pathological scar tissue and normal skin tissue samples from the same individuals,provided by the Department of Burn Plastic Surgery,General Hospital of Ningxia Medical University,were collected.Fibroblasts of human pathological scar and human normal skin were extracted and used in the following experiments.The general condition of the pathological scar tissue and the normal skin tissue was detected by hematoxylin-eosin staining.The appearance of fibroblasts from pathological scar and normal skin were observed by inverted microscope.The fibroblasts were verified by immunofluorescence assay.The cells were treated with different concentrations of RSL3(1,3,5,7,9,11,13 μmol/L).The inhibitory concentration of RSL3 on fibroblasts was detected by cell counting kit-8.Control group(without treatment)and RSL3 intervention group(treated with 7 μmol/L RSL3 for 24 hours)were set up.The mRNA and protein expressions of glutathione peroxidase 4,type Ⅰ collagen,type Ⅲ collagen and α-smooth muscle actin were detected by Qrt-PCR and western blot,respectively.Level of malondialdehyde in cells was detected.The residual scratch area was measured by cell scratch test after 24 hours to calculate the percentage of residual scratch area. RESULTS AND CONCLUSION:The expression of glutathione peroxidase 4 in the pathological scar group was higher than that in the normal skin group(Mrna:t=3.252,P<0.01;protein:t=5.075,P<0.01).The expression of glutathione peroxidase 4 in the pathological scar fibroblast group was higher than that in the normal skin fibroblast group(Mrna:t=10.32,P<0.01;protein:t=26.22,P<0.01).Compared with the control group,the expression of glutathione peroxidase 4 was decreased(Mrna:t=2.798,P<0.05;protein:t=4.643,P<0.01),the content of malondialdehyde was increased(t=2.917,P<0.05),the expression of type Ⅰ collagen(Mrna:t=15.84,P<0.01;protein:t=4.610,P<0.01),type Ⅲ collagen(Mrna:t=28.86,P<0.01;protein:t=7.713,P<0.01)and α-smooth muscle actin(Mrna:t=2.671,P<0.05;protein:t=7.417,P<0.01)were decreased in the RSL3 intervention group.Compared with the control group,the migration ability was weakened in the RSL3 intervention group(t=14.06,P<0.01).To conclude,RSL3 can inhibit the expression of glutathione peroxidase 4 and then inhibit the ability of fibrosis and migration of pathological scar fibroblasts.

Eclipta prostrata L.has been used in traditional medicine and known for its liver-protective properties for centuries.Wedelolactone(WEL)and demethylwedelolactone(DWEL)are the major coumarins found in E.prostrata L.However,the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease(NAFLD)still remains to be explored.Utilizing a well-established zebrafish model of thioacetamide(TAA)-induced liver injury,the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis.Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver.The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped,and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized.Based on spatial metabolomics and transcriptomics,we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL.Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD,and presents a"multi-omics"platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.

Objective To investigate the relationship between serum fatty acid binding protein(FABP)1,FABP2 and diabetic kidney disease(DKD)in patients with type 2 diabetes mellitus(T2DM)and its diagnostic value.Methods A total of 170 patients with T2DM diagnosed and treated in this hospital from January 2020 to December 2022 were selected as the research objects.According to urinary albumin to creatinine ratio(UACR),they were divided into non-DKD group(UACR<30 mg/g,72 cases)and DKD group(UACR≥30 mg/g,98 cases).A total of 60 healthy people in the same hospital during the same period were selected as the control group.Pearson correlation analysis was used to analyze the correlation between serum FABP1,FABP2 and renal function related indicators.Multivariate Logistic regression was used to analyze the influencing fac-tors of DKD.Receiver operating characteristic curve was used to evaluate the diagnostic efficacy of serum FABP1 and FABP2 for DKD.Results The DKD group had significantly higher serum levels of FABP1 and FABP2 than the non-DKD group and the control group(P<0.05),and the non-DKD group had significantly higher serum levels of FABP1 and FABP2 than the control group(P<0.05).Compared with the non-DKD group,the DKD group had a significantly lower eGFR and significantly higher UACR,serum creatinine,blood urea nitrogen,and serum uric acid levels(P<0.05).Serum FABP1 and FABP2 levels were positively correla-ted with UACR,serum creatinine,blood urea nitrogen,and negatively correlated with eGFR(P<0.05).In-creased serum FABP1 and FABP2 levels were independent risk factors for DKD.The serum FABP1,FABP2 joint detection diagnosis efficiency was better than that of serum FABP1,FABP2 detection alone(Z=4.712,4.363,P=0.001,0.002).Conclusion The serum levels of FABP1 and FABP2 are increased in patients with DKD,and they are related to the degree of renal function damage,which are independent risk factors for the occurrence of DKD in patients with T2DM.The combined detection of FABP1 and FABP2 has a high diagnos-tic efficiency for the occurrence of DKD in patients with T2DM.

OBJECTIVE To analyze the changes of volatile co mponents in Olibanum and its processed products ，and to determine the contents of 4 components as octyl acetate. METHODS The volatile oil of Olibanum ，fried Olibanum and Olibanum stir-baked with vinegar were extracted. The components of volatile components were identified by GC-MS. The structure identification and data analysis of the chemical components with similarity ≥80％ were performed by using Xcalibur 4.0 software and NIST 2.0 mass spectrum database. The peak area normalization method was used to calculate the relative content of each component. GC method was adopted to simultaneously determine and compare the contents of limonene ，octyl acetate ，linalool and n-octanol in volatile components of Olibanum and its processed products. RESULTS Thirteen components were identified from volatile components of Olibanum ，fried Olibanum and Olibanum stir-baked with vinegar ，mainly including alcohols ，olefins and esters；among them ，relative contents of octyl acetate in Olibanum ，fried Olibanum and Olibanum stir-baked with vinegar were higher，which were 23.86％ ，37.80％ and 53.86％ respectively. The linear ranges of limonene ，octyl acetate ，linalool and n-octanol were 0.006 6-0.066 4，0.179 2 -1.792 0，0.003 7-0.037 0 and 0.032 8-0.328 0（r＞0.999 5）respectively；RSDs of precision，repeatability and stability （24 h）tests were all less than 2％；average recoveries were 98.56％，100.02％，99.13％ and 98.66％，respectively（RSD≤2.16，n＝6）. Average contents of 4 components in Olibanum were 0.15％，16.27％，0.36％ and 2.26％，while those of fried Olibanum were 0.85％，17.58％，0.66％ and 3.47％，respectively；those of Olibanum stir-baked with vinegar were 0.50％，19.75％，0.58％ and 3.34％，respectively. Compared with Olibanum ，average contents of octyl acetate ， linalool，n-octanol and limonene in volatile components of fried Olibanum and Olibanum stir-baked with vinegar were increased significantly（P＜0.05 or P＜0.01）. Compared with fried Olibanum ，average contents of limonene ，linalool and n-octanol were decreased significantly ，while those of octyl acetate were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS After fried and stir-baked with vinegar ，the volatile components in Olibanum are similar ，but the relative contents are different ，and the contents of octyl acetate and other components are increased.

At present, the main treatment strategy for acute ischemic stroke is to recanalize the occluded blood vessels through drug or endovascular interventional therapy, and to save the ischemic penumbra is the key of the treatment, but due to the factors such as time window and indications, some patients cannot benefit from them. NeuroFlo technology can redistribute blood flow in body, increase intracranial blood supply, promote the establishment of collateral circulation around infarctions, effectively save ischemic penumbra, and ultimately improve the long-term prognosis of patients.

OBJECTIVE: To investigate the feasibility of using 8-hydroxy-2'deoxyguanosine(8-OHdG) in blood and urine samples as biomarkers for the evaluation of human DNA oxidative damage caused by diesel exhaust(DE). METHODS: A convenient sampling method was used to select 56 male workers exposed to DE in a car manufacturing factory as exposure group, and 52 male workers without exposure to DE were selected as the control group.Urine samples and blood samples were collected from workers in the 2 groups 8 hours after work, and the levels of 8-OHdG in urine and plasma were measured by ultra-high performance liquid chromatography tandem mass spectrometer. RESULTS: The median level of urinary 8-OHdG in the exposure group was higher than that of control group(2.54 vs 2.03 μg/g Cr, P<0.05). The median levels of plasma 8-OHdG in the exposure group and control group showed no statistical significance(32.20 vs 31.40 ng/L, P>0.05). CONCLUSION: The urinary 8-OHdG can be used as a biomarker for evaluating the oxidative damage induced by DE exposure.

Objective To acquire some related data of surgical approach through brain superior temporal sulcus to temporal horn of lateral ventricle by MRI volume rendering, and to orientate the point of superior temporal sulcus on the lateral surface which is closest to temporal horn of lateral ventricle,and to find out the best entrance point of surgical approach through superior temporal sulcus to temporal horn of lateral ventricle.Methods 120 adult cases of MRI scanning specimens were chosen for measurement. MRI volume rendering technology was used to rebuild the brain 3D model for the measurement of the full length of superior temporal sulcus S1 .Then cutting along the prependicular to the direction of the long axis of the temporal lobe with 1.0 mm spacings,the coronal sections were obtained,and the distance from superior temporal sulcus to temporal horn of lateral ventricle was ordinally measured and the shortest distance S2 was made sure.And the depth of superior temporal sulcus S3 was detected. The corresponding point on the surface of the brain at superior temporal sulcus according to the point leading the shortest distance S4 was determined. The ratio of S4 to S1 M was calculated. The angle between the shortest distance and median sagittal plane asαwas determined.All the samples were measured on both sides of the brain and all the data were compared.Results The S1 of the 120 cases was (159.56 ± 17.55)mm on the left and (164.35± 15.07)mm on the right,there was no statistical difference between two cerebral hemispheres(P>0.05);the S2 was (8.18±0.96)mm on the left and (7.81±0.90)mm on the right,there was no statistical difference between two cerebral hemispheres(P>0.05);the S3 was (12.19±1.43)mm on the left and (11.57± 1.33)mm on the right,there was no statistical difference between two cerebral hemispheres(P>0.05);the S4 was (100.88±16.09)mm on the left and (104.15±14.49)mm on the right,there was no statistical difference between two cerebral hemispheres(P>0.05);the M was (0.63 ±0.07)on the left and (0.63 ±0.06)on the right,there was no statistical difference between two cerebral hemispheres(P>0.05);theαwas (55.80±3.64)°on the left and (56.46±4.17)°on the right,there was no statistical difference between two cerebral hemispheres(P>0.05). Conclusion The point at the front side 3/5 of superior temporal sulcus may be the ideal surgical approach entrance point.The distance from the point to temporal horn of lateral ventricle is shortest.It indicates that the approach can reduce the damage of brain tissue.

OBJECTIVETo study the gene expression profiles of traumatic occlusion in early stage with the animal model of rats.

METHODSThe occlusal surface of the upper left first molar of rat was raised by placing a stainless steel wire to induce occlusal trauma in the lower left first molar. After 24 hours, the alveolar bone tissue of the first molars at the both sides of rats' lower jaws were taken out under anesthesia. The different expressive genes were shown by genome-wide microarray, which comprises about 27 000 genes and analyzed the different expressive genes with Pathway and GO analysis, finally the results of the microarray were examined by real time-polymerase chain reaction (RT-PCR).

RESULTSIn the results of the study, 586 different expressions were found, of which the expressions of 166 genes increased and 420 genes decreased. 106 different pathways were involved with Pathway analysis and 270 different functional classification related to GO analysis.

CONCLUSIONThe balance of the lower alveolar bone is destroyed after 24 hours of traumatic occlusion. At early phase of the occlusal trauma, osteogenesis and bone formation in alveolar bone are inhibited, yet osteoblast genesis and bone resorption are not significant.

Alveolar Bone Loss ; Animals ; Bone Resorption ; Dental Occlusion ; Dental Occlusion, Traumatic ; Mandible ; Molar ; Osteoblasts ; Osteogenesis ; Rats ; Transcriptome