OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

OBJECTIVE: To retrospectively analyze the clinical data of newly diagnosed acute myeloid leukemia (AML) patients treated with venetoclax combined with azacitidine (Ven/Aza) or standard "3+7" regimen and similar regimens, collect real-world study data, compare the treatment response and adverse events between the two regimens, as well as perform survival analysis. METHODS: To retrospectively analyze the efficacy, survival, and adverse reactions of newly diagnosed AML patients treated with Ven/Aza (24 cases) and "3+7" regimens (117 cases ) in our hospital from September 2009 to March 2023, as well as factors influencing outcomes. A propensity score matching (PSM) was performed on age and Eastern Cooperative Oncology Group performance status (ECOG PS) to obtain a 1:1 matched cohort of 20 pairs, and the efficacy and survival before and after the matching were compared. RESULTS: The median age of patients in the Ven/Aza group was 69 years, while that in the "3+7" group was 56 years (P <0.001). Objective remission rate (ORR) was 62.5% in Ven/Aza group and 74.8% in "3+7" group (P >0.05). The median overall survival (OS) in the Ven/Aza group was 522 days, while that in the "3+7" group was 1 002 days (P >0.05). After controlling the two variables of age and ECOG PS, a PSM cohort of 20 pairs was obtained, in which the ORR was 65% in Ven/Aza group and 60% in "3+7" group (P >0.05). The median OS was 522 days and 629 days, and median progression-free survival (PFS) was 531 days and 198 days between the two groups, respectively. There were no statistically significant differences in OS and PFS between the two groups (both P >0.05). Additionally, the incidence of adverse events in the Ven/Aza group was significantly reduced. CONCLUSION The overall cohort shows that the "3+7" regimen has advantages in efficacy and survival, but Ven/Aza regimen is relatively safer. After performing PSM on age and ECOG PS, the Ven/Aza group showed improved efficacy, and a longer median PFS compared to "3+7" group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Sulfonamides/administration & dosage* ; Azacitidine/administration & dosage* ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Aged ; Middle Aged ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

Objective To investigate the association of endometrial thickness(EMT)with obstetric and neonatal outcomes of monoparous pregnancy in fresh cleavage embryos transfer.Methods A total of 1 845 patients of monoparous pregnancy after fresh cleavage embryos transfer cycles from Jan 2016 to Mar 2022 at Shanghai First Maternity and Infant Hospital,Tongji Universtiy were analyzed retrospectively.Patients were categorized into three groups by EMT on transferation day:≤8 mm(group A),8-14 mm(group B)and≥14 mm(group C).The primary outcomes were preterm birth(PTB),birth weight and birth weight z-score,small-for-gestation age,large-for-gestation age,very low birth weight,low birth weight and macrosomia.The second outcomes were pregnancy and perinatal complications.The relationship between EMT and adverse neonatal outcomes was estimated by Logistic regression analysis.Results The rate of ectopic pregnancy was increased significantly in group A.No significant differences were found among the three groups in gestation age,birth weight,birth weight z-score,PTB,small for gestation age,large for gestation age,low birth weight,very low birth weight and macrosomia.Compared with group B,the odds of adverse neonatal outcomes did not show significant differences before and after adjustment in both group A and group C by Logistic regression analysis.Conclusion Thinner EMT in fresh cleavage embryos transfer is associated with higher rate of ectopic pregnancy,while it is not independently associated with adverse perinatal outcomes.

Objective To investigate the association of endometrial thickness(EMT)with obstetric and neonatal outcomes of monoparous pregnancy in fresh cleavage embryos transfer.Methods A total of 1 845 patients of monoparous pregnancy after fresh cleavage embryos transfer cycles from Jan 2016 to Mar 2022 at Shanghai First Maternity and Infant Hospital,Tongji Universtiy were analyzed retrospectively.Patients were categorized into three groups by EMT on transferation day:≤8 mm(group A),8-14 mm(group B)and≥14 mm(group C).The primary outcomes were preterm birth(PTB),birth weight and birth weight z-score,small-for-gestation age,large-for-gestation age,very low birth weight,low birth weight and macrosomia.The second outcomes were pregnancy and perinatal complications.The relationship between EMT and adverse neonatal outcomes was estimated by Logistic regression analysis.Results The rate of ectopic pregnancy was increased significantly in group A.No significant differences were found among the three groups in gestation age,birth weight,birth weight z-score,PTB,small for gestation age,large for gestation age,low birth weight,very low birth weight and macrosomia.Compared with group B,the odds of adverse neonatal outcomes did not show significant differences before and after adjustment in both group A and group C by Logistic regression analysis.Conclusion Thinner EMT in fresh cleavage embryos transfer is associated with higher rate of ectopic pregnancy,while it is not independently associated with adverse perinatal outcomes.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective To explore the mechanism by which paeoniflorin improves trabecular meshwork(TM)cell dysfunction.Methods C57BL/6J mice were randomly divided into the following groups:Control group(no treatment),model group(glaucoma model constructed by ocular perfusion)and paeoniflorin group(glaucoma model followed by treatment with 50 mg·kg-1 paeoniflorin).Each group consisted of 12 mice.After 14 days of treatment,intraocular pressure was measured;and trabecular meshwork tissue was collected.TdT mediated dUDP nick end labeling(TUNEL)assay was performed to detect cell apoptosis.Western blot was used to measure protein expression levels.HTMC cells were randomly divided into the following groups:Normal group(cultured under standard conditions),rapamycin group(50 μmol·L-1 rapamycin as an autophagy inducer),experimental-L group(50 μmol·L-1 rapamycin+10 μmol·L-1 paeoniflorin)and experimental-H group(50 μmol·L-1 rapamycin+30μmol·L-1 paeoniflorin).Western blot was used to measure protein expression levels.Methyl thiazolyl tetrazolium(MTT)assay and flow cytometry were applied to evaluate cell proliferation and apoptosis.Results After 14 days of treatment,the intraocular pressure in the control,model and paeoniflorin groups were(12.81±0.83),(26.31±1.85)and(20.64±1.77)mmHg,respectively;the positive cell rate detected by the TUNEL assay were(4.86±0.44)％,(30.32±5.15)％and(15.08±1.92)％,respectively;the levels of microtubule associated protein 1 light chain 3(LC3)Ⅱ/LC3 Ⅰ protein were 0.51±0.06,1.33±0.13 and 0.72±0.08,respectively;Collagen Ⅰ protein levels were 0.45±0.07,1.11±0.12 and 0.72±0.05,respectively.The above indexes of the model group were statistically significant compared with the control group,and the above indexes of the paeoniflorin group were statistically significant compared with the model group(P＜0.001,P＜0.01).The LC3 Ⅱ/LC3 Ⅰ protein levels in the normal,rapamycin,experimental-L,experimental-H groups were 0.40±0.03,1.54±0.10,0.98±0.10 and 0.64±0.06,respectively;the cell viability rates were(100.00±6.25)％,(65.96±6.16)％,(75.22±5.54)％and(82.15±5.14)％,respectively;the apoptosis rates were(4.80±0.37)％,(19.64±0.97)％,(16.10±0.93)％and(13.16±0.94)％,respectively.The above indexes in the rapamycin group were significantly different from those in the normal group,and the above indexes in the experimental-L,-H groups were significantly different from those in the rapamycin group(P＜0.001,P＜0.05).Conclusion Paeoniflorin may improve trabecular meshwork cell dysfunction by regulating autophagy and reducing cell apoptosis,which may provide potential therapeutic strategies for glaucoma.

Objective:To explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma(SCNSL).Methods:Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected.A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival.Multivariate logistic regression analysis was used to explore the adverse prognostic factors.Results:Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research.Their 2-year overall survival(OS)rate was 46.01％and median survival time was 18.1 months.The 2-year OS rates of HD-MTX group and TMZ group were 34.3％and 61％,median survival time were 8.7 and 38.3 months,and median progression-free survival time were 8.1 and 47 months,respectively.Multivariate logistic regression analysis showed that age,sex,IPI,Ann Arbor stage were correlated with patient survival time.The median survival time of patients with CD79B,KMT2D,CXCR4.ERBB2,TBL1XR1,BTG2,MYC,MYD88,and PIM1 mutations was 8.2 months,which was lower than the overall level.Conclusion:HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis,and early application of gene sequencing is beneficial for evaluating prognosis.

Objective To explore the mechanism by which paeoniflorin improves trabecular meshwork(TM)cell dysfunction.Methods C57BL/6J mice were randomly divided into the following groups:Control group(no treatment),model group(glaucoma model constructed by ocular perfusion)and paeoniflorin group(glaucoma model followed by treatment with 50 mg·kg-1 paeoniflorin).Each group consisted of 12 mice.After 14 days of treatment,intraocular pressure was measured;and trabecular meshwork tissue was collected.TdT mediated dUDP nick end labeling(TUNEL)assay was performed to detect cell apoptosis.Western blot was used to measure protein expression levels.HTMC cells were randomly divided into the following groups:Normal group(cultured under standard conditions),rapamycin group(50 μmol·L-1 rapamycin as an autophagy inducer),experimental-L group(50 μmol·L-1 rapamycin+10 μmol·L-1 paeoniflorin)and experimental-H group(50 μmol·L-1 rapamycin+30μmol·L-1 paeoniflorin).Western blot was used to measure protein expression levels.Methyl thiazolyl tetrazolium(MTT)assay and flow cytometry were applied to evaluate cell proliferation and apoptosis.Results After 14 days of treatment,the intraocular pressure in the control,model and paeoniflorin groups were(12.81±0.83),(26.31±1.85)and(20.64±1.77)mmHg,respectively;the positive cell rate detected by the TUNEL assay were(4.86±0.44)％,(30.32±5.15)％and(15.08±1.92)％,respectively;the levels of microtubule associated protein 1 light chain 3(LC3)Ⅱ/LC3 Ⅰ protein were 0.51±0.06,1.33±0.13 and 0.72±0.08,respectively;Collagen Ⅰ protein levels were 0.45±0.07,1.11±0.12 and 0.72±0.05,respectively.The above indexes of the model group were statistically significant compared with the control group,and the above indexes of the paeoniflorin group were statistically significant compared with the model group(P＜0.001,P＜0.01).The LC3 Ⅱ/LC3 Ⅰ protein levels in the normal,rapamycin,experimental-L,experimental-H groups were 0.40±0.03,1.54±0.10,0.98±0.10 and 0.64±0.06,respectively;the cell viability rates were(100.00±6.25)％,(65.96±6.16)％,(75.22±5.54)％and(82.15±5.14)％,respectively;the apoptosis rates were(4.80±0.37)％,(19.64±0.97)％,(16.10±0.93)％and(13.16±0.94)％,respectively.The above indexes in the rapamycin group were significantly different from those in the normal group,and the above indexes in the experimental-L,-H groups were significantly different from those in the rapamycin group(P＜0.001,P＜0.05).Conclusion Paeoniflorin may improve trabecular meshwork cell dysfunction by regulating autophagy and reducing cell apoptosis,which may provide potential therapeutic strategies for glaucoma.

Objective: To evaluate the clinical value of new coagulation biomarkers including soluble thrombomodulin (sTM) and tissue plasminogen activator inhibitor complex (t-PAI·C) for the diagnosis and prognosis of sepsis in children. Methods: The prospective observational study enrolled 59 children who were diagnosed with sepsis including severe sepsis and septic shock in the Department of Pediatric Critical Care Medicine of Shanghai Children's Medical Center affiliated to the Medical College of Shanghai Jiao Tong University from June 2019 to June 2021. The sTM, t-PAI·C and conventional coagulation tests were detected on illness day one of sepsis. Twenty healthy children were selected as the control group, and the above parameters were detected on the day of inclusion. Children with sepsis were divided into survival group and non-survival group according to prognosis at discharge. Baseline comparisons between groups were performed using Mann-Whitney U test. Multivariate Logistic regression analysis was used to evaluate the risk factors for the diagnosis and prognosis of sepsis in children. Receiver operating characteristic (ROC) curve was conducted to evaluate the predictive values of above variables for the diagnosis and prognosis of sepsis in children. Results: The sepsis group included 59 patients (39 boys and 20 girls), aged 61(22, 136)months. There were 44 patients in the survival group and 15 patients in the non-survival group, respectively. The control group consisted of 20 boys, aged 107 (94,122) months. Patients in the sepsis group had higher sTM and t-PAI·C ((12 (9, 17)×10³ vs. 9(8, 10)×10³ TU/L, 10(6, 22) vs. 2 (1, 3) μg/L, Z=-2.15, -6.05, both P<0.05) compared with children in the control group. The t-PAI·C was superior to sTM for the diagnosis of sepsis. The areas under the curve (AUC) of t-PAI·C and sTM for the diagnosis of sepsis were 0.95 and 0.66, respectively, and the optimal cut-off value were 3 μg/L and 12×10³ TU/L, respectively. Patients in the survival group had lower sTM (10 (8, 14)×10³ vs. 17 (11, 36)×10³ TU/L, Z=-2.73, P=0.006) than those in the non-survival group. Logistic regression analysis showed that sTM was a risk factor for death at discharge (OR=1.14, 95%CI 1.04-1.27, P=0.006). The AUC of sTM and t-PAI·C for predicting death at discharge were 0.74 and 0.62, respectively, and the optimal cut-off values were 13×10³ TU/L and 6 μg/L, respectively. The AUC of sTM combined with platelet counts for predicting death at discharge was 0.89, which was superior to sTM and t-PAI·C. Conclusion: The sTM and t-PAI·C had clinical application values in diagnosing and predicting prognosis in pediatric sepsis.
Child ; Female ; Humans ; Male ; Biomarkers ; China ; Sepsis/diagnosis* ; Shock, Septic ; Tissue Plasminogen Activator ; Infant ; Child, Preschool