Purpose To explore the clinicopathological and molecular genetic features of phytosterolemia(PTSL)with necrobiotic xanthogranuloma.Methods 4 cases of PTSL with necrobiotic xanthogranuloma as the primary mani-festation were reviewed.Gene mutations were detected by whole-exome sequencing and screened and verified by Sanger sequencing.The clinical manifestations,laboratory tests,genetic testing results,treatment and prognoses of the pa-tients were analyzed.Results All 4 patients developed subcutaneous masses on the face over a period of 3-13 years.Case 4 showed weakness of both lower limbs and an intracranial mass on MRI.Blood smear analysis revealed that the patients had platelets of varying sizes and were generally large,with increased stomatocytes.Total cholesterol(6.9-11.36 mmol/L)and low-density lipoprotein(4.45-7.08 mmol/L)were elevated in 4 patients.Genetic analysis re-vealed that cases 2 and 4 carried heterozygous mutations in the ABCG5 gene,and case 3 had a homozygous mutation in the ABCG8 gene.Conclusion Thrombocytopenia,stomatocytosis and splenomegaly are the special clinical manifesta-tions of patients with PTSL,and necrobiotic xanthogranuloma may be one of the late manifestations of the disease.Early genetic testing plays a critical role in the timely diagnosis and management of PTSL.

Purpose To explore the clinicopathological and molecular genetic features of phytosterolemia(PTSL)with necrobiotic xanthogranuloma.Methods 4 cases of PTSL with necrobiotic xanthogranuloma as the primary mani-festation were reviewed.Gene mutations were detected by whole-exome sequencing and screened and verified by Sanger sequencing.The clinical manifestations,laboratory tests,genetic testing results,treatment and prognoses of the pa-tients were analyzed.Results All 4 patients developed subcutaneous masses on the face over a period of 3-13 years.Case 4 showed weakness of both lower limbs and an intracranial mass on MRI.Blood smear analysis revealed that the patients had platelets of varying sizes and were generally large,with increased stomatocytes.Total cholesterol(6.9-11.36 mmol/L)and low-density lipoprotein(4.45-7.08 mmol/L)were elevated in 4 patients.Genetic analysis re-vealed that cases 2 and 4 carried heterozygous mutations in the ABCG5 gene,and case 3 had a homozygous mutation in the ABCG8 gene.Conclusion Thrombocytopenia,stomatocytosis and splenomegaly are the special clinical manifesta-tions of patients with PTSL,and necrobiotic xanthogranuloma may be one of the late manifestations of the disease.Early genetic testing plays a critical role in the timely diagnosis and management of PTSL.

Objective To investigate the clinicopathological features,immunophenotype,diagnosis and treatment of SMARCA4(BRG1)-deficient carcinoma.Methods Clinical data of 11 patients with SMAR-CA4(BRG1)-deficient cancer were collected.The morphologic and immunohistochemical features of this tumour were summarized,and the relevant literature was reviewed.Results Among the 11 cases of SMARCA4(BRG1)-deficient carcinoma,eight were male and three were female,with median age of 60.Seven patients underwent radical resection,and four underwent traditional joint targeted chemotherapy and immunotherapy.Microscopically,the tumor cells were epithelioid,rhabdoid or spindle-shaped,with prominent eosinophilic nucleoli and frequent mitoses(>5/10 HPF).Multiple foci of necrosis were found in the tumor tissue,a large number of tumor emboli in the blood vessels and myxoid stromal degeneration.Among these cases,11 cases showed loss of SMARCA4(BRG1)expression,whereas the CK and Vim markers were expressed,SMARCB1(INI1)expression was retained,and p53 mutation was detected.The tumor cells showed high proliferation activity(Ki-67>60%),and synaptophsin was moderately positive.Three cases were mismatch repair deficient and respectively showed the loss of MLH1/PMS2,PMS2 and MSH6 expression.Conclusion The incidence of SMARCA4(BRG1)-dificient carcinoma is low.It can be easily confused with other tumors and is difficult to be diagnosed before operation,which requires confirmation by immunohistochemistry.

Objective To investigate the effect of carbachol on local gut inflammation during entetal resuscitation of rats with bum shock. Method Thirty-eight Wistar rats were subjected to 35%TBSA full thickness scald injury, and enteral fluid was infused into animal intestines via duodenal stomas 30 minutes post bum. The animals were randomly divided into four groups: no resuscitation (Control, n = 8), enteral resuscitation using either a glucose electrolyte solution (GES, n = 10) or GES plus carbachol (60 μg·kg-1,GES/CAR, n = 10), or carbachol alone (CAR, n = 10) .The volumeof GES infusion was based on the Parkland formula (4 ml· 1% TB-SA-1·Kg-1) - All animals were sacrificed 4 hours post bum, and specimens of jejunal tissue were collected to determine the levels of tumor necrosis factor (TNF)-α, nitric oxide (NO), nitric oxide synthase (NOS) and myeloperoxidase (MPO). Serum assays for plasma diamine oxidase (DAO) activities were also performed. Results There were no statistical differences in the intestinal levels of NOS, NO, TNF-α and MPO, and plasma OAO activities, between the GES group and the control group. Compared to the GES group, the GES/CAR group showed significantly lowered levels of intestinal NOS (1.276 ±0.391 vs. 1.818 ±0.436, P＜0.05), NO (0.925 ±0.402 vs. 1.561 ±0.190, P ＜ 0.05, TNF-α (0.87±0.13 vs. 1.94±0.47, P ＜0.01) and MPO (0.465 ±0.092 vs. 0.832±0.214, P＜0.05),and reduction in plasma DAO activites (0.732±0.192 vs. 1.381 ±0.564, P ＜0.05). The CAR group also showed significantly lowered levels of intestinal NOS, NO, TNF-α and MPO and reduced plasma DAO activites, compared to the GES group. Conclusions Theses results suggest that carbachol significantly inhibits the release of proinflammatory mediator and attenuates local inflammation in gut during enteral fluid resuscitation of rats in rats with bum shock. We postulate that carbachol may exert its and-inflammatory effects via the cholinergic anti-inflammatory pathway.