Bisphosphonate-related osteonecrosis of jaw(BRONJ)is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells(BMSCs).Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic disorders.However,the role of corin in BRONJ-related BMSCs dysfunction remains unclarified.A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic differentiation.Corin knockdown inhibits BMSCs osteogenic differentiation,whereas corin overexpression or soluble corin(sCorin)exerts a promotion effect.Furthermore,corin expression is negatively regulated by bisphosphonates(BPs).Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ability.Mechanistically,we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin stimulation.PD98059(a selective ERK inhibitor)blocks the corin-mediated promotion effect.With regard to the high methylation level of corin during osteogenic differentiation,we apply a non-selective m6A methylase inhibitor,Cycloleucine,which also blocks the corin-mediated promotion effect.Furthermore,we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function,indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation ability.To conclude,our study reveals that corin reverses BPs-induced BMSCs dysfunction,and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK pathway.We hope this brings new insights into future clinical treatments for BRONJ.

Objective:To investigate the efficacy and prognosis of CLAG±DAC (Clofarabine, Cytarabine, G-CSF±Decitabine) chemotherapy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) .Methods:Continuous cases of R/R AML treated with the CLAG+DAC protocol or CLAG alone at the First Affiliated Hospital of Soochow University from January 2017 to December 2021 were retrospectively analyzed. The baseline characteristics, individual treatment regimen, treatment effect, disease progression, and survival status of patients were recorded. The factors influencing the efficacy of the CLAG±DAC chemotherapy regimens were analyzed, and the overall survival (OS) time after reinduction was calculated using the Kaplan-Meier method.Results:This study included a total of 53 patients, with 33 male patients and an average age of 40.6 years. Thirty-three patients achieved complete remission (CR+CRi) of the disease after the CLAG±DAC chemotherapy regimen and six patients achieved partial remission (PR), while 14 did not. Thirty-two patients eventually underwent hematopoietic stem cell transplantation, and the median OS of the patients was 55.9 months until follow-up. Patients with disease remission after the application of the CLAG±DAC chemotherapy had a significantly longer survival time than those without remission ( P<0.001). The results of the multifactorial analysis have revealed that combined DAC ( OR=4.60, 95% CI 1.14-23.5, P=0.04) and DNMT3A mutation ( OR=0.14, 95% CI 0.01-0.89, P=0.05) were the factors influencing the efficacy of the CLAG±DAC chemotherapy regimen. The remission rate was relatively higher in patients with R/R AML combined with FLT3-ITD mutation by applying the DAC+CLAG regimen ( OR=10.84, 95% CI 1.48-288.50, P=0.04) . Conclusion:The CLAG±DAC regimen is considered effective in patients with R/R AML, whereas decitabine combined with the CLAG regimen is more suitable for patients with R/R AML combined with FLT3-ITD mutation.

Objective:To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT.Methods:Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results:The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions:The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

Objective:To correlate neoadjuvant radiotherapy and chemotherapy efficacy with changes in peripheral blood T lymphocytes in patients with advanced mid-to-low rectal cancer.Methods:A total of 106 patients with rectal cancer who received treatment in Jinhua Municipal Central Hospital from January 2019 to December 2020 were included in this study. Fasting venous blood was taken before neoadjuvant radiotherapy and chemotherapy and 7 days before surgery to measure the numbers of CD3 +, CD4 +, CD8 +, CD45RA + and CD45RO + cells using flow cytometry. The optimal cut-off point was determined using the receiver operating curve. The influential factors of tumor regression grade were analyzed using logistic regression analysis. Results:After neoadjuvant radiotherapy and chemotherapy, the numbers of CD3 +, CD4 +, CD8 + cells were (401.86 ± 138.65), (225.83 ± 87.17), and (155.84 ± 71.19) respectively, which were significantly decreased compared with before neoadjuvant radiotherapy and chemotherapy [(477.33 ± 141.74), (647.38 ± 203.19), (348.22 ± 113.75), t = 10.78, 11.17, 9.49, all P < 0.05]. There were no significant differences in the percentages of CD3 +, CD4 +, CD8 +, CD45RA + and CD45RO + cells between before and after treatment (all P > 0.05). The percentage of CD45RO + cells was significantly increased after neoadjuvant radiotherapy and chemotherapy. A higher percentage of CD45RO + cells led to a lower tumor regression grade ( P < 0.05). The receiver operating characteristic curve showed that the optimal cut-off point of the percentage of CD45RO + cells was 1.08. The area under the receiver operating characteristic curve was 0.774 ( P = 0.029), with a sensitivity of 82.5% and specificity of 69.6%. The logistic regression analysis revealed that the percentage of CD45RO + cells was significantly correlated with tumor regression grade ( P < 0.05). Conclusion:The percentage of CD45RO + cells in T lymphocyte subsets before and after neoadjuvant radiotherapy and chemotherapy is closely related to tumor regression grade. It can be used as an indicator to predict the sensitivity of neoadjuvant radiotherapy and chemotherapy. This study is of great innovation and science and provides a new idea for clinical practice.

Objective:To investigate the survival and prognosis of B-lineage acute lymphoblastic leukemia (B-ALL) patients with TP53 mutation.Methods:The clinical data of 479 newly diagnosed B-ALL patients treated in the First Affiliated Hospital of Soochow University from January 2016 to December 2019 were retrospectively analyzed.Results:Among 479 B-ALL patients, 34 cases (7.1%) were positive for TP53 gene mutation, and a total of 36 TP53 mutations were detected, including 10 frameshift gene mutations (27.8%) , 23 missense mutations (63.9%) and 3 nonsense mutations (8.3%) . A total of 34 (94.4%) mutations were located in the DNA binding domain (exons 5-8) .The average number of mutated genes in patients with TP53 gene mutation (2.3) and the group without TP53 gene mutation (1.1) were statistically different ( P<0.001) . The proportion of Ph positive and Ph-like positive patients in the TP53 gene mutation negative group was significantly higher than that of the TP53 mutation positive group, and the difference was statistically significant ( P<0.001) . The 3-year OS and EFS rates of the TP53 gene mutation negative group were significantly higher than those of the TP53 gene mutation positive group. The differences in OS and EFS rates between the two groups were statistically significant ( χ2= 4.694, P = 0.030; χ2= 5.080, P= 0.024) . In the multivariate analysis, failure to achieve remission (CR) after one course of induction chemotherapy was an independent adverse prognostic factor affecting OS.Of the 34 patients with TP53 mutation, 16 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the CR 1 state, and 2 patients with recurrence after transplantation obtained CR 2 after infusion of donor-derived anti-CD19 chimeric antigen receptor T (CAR-T) cells. Among the 11 patients with TP53 gene mutation who relapsed during consolidation chemotherapy, 6 received anti-CD19 CAR T cell therapy, 4 patients achieved remission and minimal residual disease (MRD) turned negative, followed by bridging allo-HSCT, and 2 of them sustained CR. Conclusion:Missense mutations are the most common in B-ALL patients with TP53 gene mutation, and the majority of mutations were located in the DNA binding domain. B-ALL patients with TP53 gene mutation should undergo allo-HSCT as soon as possible after CAR-T cell therapy has cleared the MRD after recurrence. B-ALL patients with TP53 gene mutation still have a higher recurrence rate after allo-HSCT, and the infusion of donor-derived CAR-T cells can achieve better sustained remission.

Objective:To analyze the clinical characteristics of patients with different types of coronavirus disease 2019 (COVID-19).Methods:A total of 272 eligible COVID-19 patients who were admitted to Guangzhou Eighth People′s Hospital, Guangzhou Medical University from January 22 to February 15, 2020 were retrospectively enrolled. General characteristics, the first laboratory examination and imaging data of these patients were collected. According to the clinical classification, there were 236 cases in non-severe group (mild+ common type) and 36 cases in severe group (severe+ critical type). Comparisons between groups were performed by t test, chi-square test or rank-sum test when appropriate. Results:There were 23 males and 13 females in the severe group, 103 males and 133 females in the non-severe group, and the difference was statistically significant ( χ2=5.149, P=0.023). The age of severe group was (60.5±11.2) years, which was higher than that of non-severe group (46.8±15.7) years. The difference was statistically significant ( t=6.43, P<0.01). The lymphocyte (LYM) count, platelet (PLT) count and arterial partial pressure of oxygen (PaO 2) in the severe group were 0.90(0.55, 1.10)×10 9/L, 170.00(143.50, 198.00)×10 9/L and 73.50(69.70, 83.00) mmHg(1 mmHg=0.133 kPa), respectively, which were all lower than those in the non-severe group (1.42(1.09, 1.95)×10 9/L, 187.00(148.00, 230.00)×10 9/L and 96.00(83.20, 108.00) mmHg, respectively). The differences were all statistically significant ( Z=5.59, 2.00 and 5.00, respectively, all P<0.05). The levels of creatine kinase (CK), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), C reaction protein (CRP) and procalcitonin (PCT) in the severe group were 123.00(79.00, 212.00) U/L, 32.10(27.00, 47.40) U/L, 305.50(216.00, 396.00) U/L, 37.02(23.92, 63.66) mg/L and 0.09(0.05, 0.19) μg/L, respectively, which were all higher than those in the non-severe group (68.00(48.00, 103.00) U/L, 20.10(16.70, 26.20) U/L, 179.00(150.00, 222.00) U/L, 26.55(18.11, 36.96) mg/L and 0.04(0.03, 0.06) μg/L respectively), and the differences were all statistically significant ( Z=3.89, 5.60, 5.12, 2.85 and 5.43, respectively, all P<0.01). No significant differences were observed in white blood cell count, creatine kinase isoenzyme and blood lactate between the two groups ( Z=1.53, 0.41 and 1.00, respectively, all P>0.05). Conclusion:Gender, age, LYM count, PLT count, PaO 2, CK, AST, LDH, CRP and PCT could be used to provide reference for clinical classification of COVID-19 patients.

Objective: To investigate herpesvirus infection in early stage of hematopoietic stem cell transplantation (HSCT) by multiplex polymerase chain reaction (PCR), and to explore the association between multiple herpesviruses infection and clinical characteristics in HSCT patients and its impact on post-transplant complications and prognosis. Methods: A total of 734 peripheral blood samples were collected from 90 patients undergoing HSCT in the Department of Hematology, the First Affiliated Hospital of Soochow University between February 2017 and August 2017. The peripheral blood specimens were obtained before and within 90 days after transplantation at different time points. Lab-Aid824 Nucleic Acid Extraction Mini Reagent was used to extract DNA and multiplex PCR assay was used to simultaneously detect 8 kinds of human herpesviruses from genomic DNA. The incidence of various herpesvirus infections, its correlation with clinical features and effects on post-transplant complications and prognosis were analyzed. Results: The median follow-up time was 192 (range: 35-308) days. Among the 90 patients before transplantation, the incidence of herpes virus infection was 35.6% (32/90), including 12.2% (11/90) with one herpes virus infection and 23.3% (21/90) with multiple viruses infection. The incidence of herpes virus infection after transplantation was 77.8% (70/90), including 20.0% (18/90) with one herpes virus infection and 57.8% (52/90) with multiple herpes virus infection. Among the 52 patients with multiple herpes viruses infection, 30 (57.7%) patients were infected by 2 kinds of viruses, 18 (34.6%) patients by 3 kinds of viruses and 4 (7.7%) patients by 4 kinds of viruses. There was a correlation between HHV-6 and HHV-7 herpesvirus infection (OR=13.880, Q=0.026). EBV infection was related to HHV-7 infection (OR=0.093, Q=0.044). The age of patients was correlated with the incidence of HHV-1 infection before transplantation. There were 24 patients in our study experienced clinical symptoms associated with viral infection. The main manifestations were hemorrhagic cystitis (HC), interstitial pneumonia, enteritis, viral encephalitis and fever of unknown origin. EBV infection was related to HLA incompatibility and the inconsistent of the ABO blood group and grade Ⅱ-Ⅳ aGVHD after transplantation. HLA incompatibility and the unrelated donor and grade Ⅱ-Ⅳ aGVHD were related to multiple viruses infection. Conclusion Multiple herpesviruses were common in patients undergoing HSCT, which were closely related to HLA mismatch, unrelated donor and grade Ⅱ-Ⅳ aGVHD.

Objective: To explore the efficacy and safety of chimeric antigen receptor T (CAR-T) cells in the treatment of central nervous system leukemia (CNSL). Methods: Two leukemia patients with CNSL were treated with CD19-CAR-T cells. The process and results of the entire treatment is reported and related literature review is conducted. Results: The patients were diagnosed as acute myeloid leukemia (AML)-M₂ with B lymphoid antigen expression and B cell acute lymphoblastic leukemia(B-ALL) by morphology and immunophenotype assay. The immunophenotype was consistent with the abnormal manifestations of AML-M₂ and B-ALL. Their clinical manifestations and laboratory tests met the diagnostic criteria of CNSL. The diagnosis was clear and the two patients were treated with CD19-CAR-T cell immunotherapy. Central nervous system symptoms were relieved. The imaging abnormalities of patient one has disappeared but cytokines release syndrome (CRS) occurred during the treatment. Cerebrospinal fluid of patient two was negative and no obvious CRS reaction was found. Conclusions CAR-T cell immunotherapy is likely to induce the remission of CNSL and improve the prognosis.

Objective To investigate the protective effects of Erqi Decoction(EQD; mainly composed of Radix Aristolochiae Kaempferi, Radix Rhizoma Seu Flos Cypripedii, Cortex Fraxini, Cortex Phellodendri, Radix et Rhizoma Rhei) on the intestinal tract in rats with acute radiation intestinal injury and its mechanism. Methods Sixty SD rats were randomly divided into normal group, model group, EQD group and Baitouweng Decoction group (BD group), 15 rats in each group. The acute radiation enteritis model was established by exposing the whole abdomen to a total dose of 10 Gy of 6 MV higher-energy X-rays. EQD group and BD group were given intragastrical administration with corresponding medicine of EQD at the dose of 8.85 g·kg-1·d-1, BD at the dose of 4.69 g·kg-1·d-1 respectively, and the normal group and the model group were given intragastrical administration with the same volume of normal saline. The treatment lasted for 7 continuous days. After modeling, the morphological change of the proximal ileum tissue was observed under light microscope. Villus height, crypt depth, and thickness of the ileal mucosa and entire wall were measured by image analysis system. The myeloperoxidase (MPO) content in ileum tissue was determined by spectrophotometer, and the expression levels of caspase -3 and proliferating cell nuclear antigen (PCNA) in ileum tissue were determined by immunohistochemistry. Results EQD group and BD group had milder injuries of the ileal structure, and had higher villus height, crypt depth, and thickness of mucosa and entire wall than those in the model group (P <0.05), but there were no differences between the two medication groups(P > 0.05). MPO content in EQD group and BD group was decreased(P<0.05 compared with that in the model group), and MPO content in EQD group was lower than that in BD group. The expression levels of caspase-3 and PCNA were increased in EQD group and BD group(P < 0.05 compared with those in the model group), but there were no statistical differences between the two medication groups (P>0.05). Conclusion EQD has certain protective effects against radiation-induced intestinal damage, which mechanism is probably associated with relieving the local intestinal inflammatory reaction, accelerating intestinal epithelial cell proliferation, and inhibiting intestinal epithelial cell apoptosis.

Purpose To investigate the expression of EZH2 and p53 protein in breast cancer and to analyze their relationship with the clinical pathologic characteristics and prognosis. Methods The expression of EZH2 and p53 protein were detected by immunohisto-chemical method in 50 cases of breast adenosis tissues, 92 cases of breast invasive lobular carcinoma ( ILC) and 200 cases of breast in-vasive ductal carcinoma ( IDC) , and their correlation was also analyzed. Results There was no statistical significance of EZH2 be-tween ILC and IDC (P>0. 016 7), while its expression in breast adenosis tissues was lower than that in ILC and IDC (P<0. 016 7). In breast cancer the expression of EZH2 protein were not correlated with patient age, menopausal status, histological types, and pTNM stage. In contrast, its expression correlated with the tumor size, lymph node metastasis, molecular subtype, survival status and p53 (P<0. 05). There was no statistical significance of p53 between ILC and breast adenosis tissues (P>0. 016 7), while its expression in IDC was higher than that in ILC and breast adenosis tissues (P<0. 016 7). Its expression had no related to patient age, menopausal status, tumor size, lymph node metastasis in breast cancer, but related to histological types, pTNM stage, molecular subtype and sur-vival status (P<0. 05). The Kaplan-Meier survival analysis showed the expression of EZH2 and p53 had correlated with disease-free and overall survival rates of breast cancer (P<0. 05). Multivariate COX regression analysis showed that the expression of EZH2 and p53 were independent affecting factors to breast cancer patients. Conclusion The expression of EZH2 and p53 protein increase in the breast adenosis, ILC and IDC gradually, and they have positive correlation. The expression levels of EZH2 and p53 protein have im-portant value to evaluate the prognosis of breast cancer patients.