AIM:To investigate the effects of glutathione-S-transferase(GST)gene polymorphism on the concentration of 6-thioguanine nucleotides(6-TGN),an active metabolite of azathioprine(AZA),in patients with inflammatory bowel disease(IBD),in order to provide reference for the optimization of AZA treatment in patients.METHODS:The clini-cal data of patients with IBD treated by AZA were collected prospectively,the genotypes of GST-A1,GST-M1,GST-P1 and GST-T1 were detected by tar-geted sequencing of multiplex PCR combined with high-throughput sequencing technology before ad-ministration,and the steady-state trough concen-trations of 6-TGN in patients' red blood cells were determined by HPLC.Statistical analysis was carried out by SPSS 26.0 software.RESULTS:A total of 90 patients were included in this study.The alleles fre-quencies of GST-A1,GST-M1,GST-P1 and GST-T1 were consistent with Hardy-Weinberg equilibrium law.Logistic regression analysis showed that carry-ing GST-A1 mutant gene was an independent risk factor for the increase of trough concentration of 6-TGN(low concentration OR=17.50,P=0.030;high concentration OR=3.60,P=0.033),while the gene polymorphism of GST-M1,GST-P1,GST-T1 had no significant correlation with the concentration of 6-TGN(P＞0.05).CONCLUSION:The gene polymor-phism of GST-A1 may affect the concentration of 6-TGN,an active metabolite of AZA,and detection of GST-A1 genotype before AZA treatment will contrib-ute to clinical individualized medication.

AIM:To investigate the effects of glutathione-S-transferase(GST)gene polymorphism on the concentration of 6-thioguanine nucleotides(6-TGN),an active metabolite of azathioprine(AZA),in patients with inflammatory bowel disease(IBD),in order to provide reference for the optimization of AZA treatment in patients.METHODS:The clini-cal data of patients with IBD treated by AZA were collected prospectively,the genotypes of GST-A1,GST-M1,GST-P1 and GST-T1 were detected by tar-geted sequencing of multiplex PCR combined with high-throughput sequencing technology before ad-ministration,and the steady-state trough concen-trations of 6-TGN in patients' red blood cells were determined by HPLC.Statistical analysis was carried out by SPSS 26.0 software.RESULTS:A total of 90 patients were included in this study.The alleles fre-quencies of GST-A1,GST-M1,GST-P1 and GST-T1 were consistent with Hardy-Weinberg equilibrium law.Logistic regression analysis showed that carry-ing GST-A1 mutant gene was an independent risk factor for the increase of trough concentration of 6-TGN(low concentration OR=17.50,P=0.030;high concentration OR=3.60,P=0.033),while the gene polymorphism of GST-M1,GST-P1,GST-T1 had no significant correlation with the concentration of 6-TGN(P＞0.05).CONCLUSION:The gene polymor-phism of GST-A1 may affect the concentration of 6-TGN,an active metabolite of AZA,and detection of GST-A1 genotype before AZA treatment will contrib-ute to clinical individualized medication.

Objective:To investigate the clinicopathological features, immunophenotype and molecule characteristics of EWSR1::CREM fusion malignant epithelioid neoplasm in soft tissue.Methods:The clinical and pathological data of 2 cases of EWSR1::CREM fusion malignant epithelioid neoplasm in soft tissue diagnosed at the Department of Pathology, Beijing Jishuitan Hospital, Beijing, China from May 2023 to May 2024 were analyzed. Immunohistochemical study, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) were performed. Relevant literature was reviewed.Results:There were one male and one female patients, aged 35 and 29 years, respectively. The tumors developed in the somatic soft tissue, including calf and chest wall, and were 6.0 and 6.2 cm in size, respectively. The imaging studies suggested space-occupying lesions in muscle tissue. Case 1 did not involve the bone, while Case 2 showed fracture of the 8th rib. Microscopically, a fibrous pseudocapsule surrounded by lymphocytes and plasma cells was identified. The tumors were composed of small to medium-sized round and short spindle-shaped cells, showing nodular or sheet-like pattern. The tumor cells showed round nuclear outline, coarse chromatin with prominent nucleoli. Immunohistochemically, tumor cells showed diffuse positivity of ALK (D5F3), MUM1 and Syn, focal or patchy positivity of CKpan, EMA, S-100, NSE, WT-1 and SMA, and a high Ki-67 index (20%-30%). FISH demonstrated break-apart signals of EWSR1 gene in the 2 cases. NGS revealed EWSR1::CREM gene fusion. Case 2 showed an ATRX gene mutation. The two patients were free of recurrence or metastasis at the 10-month and 1-month follow-up, respectively.Conclusions:EWSR1::CREM fusion malignant epithelioid neoplasm is rare and lacks distinctive morphological and immunohistochemical features. FISH and NGS can help make a definitive diagnosis.

Objective:To investigate the clinicopathological and genetic characteristics of malignant transformation of polyostotic fibrous dysplasia (FD) in long bone.Methods:A retrospective analysis of clinical characteristics and morphological features was conducted from 4 cases of malignant transformation of FD diagnosed at Beijing Jishuitan Hospital from January 2016 to December 2023. Hotspot mutations for GNAS gene were tested in 4 cases by Sanger sequencing, in which both FD and malignant tissues were detected in 3 cases respectively.Results:There were 2 female and 2 male patients, aged 46 to 53 years [mean (49±3.2) years], and the course of the disease spanned from 2 months to 36 years. The tumor involved the femur ( n=2), tibia ( n=1) and humerus ( n=1). Three of them were diagnosed with FD before surgery. Single photon emission computed tomography showed multiple increases in bone metabolism, CT showed poorly margin, cortical destruction and soft tissue mass with uneven enhancement. Three cases had both FD and sarcoma components, while the remaining case exhibited exclusively sarcoma. The sarcomas displayed significant morphological variation, with 1 case diagnosed as osteosarcoma and 3 cases classified as low to high grade spindle cell sarcoma. Immunohistochemical results did not provide any indications for clear classification. Sanger sequencing demonstrated GNAS mutations of p.R201H (c.CGT>CAT, n=2) and p.R201C (c.CGT>TGT, n=2). All 4 cases were followed-up for 18 to 76 months, and received chemotherapy after surgery; 2 cases maintained disease-free, one case was diagnosed with invasive breast cancer through a core needle biopsy 3 months after chemotherapy, and another one was found to relapse 18 months after surgery. Conclusions:Some cases of polyostotic FD occur in association with café-au-lait macules and/or endocrine hyperfunctioning in McCune-Albright syndrome (MAS); polyostotic FD and MAS have more malignant potential than monostotic FD, but they are not the risk factors for FD malignancy. GNAS mutations may be involved in the occurrence and development of FD. The histologic types of malignant transformation of polyostotic FD in long bone are diverse, the sarcoma components of FD also present the GNAS mutation, suggesting potential involvement in the pathogenesis of FD malignancy.

Objective:To investigate the clinicopathological and genetic characteristics of malignant transformation of polyostotic fibrous dysplasia (FD) in long bone.Methods:A retrospective analysis of clinical characteristics and morphological features was conducted from 4 cases of malignant transformation of FD diagnosed at Beijing Jishuitan Hospital from January 2016 to December 2023. Hotspot mutations for GNAS gene were tested in 4 cases by Sanger sequencing, in which both FD and malignant tissues were detected in 3 cases respectively.Results:There were 2 female and 2 male patients, aged 46 to 53 years [mean (49±3.2) years], and the course of the disease spanned from 2 months to 36 years. The tumor involved the femur ( n=2), tibia ( n=1) and humerus ( n=1). Three of them were diagnosed with FD before surgery. Single photon emission computed tomography showed multiple increases in bone metabolism, CT showed poorly margin, cortical destruction and soft tissue mass with uneven enhancement. Three cases had both FD and sarcoma components, while the remaining case exhibited exclusively sarcoma. The sarcomas displayed significant morphological variation, with 1 case diagnosed as osteosarcoma and 3 cases classified as low to high grade spindle cell sarcoma. Immunohistochemical results did not provide any indications for clear classification. Sanger sequencing demonstrated GNAS mutations of p.R201H (c.CGT>CAT, n=2) and p.R201C (c.CGT>TGT, n=2). All 4 cases were followed-up for 18 to 76 months, and received chemotherapy after surgery; 2 cases maintained disease-free, one case was diagnosed with invasive breast cancer through a core needle biopsy 3 months after chemotherapy, and another one was found to relapse 18 months after surgery. Conclusions:Some cases of polyostotic FD occur in association with café-au-lait macules and/or endocrine hyperfunctioning in McCune-Albright syndrome (MAS); polyostotic FD and MAS have more malignant potential than monostotic FD, but they are not the risk factors for FD malignancy. GNAS mutations may be involved in the occurrence and development of FD. The histologic types of malignant transformation of polyostotic FD in long bone are diverse, the sarcoma components of FD also present the GNAS mutation, suggesting potential involvement in the pathogenesis of FD malignancy.

Objective:To investigate the clinicopathological features, immunophenotype and molecule characteristics of EWSR1::CREM fusion malignant epithelioid neoplasm in soft tissue.Methods:The clinical and pathological data of 2 cases of EWSR1::CREM fusion malignant epithelioid neoplasm in soft tissue diagnosed at the Department of Pathology, Beijing Jishuitan Hospital, Beijing, China from May 2023 to May 2024 were analyzed. Immunohistochemical study, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) were performed. Relevant literature was reviewed.Results:There were one male and one female patients, aged 35 and 29 years, respectively. The tumors developed in the somatic soft tissue, including calf and chest wall, and were 6.0 and 6.2 cm in size, respectively. The imaging studies suggested space-occupying lesions in muscle tissue. Case 1 did not involve the bone, while Case 2 showed fracture of the 8th rib. Microscopically, a fibrous pseudocapsule surrounded by lymphocytes and plasma cells was identified. The tumors were composed of small to medium-sized round and short spindle-shaped cells, showing nodular or sheet-like pattern. The tumor cells showed round nuclear outline, coarse chromatin with prominent nucleoli. Immunohistochemically, tumor cells showed diffuse positivity of ALK (D5F3), MUM1 and Syn, focal or patchy positivity of CKpan, EMA, S-100, NSE, WT-1 and SMA, and a high Ki-67 index (20%-30%). FISH demonstrated break-apart signals of EWSR1 gene in the 2 cases. NGS revealed EWSR1::CREM gene fusion. Case 2 showed an ATRX gene mutation. The two patients were free of recurrence or metastasis at the 10-month and 1-month follow-up, respectively.Conclusions:EWSR1::CREM fusion malignant epithelioid neoplasm is rare and lacks distinctive morphological and immunohistochemical features. FISH and NGS can help make a definitive diagnosis.

Objective:To investigate the diagnostic value of detecting MDM2 gene amplification by fluorescence in situ hybridization (FISH) in low-grade osteosarcoma (LGOS).Methods:Thirty cases of parosteal osteosarcoma (POS) and 14 cases of low-grade central osteosarcoma (LGCOS) from April 2009 to August 2022 at Beijing Jishuitan Hospital, Capital Medical University were analyzed for the presence of MDM2 gene amplification by FISH. Fifty-eight additional cases were used as negative controls (including 28 cases of fibrous dysplasia, 5 cases of giant cell tumor, 4 cases of conventional osteosarcoma, 2 cases each of periosteal osteosarcoma, reparative changes after fracture, pleomorphic undifferentiated sarcoma, low grade myofibroblastic sarcoma, fibrous dysplasia with malignant transformation, one case each of leiomyosarcoma, sclerosing epithelioid fibrosarcoma, malignant peripheral nerve sheath tumor, desmoplastic fibroma of bone, solitary fibrous tumor, aneurysmal bone cyst, clear cell chondrosarcoma, osteofibrous dysplasia, and 3 cases of unclassified spindle cell tumor).Results:Among the 30 patients with POS, 15 were male and 15 were female, ranging in age from 10 to 59 years (mean 35 years, median 30.5 years). Among the 14 patients with LGCOS, four were male and 10 were female, ranging in age from 15 to 56 years (mean 37 years, median 36 years). All except one case were successfully detected by FISH. MDM2 gene amplification was detected in 27 cases of POS (27/29,91.3%) and 8 cases of LGCOS (8/14). All the negative controls were negative for MDM2 gene amplification. The positive rate of MDM2 gene amplification was significantly different between the case group and the control group ( P<0.05). The sensitivity and specificity of MDM2 gene amplification in diagnosing POS and LGCOS were 91.3% and 100.0%; and 57.1% and 100.0%, respectively. The sensitivity and specificity of MDM2 gene amplification in diagnosing LGOS (including POS and LGCOS) were 81.3% and 100.0%, respectively. In cases where MDM2 gene was amplified, the MDM2 amplified signal was clustered. Nine cases showed increased CEP12 signal different from polyploidy which was displayed as small and weak signal points or cloud flocculent and cluster signals. Conclusions:Detection of MDM2 gene amplification by FISH is a highly sensitive and specific marker for LGOS. The interpretation criteria for FISH detection of MDM2 amplification are currently not unified. The signal characteristics need more attention when interpreting.

Objective:To investigate the clinicopathological and genetic characteristics of neuromuscular choristoma-associated desmoid type fibromatosis (NMC-DF).Methods:The clinical morphological and immunohistochemical features of 7 NMC-DF cases diagnosed from January 2013 to January 2023 in Beijing Jishuitan Hospital were retrospectively analyzed. A series of neuromuscular choristoma and neuromuscular choristoma-associated desmoid type fibromatosis were evaluated for CTNNB1 mutations, and hotspot mutations for CTNNB1 were tested in 4 NMC-DF cases using Sanger sequencing.Results:The tumors were collected from 3 females and 4 males, aged 1 to 22 years (mean 7.1 years), involving the sciatic nerve ( n=4), brachial plexus ( n=2) or multiple nerves ( n=1). The course of the disease spanned from 3 months to 10 years. Two cases were recurrent tumors. All the 7 NMC cases showed endoneurial intercalation of mature skeletal muscle fibers among the peripheral nerve fascicles, and the histologic features of the NMC-DF were strikingly similar to the conventional desmoid-type fibromatosis. By immunohistochemistry, all NMC and NMC-DF cases showed aberrant nuclear staining of β-catenin (7/7), the muscle cells in NMC were intensely immunoreactive for desmin, and the admixed nerve fibers were highlighted by NF and S-100 (7/7). Four NMC and NMC-DF had CTNNB1 mutations, 3 c.121A>G (p.T41A) and 1 c.134C>T (p.S45F). Follow-up of the 7 cases, ranging from 22 to 78 months, showed tumor recurrence in 2 patients at 3 and 8 months respectively after the first surgical resection, of which 1 patient underwent above-knee amputation. No recurrence occurred in other cases with tumor excision and neurological reconstruction surgery. There was no metastasis occurred in the 7 cases. Conclusions:NMC is a rare congenital lesion with differentiated mature skeletal muscle tissue found in peripheral nerve fascicles, and approximately 80% of patients with NMC develop a soft tissue fibromatosis. CTNNB1 mutation in the Wnt signaling pathway may be involved in the pathogenesis of NMC and NMC-DF, and S45F mutations seems to have a higher risk of disease progression.

Objective To analyze the current status and quality of existing obstetrics and gynecology enhanced recovery after surgery(ERAS)guidelines/consensus,understand the evidence-based practices in this field,and provide a basis for clinical decision-making.Methods A systematic search of PubMed,CNKI,and other databases,as well as NGC,SIGN,and websites of anesthesia societies domestically and internationally was conducted to obtain relevant guidelines and consensus on ERAS for gynecological surgery.The search was conducted from inception to July 1,2023,and the AGREE Ⅱ and RIGHT tools were used to analyze the current status and quality of the included guidelines/consensus,as well as to conduct a summary of the recommendations.Results A total of 5 guidelines and 10 consensus statements were included.The publication years were from 2018 to 2023,originating from the United States,China,Canada,and the United Kingdom.In the 6 areas evaluated using AGREEⅡ,clarity(66.06％)scored highest,followed by scope and purpose(56.67％),involvement of stakeholders(42.02％),and editorial independence(37.64％)with scores above 30％.The scores for rigor of development(26.88％)and applicability(4.17％)were relatively low.The same items among different evaluators indicated good consistency.The results of the scores in each area were as follows:A-level 2,B-level 13,and no C-level.Two high-quality guidelines were selected.The average RIGHT reporting rate was 44.38％.Subgroup analysis showed that guidelines were higher than consensus statements in the areas of rigor of development and applicability(P＜0.05),and that using GRADE was higher than not using(P＜0.05).The areas of rigor of development and clarity were higher in foreign guidelines than domestic guidelines(P＜0.05),and using evidence grading tools was higher than not using(P＜0.05).The summary of the recommendations showed that the quality of the evidence supporting the recommendations was uneven,and some recommendations were not specific enough.Conclusion The quality of the 15 included ERAS guidelines/consensus in obstetrics and gynecology is uneven,and 2 of them can be used as high-quality guidelines for clinical reference.The quality of evidence-based guidelines in foreign countries is higher,and the use rate of GRADE in foreign guidelines is high,most of which can provide clear recommendation strength and evidence level.Chinese guidelines/consensus are of lower quality compared to overseas,and methodology and report quality need further improvement.Overall,it is still necessary to strengthen the formulation of methods and reporting standards,improve the quality of evidence,and refine specific recommendations.

Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Arthroplasty, Replacement, Hip/adverse effects* ; Reoperation ; Prosthesis-Related Infections ; Retrospective Studies