Purpose This study aimed to investigate the expression and clinical significance of TLDC2 in colorec-tal adenocarcinoma.Methods Data from the human protein atlas(HPA)and the cancer genome atlas(TCGA)indi-cated that TLDC2 was highly expressed in colorectal adenocarcinoma.We further analyzed the expression of TLDC2 in 400 colorectal adenocarcinomas and 447 other solid tumors using tissue microarrays and immunohistochemical(IHC)staining.Result The positive expression rate of TLDC2 was significantly higher than that of SATB2 in colorectal ade-nocarcinomas(96.5％vs 87.0％,P＜0.000 1).TLDC2 positivity exceeded that of SATB2 in both low-or high-grade colorectal adenocarcinoma(99.4％vs 88.7％,P＜0.000 1;83.3％vs 79.2％,P=0.669 9).In addition,the expression of TLDC2 and SATB2 was evaluated in 447 cases of other types of solid tumors.TLDC2 was expressed in neuroendocrine tumors as well as in gastric and appendiceal adenocarcinomas,whereas SATB2 was detected in a small number of melanomas,ovarian cancers,breast cancers and gallbladder cancers.The positive and specificity of TLDC2 for colorectal adenocarcinoma were 97％(95％CI=0.94-0.98)and 85％(95％CI=0.81-0.88),respectively.Combined detection of TLDC2 and SATB2 yielded a sensitivity of 96％(95％CI=0.93-0.97)and a specificity of 93％(95％CI=0.90-0.95).Conclusion Analysis of large-scale datasets and IHC staining demonstrated that TLDC2 is a highly sensitive and specific biomarker for colorectal adenocarcinoma.

Purpose To investigate the clinicopathological features,diagnosis,and molecular genetic characteris-tics of central nervous system(CNS)high-grade neuroepithelial tumors with BCOR alterations.Methods Five cases of CNS high-grade neuroepithelial tumors harboring BCOR alterations were collected.Using immunohistochemistry and molecular detection to analyze its clinical and histological characteristics,and review relevant literatures.Results A-mong the 5 patients,3 cases with EP300 ∷ BCOR tumor(male-to-female ratio 2∶1).These tumors were located in supratentorial regions(right temporal lobe,right frontotemporal lobe,and right frontal lobe).The 2 patients with BCOR-ITD tumors were younger,both with tumors located in the left cerebellum.Imaging studies revealed well-defined large mass lesions in all cases.Histologically,all 5 cases tumor exhibited ependymoma-like or oligodendroglioma-like morphology,featuring uniformly oval or round cells.Focal areas showed increased cellular density,nuclear enlarge-ment,and readily identifiable mitotic figures indicative of anaplastic features.A rich capillary network was frequently observed in the stroma.Palisading necrosis,microcystic changes,and microcalcifications were present in 3 cases.Im-munohistochemically,all 5 cases consistently expressed vimentin and CD56,focal Olig-2 positivity,variable S-100 ex-pression,and were uniformly negative for GFAP.BCOR immunostaining was weakly positive in 1 case with an EP300∷ BCOR fusion and strongly positive in 2 cases with BCOR-ITD.NGS identified an EP300 ∷ BCOR fusion in 3 cases,and Sanger sequencing confirmed the ITD in exon 15 of BCOR gene in 2 cases.During a follow-up period of 8 to 77 months,one pediatric patient with a BCOR-ITD tumor died,while the remaining four patients were alive with no evi-dence of recurrence or metastasis.Conclusion BCOR-ITD and EP300 ∷ BCOR fusion tumors are similar in morphology and immunophenotype,and the incidence rate of BCOR fusion tumors may be underestimated.NGS sequencing based on DNA and RNA and DNA methylation spectrum analysis are helpful for accurate diagnosis of this type of tumor.

Purpose To investigate the clinicopathological features,diagnosis,and molecular genetic characteris-tics of central nervous system(CNS)high-grade neuroepithelial tumors with BCOR alterations.Methods Five cases of CNS high-grade neuroepithelial tumors harboring BCOR alterations were collected.Using immunohistochemistry and molecular detection to analyze its clinical and histological characteristics,and review relevant literatures.Results A-mong the 5 patients,3 cases with EP300 ∷ BCOR tumor(male-to-female ratio 2∶1).These tumors were located in supratentorial regions(right temporal lobe,right frontotemporal lobe,and right frontal lobe).The 2 patients with BCOR-ITD tumors were younger,both with tumors located in the left cerebellum.Imaging studies revealed well-defined large mass lesions in all cases.Histologically,all 5 cases tumor exhibited ependymoma-like or oligodendroglioma-like morphology,featuring uniformly oval or round cells.Focal areas showed increased cellular density,nuclear enlarge-ment,and readily identifiable mitotic figures indicative of anaplastic features.A rich capillary network was frequently observed in the stroma.Palisading necrosis,microcystic changes,and microcalcifications were present in 3 cases.Im-munohistochemically,all 5 cases consistently expressed vimentin and CD56,focal Olig-2 positivity,variable S-100 ex-pression,and were uniformly negative for GFAP.BCOR immunostaining was weakly positive in 1 case with an EP300∷ BCOR fusion and strongly positive in 2 cases with BCOR-ITD.NGS identified an EP300 ∷ BCOR fusion in 3 cases,and Sanger sequencing confirmed the ITD in exon 15 of BCOR gene in 2 cases.During a follow-up period of 8 to 77 months,one pediatric patient with a BCOR-ITD tumor died,while the remaining four patients were alive with no evi-dence of recurrence or metastasis.Conclusion BCOR-ITD and EP300 ∷ BCOR fusion tumors are similar in morphology and immunophenotype,and the incidence rate of BCOR fusion tumors may be underestimated.NGS sequencing based on DNA and RNA and DNA methylation spectrum analysis are helpful for accurate diagnosis of this type of tumor.

Purpose This study aimed to investigate the expression and clinical significance of TLDC2 in colorec-tal adenocarcinoma.Methods Data from the human protein atlas(HPA)and the cancer genome atlas(TCGA)indi-cated that TLDC2 was highly expressed in colorectal adenocarcinoma.We further analyzed the expression of TLDC2 in 400 colorectal adenocarcinomas and 447 other solid tumors using tissue microarrays and immunohistochemical(IHC)staining.Result The positive expression rate of TLDC2 was significantly higher than that of SATB2 in colorectal ade-nocarcinomas(96.5％vs 87.0％,P＜0.000 1).TLDC2 positivity exceeded that of SATB2 in both low-or high-grade colorectal adenocarcinoma(99.4％vs 88.7％,P＜0.000 1;83.3％vs 79.2％,P=0.669 9).In addition,the expression of TLDC2 and SATB2 was evaluated in 447 cases of other types of solid tumors.TLDC2 was expressed in neuroendocrine tumors as well as in gastric and appendiceal adenocarcinomas,whereas SATB2 was detected in a small number of melanomas,ovarian cancers,breast cancers and gallbladder cancers.The positive and specificity of TLDC2 for colorectal adenocarcinoma were 97％(95％CI=0.94-0.98)and 85％(95％CI=0.81-0.88),respectively.Combined detection of TLDC2 and SATB2 yielded a sensitivity of 96％(95％CI=0.93-0.97)and a specificity of 93％(95％CI=0.90-0.95).Conclusion Analysis of large-scale datasets and IHC staining demonstrated that TLDC2 is a highly sensitive and specific biomarker for colorectal adenocarcinoma.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To explore the effect and the possible mechanism of knockdown acetyl CoA carboxylase 1(ACC1)on the migration of KYSE450 cells.Methods KYSE450 cells during the logarithmic phase were randomly divided into the shNC group,shACC1 group,shNC+AEB071 group,and shACC1+AEB071 group.The KYSE450 cells in the shNC group were transfected with empty plasmid;the KYSE450 cells in the shACC1 group were transfected with lentiviral plasmid;the KYSE450 cells in the shNC+AEB071 group were transfected with empty plasmid and then added with 5 μL of 2 mmoL·L-1 protein kinase C(PKC)inhibitor AEB071(final concentration 5 μmoL·L-1);The KYSE450 cells in the shACC1+AEB071 group were transfected with lentiviral plasmid and then added with 5 μL of 2 mmoL·L-1 PKC inhibitor AEB071(final concentration 5 μmoL·L-1).The migration of KYSE450 cells was detected by Transwell assay.The morpho-logical changes of KYSE450 cells were observed under the microscope.The expression levels of ACC1,histone H3(H3),histone H3 lysine 9 acetylation(H3K9Ac),and epithelial-mesenchymal transition(EMT)markers such as β-catenin,Vimentin and Snail were measured by Western blot.Results The migration of KYSE450 cells in the shACC1 group was significantly higher than that in the shNC group(P＜0.05);there was no significant difference in the migration ability of KYSE450 cells between the shNC+AEB071 group and the shNC group(P＞0.05);the migration of KYSE450 cells in the shACC1+AEB071 group was significantly lower than that in the shACC1 group(P＜0.05).The KYSE450 cells in the shNC group revealed an elliptical epithelial-like cell morphology;the KYSE450 cells in the shACC1 group exhibited a spindle-like interstitialcell morphology;the KYSE450 cells in the shNC+AEB071 and shACC1+AEB071 groups showed an elliptical epithelial-like cell morphology.The relative expression level of ACC1 in KYSE450 cells in the shACC1 group was significantly lower than that in the shNC group(P＜0.05),while the relative expression levels of β-catenin,Vimentin and Snail as well as the ratio of H3K9Ac/H3 were significantly higher than those in the shNC group(P＜0.05);the relative expression levels of ACC1,β-catenin,Vimentin and Snail as well as the ratio of H3K9Ac/H3 showed no significant difference between the shNC+AEB071 group and the shNC group(P＞0.05);the relative expression levels of β-catenin,Vimentin and Snail as well as the ratio of H3K9Ac/H3 in the shACC1+AEB071 group were significantly lower than those in the shACC1 group(P＜0.05);there was no significant difference in the relative expression level of ACC1 in KYSE450 cells between the shACC1+AEB071 group and the shACC1 group(P＞0.05).Conclusion Knockdown of ACC1 promotes migration of KYSE450 cells and thus aggravates the tumor,which may be mediated by PKC-related signaling pathways.

Purpose To investigate and summarize the clinicopathological features,immunophenotype,diagnosis and differential diagnosis of anaplastic thyroid carcinoma(ATC).Methods The clinicopathological features and follow-up data of 15 patients with ATC were reviewed and retrospectively ana-lyzed,and the histological features,immunophenotypic,and molecular features were observed.Results There were 8 males and 7 females with a mean age of 63.5 years.The largest tumor diameter was 45.9 mm(range,20-73 mm).Macroscopically,the tumors appeared nodular or lobulated,mostly firm to hard,with a cut surface of gray-white or gray-yellow in color,and were accompanied by hemorrhage,necrosis,and cystic changes.Mi-croscopically,the tumor exhibited diverse structures and cellular morphology mainly composed of epithelioid,spindle,multinu-cleated giant cells,rarely rhabdoid morphology(2 cases)and heterologous osteosarcomtoid differentiation(1 case).Two cases showed squamous cell carcinoma morphology as well.Among them,there were pure ATC in 11 cases while three cases had mixed papillary thyroid carcinoma components and one case had coexisting high-grade differentiated thyroid carcinoma compo-nent.Cervical lymph node metastasis was present in 6 cases.CK(AE1/AE3)expression was observed in 80%of the cases while PAX8 expression was seen in53.3%.Varying degrees of BRAF(VE1)expression were found in 42.9%whereas weak focal TTF-1 expression occurred only in two cases;and all cases did not express TG.Overall,genetic testing was performed in 8 cases(53.3%).The TP53 gene was the most frequently muta-ted gene(5/8,62.5%),followed by the RAS(3/8,37.5%)and BRAF(3/8,37.5%)genes,while the TERT combined with PIK3CA gene was mutated in only one case.Moreover,multiple gene mutations occurred simultaneously in five cases.Of the total fourteen patients who underwent follow-up,the mean and median survival times were 13.9 and 5.0 months,respec-tively.The disease-specific mortality rate reached 78.6%.Conclusion ATC is extremely rare,displaying unique histolog-ical characteristics,often accompanied by various gene muta-tions.It has a poor prognosis;therefore,establishing a defini-tive pathological diagnosis provides valuable evidence for predic-ting patient outcomes and guiding clinical management.

【Objective】 To investigate the factors affecting the quality of cryoprecipitated antihemophilic factor. 【Methods】 The quality test results of cryoprecipitated antihemophilic factor in Xuzhou Central Blood Station from 2017 to 2020 were selected and compared. The fresh frozen plasma (FFP) was stratifying by storage time following whole blood collection: less than 2h, 2~4 h, 4~6 h, and 6~8 h; by gender: males and females; by blood group: A, B, O, and AB groups; by age: 18~30, 30~45, and 45~60 ages; by preparation method: centrifugation and siphonage. The contents of fibrinogen (FIB) and factor Ⅷ in cryoprecipitated antihemophilic factor in each group were compared. 【Results】 The content of FIB and factor Ⅷ in females were higher than those in males(P<0.05). The content of factor Ⅷ differed statically by blood groups (P<0.05), which was lower in group O than others [graup A(180.5±75.2)IU, graup B(155.1±59.4)IU, graup O(109.3±46.4)IU, graup AB(168.5±65.1)IU]. The content of factor Ⅷ increased with age statistically (P<0.05). The content of FIB prepared by centrifugation [(373.3±126.1)mg] was superior to siphonage [(309.4±85.6)mg] (P<0.05), while the content of factor Ⅷ prepared by siphonage [(172.4±71.3)IU] was superior to centrifugation [(124.0±49.1)mg] (P<0.05). 【Conclusion】 Gender and preparation method are the influencing factors of FIB. Gender, age, blood group and preparation method are the influencing factors of the content of factor Ⅷ. The FFP prepared by whole blood preserved with the ACD (citrate, sodium citrate and glucose) solution at any time within 8h after the collection has no impact on the quality of cryoprecipitated antihemophilic factor.

Objective: To investigate the histomorpholgic spectrum, immunophenotypic, and molecular genetic features of Sertoli cell tumor, not otherwise specified (SCT, NOS) of the testis. Methods: Seven cases of SCT, NOS of the testis were analyzed(4 from Peking University Third Hospital and 3 from Zhejiang Provincial People′s Hospital) between 2008 and 2017. The histopathologic features were examined based on HE staining, and EnVision method was used for immunohistochemistry staining of calretinin, inhibin, β-catenin, cyclinD1, CD10, CKpan, neuroendocrine markers, WT1, Melan A, vimentin, SALL4, GATA3, PAX8, and S-100 protein. Mutational analysis of exon 3 of the CTNNB1 gene by polymerase chain reaction (PCR)-amplified sequences and direct sequencing was performed. Results: Patients ages ranged from 22 to 65 years (mean 43 years). The clinical manifestation in all was a slowly enlarging, painless testicular mass.The maximum diameter of the tumor ranged from 1.5 cm to 3.0 cm (mean 2.1 cm). Sectioning usually disclosed a tan-gray to white mass with vague lobular cut-surface. Microscopically, the tumors were well circumscribed and non-encapsulated; the tumor cells were rearranged in multiple growth patterns from diffuse solid sheets to trabeculae and cords, ribbon and solid or hollow tubules setting in variable amount of acellular fibrous stroma. Two cases showed acellular collagenous stroma constituted >50% of the tumor confirming to the diagnosis of sclerosing SCT. One case demonstrated a prominent myxoid stromal change. The tumor cells typically had moderate amounts of pale to lightly eosinophilic cytoplasm, 2 tumors had variable cells with abundant lipid-rich cytoplasm, and 1 other tumor showed scattered aggregates of multinucleated tumor cells. The tumor cells were bland-appearing without any evidence of atypia, mitoses were noted in 2 tumors (both were 1/50 HPF), but necrosis was absent. Immunohistochemical staining results as follows: vimentin (diffuse, 7/7), CD10 (diffuse membrane, 7/7); diffuse β-catenin nuclear and cytoplasm staining in 5 of 7 cases, and all the 5 cases showed diffuse cyclin D1 nuclear staining, β-catenin membrane staining in 2 of 7 cases, CKpan (5/7, focal or diffuse), calretinin (focal, 5/6), inhibin (focal, 3/7), synaptophysin (focal, 2/6), CD56 (focal or diffuse, 4/5), WT1 (diffuse nuclear, 4/5), and S-100 protein (diffuse, 3/7), and chromogranin A, Melan A, PAX8, GATA3 and SALL4 all were negative. Molecular genetic studies of PCR and direct sequencing showed CTNNB1 mutations in 4 of 7 (4/7) cases, 4 of the four mutation-carrying cases showed diffuse β-catenin nuclear and cytoplasm immunoreactivity and diffuse cyclin D1 nuclear immunoreactivity in the tumor cells. Conclusions SCT, NOS of the testis typically shows significant heterogeneities in both morphology and immunohistochemistry, thus causing differential diagnostic confusions. Molecular analyses showed mutations of exon 3 of CTNNB1 in more than half of these tumors, and nuclear accumulation of β-catenin and over expression of cyclin D1 can be useful for the differential diagnosis of SCT, NOS.

Objective: To investigate the clinicopathologic and molecular genetic features of secretory carcinoma of salivary gland (SCSG). Methods: Six cases of SCSG were collected from Zhejiang Provincial People's Hospital from January 2011 to March 2018. The clinical, histopathological and immunohistochemical features were analyzed and fluorescence in situ hybridization (FISH) was used to detect ETV6 gene rearrangement. Results: Four out of 6 tumors originated in the parotid gland and one of each in the minor salivary glands of soft palate and the buccal mucosa. Grossly, 4 cases were solid and 2 were partially cystic with maximum diameter ranging from 1.0 to 4.0 cm. Microscopically, 5 tumors showed typical features of low grade SCSG with tumor divided by thin fibrous septa into lobules composed of solid acinar, microcystic, follicular and papillary structures with abundant extracellular mucinous secretions. The tumor cells had cuolated or hobnail cytoplasm with low-grade nuclei and scarce mitoses. Perineural invasion was present in 1 case. The remaining tumor showed about 30% of the tumor areas with high-grade transformation characterized by proliferation of a distinct population of anaplastic cells arranged in irregular glandular, small nested and single cell patterns that were surrounded by desmoplastic stroma and invaded into surface mucosa with ulceration. Immunohistochemistry showed that all 6 tumors had diffuse and strong reactivities to S100 protein and cytokeratin 7, and 4 cases showed focal reactivity to gross cystic disease fluid protein 15 (GCDFP15), all were negative for discovered on gist 1 (DOG1), cytokeratin 20, p63 and calponin. High grade transformation cases were analysed, the high grade SCSG components showed a significantly increased Ki-67 index and cyclin D1 positive tumor cells compared to the conventional SCSG components. FISH analyses showed that 4 cases had ETV6 gene rearrangement. Eleven to seventy one months' follow-up showed no evidence of tumor recurrence nor metastasis. Conclusions SCSG harbors characteristic genetic abnormalities with ETV6 gene rearrangement and typically shows a low grade morphology with occasionally, high grade transformation can be present.