As a crucial link in the progression of various chronic liver diseases to liver cirrhosis,liver fibrosis affects the prognosis and outcome of chronic liver diseases.Necrotosis is a novel pattern of programmed cell death(PCD),and studies have shown that it plays an important role in the pathophysiology of various diseases and is considered a potential target for improving liver fibrosis.Necroptosis of various types of intrahepatic cells(including hepatocytes,hepatic stellate cells,liver macrophages,and hepatic sinusoidal endothelial cells)can promote or inhibit liver fibrosis.This article elaborates on the above mechanisms and discusses the therapeutic strategies for targeting liver fibrosis mediated by necroptosis.

Objective:To explore the clinicopathological characteristics of primary bladder mucosal-associated lymphoid tissue extranodal marginal zone lymphoma (MALToma).Methods:A retrospective case series study was conducted. The clinicopathological data of 9 primary bladder MALToma patients diagnosed and underwent transurethral resection of bladder tumors at the Fujian Provincial Hospital, Zhangzhou Municipal Hospital, Mindong Hospital of Ningde City, Zhangzhou Second Hospital and Fuzhou Taijiang Hospital from December 2008 to December 2021 were collected. Paraffin-embedded surgical specimens were collected for HE staining, immunohistochemical staining and genetic testing, the clinicopathological characteristics of patients were summarized, and the literature was reviewed.Results:Of the 9 cases, 8 were female and 1 was male, the age was (59± 11) years old (range: 39-74 years old). Two cases had 3 lesions, 3 cases had 2 lesions, and 4 cases had single lesion. The maximum diameter of the mass was (3.2±1.9) cm (range: 0.3-7.0 cm). The follow-up time was 6-127 months, 4 cases lost to follow-up, 4 cases were disease-free survival, and 1 case was survival with tumor. Pathomorphologically, the bladder tissue consisted of diffusely infiltrating small-to-medium sized lymphocytes, with moderate amounts of pale-staining cytoplasm, without obvious nucleoli, some of them were translucent, and the mitosis was rare. Large cell proliferation in some areas was observed in 1 case, with prominent nucleoli and mitotic figures. Tumor cells in all 9 patients expressed CD20; bcl-2, CD43 and CD38 were positive in some cells in 4 cases, and CD138 was positive in a few cells in 2 cases; κ was positive in 4 cases, and scattered positive in 5 cases; λ was positive in 4 cases, and scattered positive in 5 cases. B-cell receptor gene clonal rearrangement was positive in all 8 cases who underwent the assay. No break-apart signal was observed in all 6 cases who underwent the fluorescence in situ hybridization assay with MALT1 gene segregation probe.Conclusions:Primary bladder MALToma is a rare low-grade B-cell lymphoma that is more commonly found in elderly women. There is no abnormal change in MALT1 gene.

Objective:To evaluate the predictive value of preoperative frailty combined with nutritional status for prolonged postoperative ileus (PPOI) in the patients with gynecological malignancies.Methods:Patients undergoing elective surgery for gynecological malignancies in the Affiliated Hospital of Jiangnan University from April 2022 to February 2023 were selected. The Frail scale was used to evaluate the frailty within 24 h of admission, and the nutritional status was evaluated by the Controlling Nutritional Status score. The general characteristics of patients and occurrence of PPOI were recorded, and the risk factors for PPOI were analyzed by multivariate logistic regression. The ability of frailty, nutritional status and their combination to predict PPOI was assessed by the receiver operating characteristic curve.Results:Two hundred and fourteen patients were finally included, 52 cases developed of PPOI, and 98 cases were frail patients. Preoperative frailty combined with moderate to severe malnutrition was an independent risk factor for PPOI in the patients with gynecological malignancies ( P<0.05), and the area under the curve in predicting the occurrence of PPOI was 0.796 (95% confidence interval 0.736-0.857) in the patients with gynecological malignancies. Conclusions:Preoperative frailty combined with moderate to severe malnutrition has a higher accuracy in predicting PPOI in the patients with gynecological malignancies.

Objective:To investigate the expression levels of serum miR-126 and miR-9 in patients with wet age-related macular degeneration (wAMD) and their relationship with vascular endothelial growth factor (VEGF) and central macular thickness (CMT).Methods:A total of 73 wAMD patients(observation group) admitted to the ophthalmology department of Taizhou Municipal Hospital from May 2020 to May 2021 and 60 healthy subjects (control group) who underwent physical examination during the same period were selected. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-126 and miR-9 in serum of the two groups. Serum angiogenesis regulatory factors [VEGF, tissue inhibitor of melalloproteinuses-1 (TIMP-1), endostatin (ES), platelet-derived growth factor (PDGF)] were detected by enzyme-linked immunosorbent assay (ELISA), and CMT and intraocular pressure (IOP) were measured. Pearson correlation analysis was performed to determine the correlation between miR-126 and miR-9 and serum angiogenesis regulatory factor levels, CMT and IOP. The diagnostic value of miR-126 and miR-9 in wAMD was analyzed by receiver operating characteristic (ROC) curve.Results:The relative expression level of serum miR-126 in observation group was significantly lower than that in control group ( P<0.05) , while the relative expression level of serum miR-9 was significantly higher than that in control group ( P<0.05). The levels of serum VEGF and PDGF in observation group were significantly higher than those in control group (all P<0.05), while the levels of serum TIMP-1 and ES were significantly lower than those in control group (all P<0.05). CMT and IOP in observation group were significantly higher than those in control group (all P<0.05). The expression level of serum miR-126 in observation group was negatively correlated with serum VEGF, PDGF, CMT and IOP ( r=-0.275, -0.523, -0.302, -0.542, all P<0.05), and was positively correlated with TIMP-1 and ES ( r=0.460, 0.263, all P<0.05). Serum miR-9 expression level was positively correlated with serum VEGF, PDGF, CMT and IOP ( r=0.434, 0.438, 0.396, 0.307, all P<0.05), and was negatively correlated with TIMP-1 and ES ( r=-0.256, -0.310, all P<0.05). The area under curve (AUC) values of serum miR-126 and miR-9 in diagnosing wAMD were 0.713 and 0.847 respectively. Conclusions:The expression level of serum miR-126 is significantly decreased while the expression level of miR-9 is significantly increased in patients with wAMD. miR-126 is negatively correlated with VEGF and CMT, and miR-9 is positively correlated with VEGF and CMT, which may aggravate the disease by promoting the inflammatory response. The detection of expression levels of serum miR-126 and miR-9 is helpful to provide the reference basis for early diagnosis of wAMD and early prevention and treatment.

The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to inves-tigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.

Background: Diabetes can complicate hypertension management by increasing the risk of cardiovascular disease (CVD) and all-cause mortality. Studies targeting diabetes detection in hypertensive individuals demonstrating an increased risk of diabetes are lacking.We aimed to assess the performance of hemoglobin A1c (HbA1c) and its cut-off point in detecting diabetes in the abovementioned population. Methods: Data from 4,096 community-dwellers with hypertension but without known diabetes were obtained from the Study on Evaluation of iNnovated Screening tools and determInation of optimal diagnostic cut-off points for type 2 diaBetes in Chinese muLti-Ethnic (SENSIBLE) study; these data were randomly split into exploration (70% of the sample) and internal validation (the remaining 30%) datasets. The optimal HbA1c cut-off point was derived from the exploration dataset and externally validated using another dataset from 2,431 hypertensive individuals. The oral glucose tolerance test was considered the goldstandard for confirming diabetes. Results: The areas under the ROC curves for HbA1c to detect diabetes were 0.842, 0.832, and 0.829 for the exploration, internal validation, and external validation datasets, respectively. An optimal HbA1c cut-off point of 5.8% (40 mmol/mol) yielded a sensitivity of 76.2% and a specificity of 74.5%. Individuals who were not diagnosed as having diabetes by HbA1c at 5.8% (40 mmol/mol) had a lower 10-year CVD risk score than those diagnosed as having diabetes (P = 0.01). HbA1c ≤ 5.1% (32 mmol/mol) and ≥ 6.4% (46 mmol/mol) could indicate the absence and presence of diabetes, respectively. Conclusions HbA1c could detect diabetes effectively in community-dwellers with hypertension.

Objective:To investigate the clinicopathological features, diagnosis, differential diagnosis and immunohistochemical (IHC) characteristics of paraganglioma of urinary bladder (PUB).Methods:The clinical and pathological data of 23 cases of PUB were collected at the Second Affiliated Hospital of Fujian Medical University (7 cases); Fujian Provincial Hospital (8 cases); Fujian Medical University Union Hospital (6 cases); and First Affiliated Hospital of Fujian Medical University (2 cases) from May 2010 to November 2018. IHC staining for CK, GATA3, CD56, Syn, CgA, S-100 protein, HMB45, SDHB, OCT3/4 and Ki-67 was done using EliVision method; and the relevant literature was reviewed.Results:There were 14 women and 9 men, aged ranged from 21 to 73 years (median 51 years). Clinically, patients presented with headache, vertigo, palpitation, hypertensive crisis during micturition, hypertension, blurred vision, gross hematuria and paroxysmal pallor. The tumor sizes ranged from 0.9 to 6 cm (mean2.5 cm). Macroscopically, most tumors were exophytic and well delineated within the lamina propria or muscularis propria. The tumors were firm and nodular and showed grayish-tan cut surface. Histologically,the tumor growth pattern was expansive or showed interpenetrating infiltrative growth within the lamina propria or muscularis propria; the tumor cells were typically arranged in distinctive nests (Zellballen) with organoid arrangement; pseudo-rosette were seen in some cases. The cells were rounded or polygonal and had rich, acidophilic or amphophilic cytoplasm and may contain pigmented granules and vacuoles; the nuclei were central or eccentric, with small nucleoli, although occasionally some nuclei were pleomorphic and hyperchromatic. Spindled sustentacular cells could be seen around the nests of tumor cells in some cases. There were abundant vessels that were fissure-like, hemangioma-like or dilated. By IHC, the tumor cells were positive for GATA3 (2/23), OCT3/4 (2/23), CD56 (22/23), Syn (23/23), CgA (22/23), S-100 (sustentacular cell, 23/23) and SDHB (23/23); and negative for CK and HMB45; Ki-67 index was 1%-5%. At follow-up, there was no recurrence or metastasis in 18 cases.Conclusions:The diagnosis of PUB relies on the morphologic and IHC features; but there may be histomorphologic heterogeneity. The most important differential diagnosis is invasive urothelial carcinoma. The tumor cells may show aberrant cytoplasmic expression of OCT3/4; there is no clear correlation between SDHB and OCT3/4 expression in the group.

Objective:To investigate the clinicopathological characteristics, immunophenotype, molecular genetic characteristics and prognosis of the metaplastic thymoma (MT).Methods:The clinicopathological and follow-up data of five MT cases were collected at Fujian Provincial Hospital from 2008 to 2019. Immunohistochemical staining and MAML2 gene detection were performed, and the relevant literature was reviewed.Results:There were 2 males and 3 females, aged 36-64 years (mean age 52 years). The tumors ranged 3.2-7.3 cm in the greatest diameter (average 5.1 cm).Microscopically, the tumor showed a biphasic pattern with epithelial cells merging gradually with the spindle cell component. The two areas transited to each other or had obvious boundary. Both components showed mild atypia. No mitosis was observed in either area, and a small number of lymphocytes were observed in the stroma. Immunohistochemical staining showed that epithelioid cells were positive for CKpan, p63 and E-cadherin. Spindle cells were positive for vimentin and EMA, while the Ki-67 index was less than 5%, and lymphocytes were negative for TdT. MAML2 gene apart signal was detected in two of the cases (2/4) that were tested by FISH.Conclusions:MT is a low-grade malignant epithelioid thymic tumor. Its diagnosis and differential diagnosis are dependent on the morphological characteristics, immunohistochemical staining and MAML2 gene detection. The primary treatment option is surgical resection, with an overall good prognosis.

Objective To compare the dose distribution between volumetric-modulated arc therapy ( VMAT ) and intensity-modulated radiotherapy ( IMRT ) in patients with brain metastases receiving hippocampus-sparing whole brain radiotherapy. Methods Forty-six patients with brain metastases admitted to our hospital from 2013 to 2016 were recruited in this study. After fusing the CT and MRI images, the hippocampus was delineated on the fusion images. The three-grade hippocampal avoidance regions were created by using a volumetric expansion of 3,5 and 10 mm surrounding the hippocampus. The planning target volume ( PTV) was calculated by subtracting the 5-mm expansion surrounding the hippocampus from the whole brain. The prescription dose was 30 Gy/10 fractions. The 7-field IMRT and single arc VMAT were designed for each case. The dose distribution of PTV,hippocampus and other organs at risk ( OARs) were evaluated in both plans. Results The PTV was statistically compared between VMAT and IMRT:V95:95. 90％ and 94. 97％( P=0. 000 );V90:98. 17％ and 97. 48％( P=0. 000 );CI:0. 825 and 0. 813 ( P=0. 013);HI:0. 277 and 0. 289(P=0. 025).The hippocampal dose was also compared between VMAT and IMRT:the Dmax of hippocampus was 1698. 9 cGy for VMAT and 1784. 9 cGy for IMRT (P=0. 002).TheDmean of hippocampus was 1183. 8 cGy for VMAT and 1112. 7 cGy for IMRT (P=0. 000).No statistical significance was observed between IMRT and VMAT in protecting the OARs except the chiasma opticum ( 3262. 6 cGy and 3529. 3 cGy,P=0. 000).The MU and treatment time of VMAT and IMRT were 651 and 2768( P=0. 000) ,and 188 s and 504 s ( P=0. 000) . Conclusions The dose distribution of PTV in VMAT is significantly better than that in IMRT. VMAT is advantageous in protecting the hippocampus than IMRT. VMAT can significantly shorten treatment time and MU and enhance the equipment utilization. Besides, VMAT can achieve the goal of protecting the hippocampus and meet the prescription dose requirement of PTV.

OBJECTIVETo explore the clinical features and mutation of TGFBI gene in a Chinese pedigree affected with lattice corneal dystrophy (LCD).

METHODSGenomic DNA was extracted from 35 members including 11 patients from the pedigree. The 17 exons and splicing region of introns of the TGFBI gene were amplified by PCR. The products were directly sequenced and compared with GenBank database to identify potential mutation. Bioinformatic analysis was carried out to predict the effect of mutation on proteins.

RESULTSA heterozygous mutation (p.R124C) was found in exon 4 of the TGFBI gene in all patients from the pedigree but not among unaffected members. The mode of inheritance of corneal dystrophy in this pedigree was identified as autosomal dominant. Bioinformatics analysis predicted that the p.R124C mutation may be functionally deleterious. The phenotype of corneal dystrophy in the pedigree was determined to be LCD I type.

CONCLUSIONThe p.R124C mutation of the TGFBI gene probably underlies the pathogenesis of LCD in this Chinese pedigree. Genetic testing can facilitate proper diagnosis of this type of corneal dystrophy.