Portal vein thrombosis (PVT) is one of the most common complications of liver cirrhosis. The formation of PVT can increase the mortality rate of cirrhotic patients and adversely affect the successful implementation and prognosis of liver transplantation. A hypercoagulable state is a unique mechanism underlying PVT formation in cirrhotic patients. In recent years, the pathogenesis of PVT has gradually been elucidated, with specific mechanisms including the following aspects: systemic and local inflammatory responses lead to vascular endothelial cell dysfunction, thereby promoting the activation of the coagulation system; abnormal activation of the monocyte-macrophage system exacerbates local inflammation, enhancing platelet adhesion and aggregation, and facilitating thrombus formation; an imbalance between the coagulation and fibrinolytic systems results in a sustained hypercoagulable state; and intestinal microbiota dysbiosis induces inflammation and metabolic disturbances, thereby increasing the risk of PVT. This article summarizes the latest research progress on these key mechanisms and their interactions, providing new insights into the molecular and cellular mechanisms of PVT. It also offers directions for the early diagnosis of PVT and the exploration of novel intervention strategies in the future.

AIM: To observe the changes of corneal densitometry(CD)in patients with keratoconus after corneal cross-linking(CXL).METHODS: Retrospective study. A total of 32 patients(43 eyes)with keratoconus in Ningxia Eye Hospital from April 2020 to April 2022 were selected. Pentacam analysis system divided the cornea into three layers: anterior 120 μm, middle layer and posterior 60 μm, and divides it into five regions with diameters of 0-2, 2-6, 6-10, 10-12 mm and full diameter according to the diameter, and measures the CD in different ranges. The changes of CD were compared before operation and at 1, 3 and 6 mo after operation.RESULTS: There were differences in uncorrected visual acuity, best corrected visual acuity and intraocular pressure before and 6 mo after operation(all P<0.05), and there was no difference in corneal endothelial cells(P=0.477). CD reached its peak at 1 mo after operation, and decreased at 3 mo and 6 mo after operation, but it was still higher than that before operation. There is a significant positive correlation between CD and Kmax in the anterior layer and the whole layer(r=0.164, P=0.016; r=0.152, P=0.023).CONCLUSION: The values of CD peaked at 1 mo after CXL, then it gradually decreased, tending to become stable at 6 mo postoperatively.

【Objective】 To explore the relationship between the methylation level of CNR1 and autism spectrum disorder (ASD), in order to provide a theoretical basis for the etiology of ASD. 【Methods】 A case-control study was conducted, recruiting 30 children with ASD from the Child Development and Behavior Research Center of Harbin Medical University and a rehabilitation facility, and 30 matched typically developed children from June 2017 to December 2018. The methylation levels of CNR1 in peripheral blood were measured by the Agena MassArray^® Mass Spectrometry System. A univariate conditional Logistic regression model was used to analyze the potential association between the methylation level of CNR1 and the risk of ASD with adjustment for age, BMI, body fat percentage and body fat. The correlations between the methylation level of CNR1 and the score of Social Responsiveness Scale (SRS) were evaluated by Pearson/Spearman correlation analysis. 【Results】 The methylation levels of the average methylation (t=2.224), CpG_3.4 (Z=2.187), CpG_9.10.11 (t=2.308), and CpG_28.29 (t=2.943) of the CNR1 promoter region in ASD children were significantly higher than controls (P<0.05). The methylation levels of the average methylation (OR=1.117, 95%CI: 1.003 - 1.245), CpG_9.10.11 (OR= 1.072, 95%CI:1.006 - 1.142), and CpG_28.29 (OR=1.078, 95%CI: 1.018 - 1.141) of the CNR1 promoter region were positively correlated with the risk of ASD (P<0.05). The methylation level of CpG_28.29 in ASD children was positively correlated with the scores of social motivation in SRS (r=0.421, P<0.05). 【Conclusions】 The methylation levels of CNR1 in peripheral blood are abnormal in ASD children and might be correlated with the risk of ASD and social function. The underlying mechanism needs to be further explored.

Objective:To investigate the preventive and therapeutic effects of compound wild chrysanthemum eye pad on blue light-induced alteration of meibomian gland function in mice and its mechanism.Methods:Sixty-four 15-week-old male C57BL/6J mice were divided into two groups of 32 mice each according to random numbers for the prevention test and the treatment test.The respective 32 mice in the prevention and treatment experiments were randomly divided into normal group, blue light group, solvent group and eye pad group according to random numbers, with eight mice in each group, respectively.In the prevention experiments, mice in each group were exposed to blue light at a wavelength of 460 nm and a light intensity of 2 000 lx for 6 hours per day for 15 consecutive days to establish a mouse model of meibomian gland function changes except for the normal group.The solvent group and the eye pad group were treated with the corresponding eye pad before and after the blue light exposure for 25 minutes daily for the 15 consecutive days.The blue light group was treated with blue light exposure only for 15 days, and the mice were photographed at the edge of the meibomian gland on day 15 to observe the function of the meibomian gland except for the normal group.In the treatment test, all groups of mice except the normal group were induced the altered function of the mouse meibomian gland by the above method.The solvent and eye pad groups were treated with corresponding eye pads for 25 minutes in the morning and afternoon of each day for 15 consecutive days after blue light exposure.The blue light group was kept in a standard environment for 15 days and the changes in meibomian gland function of mice were detected by meibomian gland photographs on day 15.Photography of the eyelid margin in vitro, oil red O staining, and hematoxylin-eosin staining were performed to observe the histologic changes in the meibomian glands of mice after the preventive and experimental treatment.The relative expression of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) mRNA in mouse meibomian gland tissues was detected by real-time fluorescence quantitative PCR.The expression of nuclear factor-κB (NF-κB) and phosphorylation of NF-κB (p-NF-κB) proteins in mice meibomian gland tissues was detected by Western blot to assess the degree of amelioration of blue light-induced inflammation in mouse meibomian glands by the compound wild chrysanthemum eye pad.This study was conducted in accordance with the Statement of the Association for Research in Vision and Ophthalmology on the Use of Animals in Ophthalmology and Vision Research, and was approved by the Animal Ethics Committee of Xiamen University (No.XMULAC20220258). Results:Compared with the normal group, a gradually increased number of blocked meibomian gland openings, and a gradually decreased remaining area of lower meibomian gland, were observed in the mice after 15 days of blue light group, and all the differences were statistically different (all at P<0.05). In the prevention test, the number of obstructed opening in the eye pad group was 1.833±0.753, which was significantly less than 3.667±1.033 in the solvent group ( P<0.05). The relative remaining area of the lower lid meibomian gland in the eye pad group was 0.718±0.091, which was significantly greater than 0.624±0.130 in the solvent group ( P<0.05). Hematoxylin-eosin staining showed inflammatory cell infiltration in mouse meibomian gland in the blue light and solvent groups.There was no inflammatory cell infiltration in eye pad group, and the morphology of the acini was similar to that of the normal group.Oil red O staining showed that there was no significant lipid deposition in the groups.The relative expressions of IL-1β, IL-6, TNF-α, and IFN-γ mRNA were significantly lower, and the relative expressions of NF-κB and p-NF-κB proteins were significantly lower in the eye pad group than in the solvent group, showing statistically significant differences (all at P<0.05). In the treatment test, the number of obstructed openings in the eye pad group and solvent group was 4.333±1.211 and 4.833±1.722, respectively, and the relative remaining area of the lower meibomian gland was 0.572±0.151 and 0.588±0.154, respectively, showing no statistically significant differences (both at P>0.05). Hematoxylin-eosin staining showed inflammatory cell infiltration in mouse meibomian glands in the blue light and solvent groups, with a similar morphology of acini as in the normal group.There was no inflammatory cell infiltration in eye pad group.Oil red O staining showed that there was no significant lipid deposition in the groups.The relative expressions of IL-1β, IL-6, and IFN-γ mRNA were significantly lower and the relative expressions of NF-κB and p-NF-κB proteins were significantly lower in the eye pad group than in the solvent group (all at P<0.05). Conclusions:Compound wild chrysanthemum eye pad may have preventive and therapeutic effects on blue light-induced changes in meibomian gland function by reducing the inflammatory response of meibomian gland tissue through the inhibition of the NF-κB signaling pathway.

To describe and evaluate the clinical studies of postoperative pain sensitization caused by sleep deprivation through the evidence map system, understand the distribution of evidence in this field, and provide reference for subsequent evidence research.

Objective:To retrospectively analyze the clinical phenotype and pathogenic variants in patients with Progressive myoclonus epilepsy (PME).Methods:Clinical data and results of genetic testing for 11 patients diagnosed with PME at the Department of Neurology, the First Affiliated Hospital of Zhejiang University School of Medicine from June 2017 to December 2022 were collected and analyzed.Results:All of the patients, including 4 males and 7 females, had predominant action myoclonus. Three patients had myoclonus as the initial manifestation, whilst eight were diagnosed through genetic testing, including three cases with NEU1 gene variants, two with EPM2A gene variants (1 was novel), one with MT- TK gene variant, one with ATN1 gene variant, and one with CSTB gene variant. No pathogenic variant was identified in the remaining three cases. Among the eight patients with a genetic diagnosis, three were diagnosed with sialidosis, two with Lafora disease, one with Dentatorubral-pallidoluysian atrophy (DRPLA), one with Unverricht-Lundborg disease (ULD), and one with Myoclonic epilepsy with ragging red fibers (MERRF). Conclusion:Compared with pediatric patients, adult patients with PME represent a distinct subtype with slower progression and milder cognitive impairment.

Objective To explore the mechanism of ginsenoside Rg1 in alleviating heat stress-induced testicular injury in mice.Methods A total of 20 C57BL/6 male mice(6～8 weeks old)were randomly divided into 4 groups(n=5).The mice from the control group and heat stress(HS)group were intraperitoneally injected with 10 mL/(kg·d)0.9％normal saline for 14 d,while those in the HS+Rg1 group and the Rg1 group were given an intraperitoneal injection of 20 mg/(kg·d)for 14 d,and then on the 7th day after administration,the mice in the HS group and the HS+Rg1 group had the lower abdomen put into a 43 ℃ water bath for 30 min as a single heat stress after being anesthetized with 4％chloral hydrate.Mouse spermatocytes GC-2spd(ts)were divided into control group(routine culture for 48 h),HS group(placed in a 43 ℃ water bath for 30 min after 36 h of conventional culture,and cultured till the end of 48 h),HS+Rg1 group(50 μmol/L Rg1 treatment followed by heat stress injury),and Rg1 group(no heat stress injury).In 1 d after modeling,the eyeball blood samples were collected to detect serum testosterone with ELISA,and the testicles were extracted to observe the morphology and weighed to calculate the testicular index.HE staining was used to observe the histopathology of testis,and corresponding reagents and kits was employed to detect the content of malondialdehyde(MDA)and activities of catalase(CAT)and superoxide dismutase(SOD)in testis tissue.After the epididymal sperm were collected,the sperm concentration and motility were analyzed by computer-assisted sperm analysis(CASA)system.In in vitro experiments,cell apoptosis was detected with TUNEL staining,the protein levels of Nrf2,Keap1,HO-1,Bax,Bcl-2 and Caspase3 were detected with Western blotting,and the mRNA levels of GCLC,GCLM and NQO1 were detected by RT-qPCR.Results Rg1 prevented the decreases in testicular weight and testicular index caused by heat stress,reduced the damage of testicular tissue structure,prevented the decrease of sperm concentration and vitality,antagonized the decreasd number of Leydig cells and serum testosterone level,reduced the accumulation of MDA in testicular tissue,and enhanced the activities of CAT and SOD.Rg1 treatment alleviated the apoptosis of GC-2spd(ts)cells,down-regulated the expression of Bax,Caspase3 and Keap1 proteins,enhanced the expression of Bcl-2,Nrf2 and HO-1 proteins,and increased the transcriptional levels of Nrf2 target genes GCLC,GCLM and NQO1.Conclusion Rg1 has no significant effect on the structure and function of mouse testes,but it can effectively improve the ability of mouse testes to resist heat stress injury,which may be related to the activation of Nrf2 signaling pathway,the improvement of antioxidant enzyme activity,and the reduction of apoptosis of spermatogenic cells.

Objective:To investigate the expression of programmed cell death ligand 1 (PD-L1), clinicopathologic features, immunohistochemical expression and molecular characteristics in fumarate hydratase (FH)-deficient renal cell carcinoma and to explore the potential application of immunotherapy in the patients.Methods:There were six patients with FH-deficient renal cell carcinoma treated at the First Affiliated Hospital of Fujian Medical University between January 2020 and October 2022. The clinical data, histological morphology, immunophenotype, PD-L1 expression and next-generation sequencing results were tabulated and analyzed.Results:There were 6 patients, all male, age ranged from 37 to 72 years (mean 45.7 years). Four cases were high-grade (WHO/ISUP grade3-4) with 2 or more histologic patterns, including papillary (most common), glandular, tubular, vesicular, ethmoid, nest-like, cystic and solid structures. Two cases were low-grade which showed nest-like, glandular, or tubular arrangement with eosinophilic flocculent cytoplasm and small intracellular vacuoles. Immunohistochemical analysis revealed strong expression of 2SC in all 6 cases, negative expression of FH in 5 cases, and positive expression of GATA3 in 5 cases. In high-grade cases, the mean values of CD4 and CD8 positive T-lymphocytes in advanced tumor invasion were 180.3/mm 2 and 130.5/mm 2, respectively. PD-L1 combined positive scores (CPS) were 20, 50, 5 and 30, respectively. The Ki-67 proliferative index were 20%, 20%, 10% and 30%, respectively. In low-grade cases, the mean values of CD4 and CD8 positive T-lymphocytes were 123.0/mm 2 and 100.5/mm 2, respectively. The PD-L1 CPS score was 1, and the Ki-67 proliferation index was 3%. High-throughput sequencing showed FH gene somatic mutation in 3 cases, FH gene germline mutation in 2 cases, and FH gene mutation was not detected in one case. Conclusion:FH-deficient renal cell carcinoma is more commonly high-grade than low grade. FH and 2SC are immunohistochemical markers used in the diagnosis of FH-deficient renal cell carcinoma, and GATA3 positivity is supportive of the diagnosis. The tumor infiltration of high-grade FH-deficient renal cell carcinoma shows an increase in CD4 and CD8 positive T-lymphocytes, and high expression of PD-L1; thus, anti-PD-L1 immunotherapy can be used as a treatment option.

Objective To investigate the clinical application value of MRI Radiomics score(Radscore)combined with clinicopatho-logical features in predicting postoperative progression-free survival(PFS)of patients with endometrial cancer(EC).Methods A total of 127 patients with EC were selected.The radiomic features of the lesions were extracted from T2 WI,diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)images.The features were screened by random forest model and Radscore was calcu-lated.Simultaneously,clinical and pathological characteristics of patients were collected and incorporated,and multivariate Cox regression analysis was used to screen the risk factors related to PFS.The MRI Radscore and clinicopathological features were mapped to the nomogram,and the performance of nomogram was evaluated by receiver operating characteristic(ROC)curve and calibration curve.Results Multivariate Cox regression analysis showed that progesterone receptor(PR),human epididymis protein 4(HE4)and MRI Radscore were independent risk factors for predicting PFS in patients with EC(P＜0.05).The area under the curve(AUC)of the predicted PFS at 1,3 and 5 years after surgery were 0.91,0.804 and 0.776,respectively.Calibration curves showed that nomogram had a good fit in predicting PFS in patients with EC 1,3 and 5 years after surgery.Conclusion The nomogram con-structed based on multi-sequence MRI Radscore and clinicopathological features has favorable accuracy and stability in predicting postoperative PFS in individuals diagnosed with EC.

Objective:To retrieve, evaluate and summarize relevant evidence on home-based exercise management in patients with mild to moderate Parkinson's disease, so as to provide reference and guidance for clinical healthcare professionals to construct and improve patient home-based exercise intervention plans.Methods:According to the top-down principle of the "6S" evidence model, UpToDate, BMJ, National Institute for Health and Clinical Excellence, Guidelines International Network, National Guideline Clearinghouse, Medlive, Clinical Guidelines Network, Joanna Briggs Institute, Cochrane Library, PubMed, CINAHL, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Data, VIP and China Biology Medicine Disc were systematically searched for relevant literature on home-based exercise management in patients with Parkinson's disease, including guidelines, expert consensuses, systematic reviews, evidence summaries, clinical decisions, recommended practices and best practices. The search period was from the establishment of the databases to October 31, 2022. Two researchers independently evaluated the quality of the literature and extracted and integrated evidence.Results:A total of 27 articles were included, including three guidelines, five expert opinions and consensuses, three clinical practice suggestions, 15 systematic evaluations and one clinical decision. A total of 45 pieces of evidence were summarized from six aspects, such as organizational management, health education, exercise evaluation, exercise prescription, family and social support and monitoring guidance.Conclusions:This study summarized the best evidence of home-based exercise management for patients with mild to moderate Parkinson's disease, which can provide evidence-based basis for clinical staff to formulate home-based exercise management programs and standardize practice standards.