Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective To investigate the correlation between serum cytotoxic T lymphocyte associated pro-tein 4(CTLA4),high mobility group box 1(HMGB1)and the balance of helper T cell 17(Th17)/regulatory T cell(Treg),and to study their diagnostic significance for unexplained recurrent spontaneous abortion(URSA).Methods A total of 102 patients with URSA admitted to the hospital from September 2022 to September 2024 were selected as the URSA group,and another 80 healthy pregnant women who underwent prenatal examinations in the hospital during the same period were selected as the healthy group.The levels of serum CTLA4 and HMGB1 in the two groups were detected,the levels of Th17 and Treg in the two groups were detected,the Th17/Treg ratio was calculated,and the general data of the two groups were collected and recorded.Pearson was used to analyze the correlations between the levels of serum CLTA4 and HMGB1 and Th17,Treg,and Th17/Treg.logistic regres-sion was used to analyze the influencing factors of URSA occurrence.The receiver operating characteristic(ROC)curve was used to analyze the value of serum CTLA4 and HMGB1 levels in evaluating the occurrence of URSA.Results the serum CTLA4 level in the URSA group was lower than that in the healthy group,the HMGB1 level was higher than that in the healthy group,the Th17 level and Th17/Treg were higher than those in the healthy group,and the Treg level was lower than that in the healthy group(P<0.05).The serum CTLA4 level was nega-tively correlated with the Th17 level and Th17/Treg,and positively correlated with the Treg level(P<0.05).The level of HMGB1 was positively correlated with the level of Th17 and Th17/Treg,and negatively correlated with the level of Treg(P<0.05).Pregnancy frequency,serum CTLA4 level,serum HMGB1 level,Th17 level,Treg level,and Th17/Treg are independent influencing factors for the occurrence of URSA(P<0.05).The areas under the curve(AUC)of serum CTLA4 and HMGB1 levels and the combined evaluation of URSA by the two indicators were 0.841,0.787,and 0.908 respectively,and the Youden indices were 0.652,0.491,and 0.656 respectively.Conclusions The serum CTLA4 level is decreased and the HMGB1 level is increased in patients with URSA,which is related to the change of Th17/Treg balance.The levels of serum CTLA4 and HMGB1 have auxiliary diag-nostic significance for URSA.

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.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective To investigate the correlation between serum cytotoxic T lymphocyte associated pro-tein 4(CTLA4),high mobility group box 1(HMGB1)and the balance of helper T cell 17(Th17)/regulatory T cell(Treg),and to study their diagnostic significance for unexplained recurrent spontaneous abortion(URSA).Methods A total of 102 patients with URSA admitted to the hospital from September 2022 to September 2024 were selected as the URSA group,and another 80 healthy pregnant women who underwent prenatal examinations in the hospital during the same period were selected as the healthy group.The levels of serum CTLA4 and HMGB1 in the two groups were detected,the levels of Th17 and Treg in the two groups were detected,the Th17/Treg ratio was calculated,and the general data of the two groups were collected and recorded.Pearson was used to analyze the correlations between the levels of serum CLTA4 and HMGB1 and Th17,Treg,and Th17/Treg.logistic regres-sion was used to analyze the influencing factors of URSA occurrence.The receiver operating characteristic(ROC)curve was used to analyze the value of serum CTLA4 and HMGB1 levels in evaluating the occurrence of URSA.Results the serum CTLA4 level in the URSA group was lower than that in the healthy group,the HMGB1 level was higher than that in the healthy group,the Th17 level and Th17/Treg were higher than those in the healthy group,and the Treg level was lower than that in the healthy group(P<0.05).The serum CTLA4 level was nega-tively correlated with the Th17 level and Th17/Treg,and positively correlated with the Treg level(P<0.05).The level of HMGB1 was positively correlated with the level of Th17 and Th17/Treg,and negatively correlated with the level of Treg(P<0.05).Pregnancy frequency,serum CTLA4 level,serum HMGB1 level,Th17 level,Treg level,and Th17/Treg are independent influencing factors for the occurrence of URSA(P<0.05).The areas under the curve(AUC)of serum CTLA4 and HMGB1 levels and the combined evaluation of URSA by the two indicators were 0.841,0.787,and 0.908 respectively,and the Youden indices were 0.652,0.491,and 0.656 respectively.Conclusions The serum CTLA4 level is decreased and the HMGB1 level is increased in patients with URSA,which is related to the change of Th17/Treg balance.The levels of serum CTLA4 and HMGB1 have auxiliary diag-nostic significance for URSA.

Humans ; Consanguinity ; Exome Sequencing ; Mutation/genetics* ; Sequence Analysis, DNA ; Ciliary Motility Disorders ; Axonemal Dyneins/genetics*

Objective To objectively classify cancer-related fatigue(CRF)patients with qi and blood deficiency syndrome;To explore possible enrichment characteristics;To provide ideas for precise population identification.Methods A cross-sectional study was conducted,611 CRF patients with qi and blood deficiency syndrome were included from October 2019 to April 2022.Clinical symptoms of patient were documented,including pale or withered-yellow complexion,shortness of breath with reluctance to talk,dizziness,spontaneous sweating,and palpitations.Additionally,blood routine were conducted,including white blood cell(WBC)count,red blood cell(RBC)count,hemoglobin(HGB),platelet(PLT)count,and neutrophil count(NEUT).The degree of fatigue was assessed using the Piper Fatigue Scale(PFS).Data analysis was performed using R 4.2.0.Clustering analysis was performed using the K-mediods method.Results Through unsupervised clustering analysis,the target population was divided into three categories:qi and blood deficiency syndrome leaning towards qi deficiency,qi and blood deficiency syndrome with mild symptom,qi and blood deficiency syndrome leaning towards blood deficiency.In terms of fatigue severity,the first two groups showed comparable levels,while the third group exhibited the most severe fatigue.Regarding objective indicators,the group leaning towards qi deficiency had the lowest WBC count,NEUT count and PLT count,and the group leaning towards blood deficiency had the lowest HGB count and RBC count.The group of qi and blood deficiency syndrome with mild symptom exhibited the highest level of objective indicators among the three.Conclusion By using clustering analysis methods,the study has preliminarily achieved population enrichment and classification based on syndromes,providing ideas for subsequent information enrichment and accurate identification of populations.Concurrently,the anemia index,WBC count and NEUT count demonstrate a inclination towards blood deficiency syndrome and qi deficiency syndrome,respectively.These findings indicate that these indicators could be incorporated into the syndrome diagnostic criteria for CRF to aid in the classification of the CRF population.

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.

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.