[Oligonucleotide drugs and their progress in stomatology].

Oligonucleotide drugs have the characteristics of targeting, modifiability and high biosafety. Recent studies have shown that oligonucleotide can be used to make biosensors, vaccine adjuvants, and has the functions of inhibiting alveolar bone resorption, promoting jaw and alveolar bone regeneration, anti-tumor, destroying plaque biofilm, and precise control of drug release. Therefore, it has a broad application prospect in the field of stomatology. This article reviews the classification, action mechanism and research status of oligonucleotide in stomatology. The aim is to provide ideas for further research and application of oligonucleotide.

[Oligonucleotide drugs and their progress in stomatology].

Oligonucleotide drugs have the characteristics of targeting, modifiability and high biosafety. Recent studies have shown that oligonucleotide can be used to make biosensors, vaccine adjuvants, and has the functions of inhibiting alveolar bone resorption, promoting jaw and alveolar bone regeneration, anti-tumor, destroying plaque biofilm, and precise control of drug release. Therefore, it has a broad application prospect in the field of stomatology. This article reviews the classification, action mechanism and research status of oligonucleotide in stomatology. The aim is to provide ideas for further research and application of oligonucleotide.

Tirofiban in the treatment of cancer-associated ischemic stroke.

OBJECTIVE: It is still unknown whether early tirofiban treatment improves prognosis in patients with cancer-related ischemic stroke without intravenous thrombolytic therapy. The purpose of this study was to assess the safety and efficacy of tirofiban in patients with cancer-associated ischemic stroke. PATIENTS AND METHODS: A retrospective analysis was performed on 75 patients with cancer and mild to moderate ischemic stroke, 34 of whom received tirofiban treatment and 41 aspirin treatment. The aspirin group received aspirin 100 mg QD, while the tirofiban group received continuous intravenous administration of tirofiban at a dosage of 0.1 µg/kg/min for 48 hours before switching to oral aspirin. RESULTS: The 24-hour and 7-day National Institute of Health Stroke Scale (NIHSS) scores for the tirofiban group were lower than those for the aspirin group (p=0.017 and p=0.035, respectively). The proportion of intracerebral hemorrhage occurring within 7 days did not differ significantly between the two groups (p>0.05), and neither did the 90-day Modified Rankin Scale (mRS) scores nor the incidence of ischemic stroke. CONCLUSIONS: Early administration of tirofiban in the treatment of mild to moderate ischemic stroke is safe, which can reduce 24-hour and 7-day NIHSS scores and has potential value.

PRC1 plays an important role in lung adenocarcinoma and is potentially targeted by fostamatinib.

OBJECTIVE: Lung adenocarcinoma (LUAD) is one of the most common cancers in the world. Protein regulator of cytokinesis 1 (PRC1) plays a role in the tumorigenesis and development of several cancers, including LUAD. The aim of the present study is to assess the characteristics of PRC1 in LUAD in order to find a potential drug that targets PRC1. MATERIALS AND METHODS: We investigated the prognostic value of PRC1 in patients with LUAD using Cox analysis of the RNA sequencing data from The Cancer Genome Atlas (TCGA) portal. A link between PRC1 and LUAD progression, cigarette smoking mutation count, aneuploidy, and hypoxia scores was assessed. The relationship between PRC1 and tumor-infiltrating immune cells in LUAD was analyzed and Gene Set Enrichment Analysis (GSEA) was used to study the PRC1-related biological process and signal pathways. Potential drugs targeting PRC1 were identified using DrugBank database and molecular docking. RESULTS: PRC1 expression was significantly increased in LUAD. PRC1 could be, therefore, a prognostic biomarker for predicting overall survival in LUAD. PRC1 expression was also related to cancer stage and patient's smoking history. PRC1 positively correlated with mutation count, aneuploidy and hypoxia scores. It was also significantly related to tumor-infiltrating immune cells, especially the activated mast cells. GSEA revealed that PRC1 might be correlated with cell cycle, cytokinesis and p53 signaling pathway. Additionally, fostamatinib was found to be a potential drug targeting PRC1. CONCLUSIONS: PRC1 may have a prognostic value for patients with LUAD, and be correlated with the mutation count, aneuploidy, hypoxia and tumor-infiltrating immune cells. Fostamatinib was found to be a potential drug targeting PRC1 in LUAD.

[Clinical application of laparoscopic sentinel lymph node mapping in early staged cervical cancer].

Objective: To investigate the application of sentinel lymph node biopsy (SLNB) in early-staged cervical cancer by laparoscopy. Methods: It was a prospective, single-arm, single-center clinical study. Seventy-eight cases of cervical cancer patients were collected from July 2015 to December 2018 at the Fourth Hospital of Hebei Medical University. All the patients were injected with tracer into the disease-free block of cervical tissue after anesthesia by the same surgeon who learned sentinel lymph node (SLN) mapping technique in Memorial Sloan-Kettering Cancer Center, and underwent SLN mapping followed by complete pelvic lymphadenectomy. Moreover, all the dissected lymph nodes were stained with hematoxylin eosin staining (HE) pathological examination. Besides, the negative SLN on hematoxylin-eosin staining were detected by immunohistochemistry cytokeratin staining micro-metastasis. To analyze the distribution, detection rate, false negative rate the sensitivity and negative predictive value of the SLN in early-staged cervical cancer by laparoscopy, and explore the value of SLN mapping in predicting the lymph nodes metastasis in early-staged cervical cancer. Results: The overall detection rate of SLN in cervical cancer was 99% (77/78), bilateral detection rate was 87% (68/78). The average of 12.4 lymph node (LN) and 3.6 SLN were dissected for each patients each side. SLN of cervical cancer were mainly distributed in the obturator space (61.5%, 343/558), followed by external iliac (23.5%, 131/558), common iliac (7.3%, 41/558), para-uterine (3.8%, 21/558), internal iliac (2.2%, 12/558), para abdominal aorta (1.1%, 6/558), and anterior sacral lymphatic drainage area (0.7%, 4/558). Fourteen cases of LN metastasis were found among all 78 cases. There were a total of 38 positive LN, including 26 SLN metastasis and 12 none sentinel LN metastasis. Through immunohistochemical staining and pathological ultra-staging, 1 SLN was found to be isolated tumor cells (ITC), and 5 SLNs were found to be micro-metastases (MIC), accounting for 23% (6/26) of positive SLN. SLN mapping with pathological ultra-staging improved the prediction of LN metastasis in cervical cancer (2/14). Metastatic SLN mainly distributed in the obturator space (65%, 17/26), peri-uterine region (12%, 3/26), common iliac region (15%, 4/26), and external iliac region (8%, 2/26). The consistency of the diagnosis of lymph node metastasis by SLN biopsy and postoperative retroperitoneal lymph node metastasis showed that the Kappa value was 1.000 (P<0.001), indicated that the metastasis status of SLN and retroperitoneal lymph node were completely consistent. The sensitivity, specificity, accuracy, false-negative rate, and negative predictive value of SLN biopsy in the diagnosis of lymph node metastasis were 100%, 100%, 100%, 0, and 100%, respectively. Conclusions: SLN in early-staged cervical cancer patients were mainly distributed in the obturator and external iliac space, pathalogical ultra-staging of SLN could improve the prediction of LN metastasis. Intraoperative SLN mapping is safe, feasible and could predict the state of retroperitoneal LN metastasis in early-staged cervical cancer. SLNB may replace systemic pelvic lymphadenectomy.

[Active surveillance for thyroid micro-malignant nodules].

Objective: To evaluate the effect of ultrasound diagnosis of thyroid micro-malignant nodules and accumulate practical experience for the management of active surveillance for them, so as to avoid overtreatment. Methods: A total of 949 patients who were diagnosed with thyroid malignant nodules using ultrasonography, with the nodules being less than 1 cm in size and without regional lymph node metastasis or distant metastasis, were included. They were treated by the same surgeon of the Department of Head and Neck Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from February 2014 to December 2020. 112 patients chose immediate surgery. The rest patients were asked to accept ultrasound examination every 6 months to 1 year. Follow-up endpoints: tumor size growth of 3 mm, tumor volume increase greater than 50%, lymph node metastasis or distant metastasis. Results: The median follow-up time was 19 months. 713 patients underwent surveillance for more than 6 months. Of the 713 patients, 570 (79.9%) were women, with mean age at 43.5 years old. Tumor progression was observed in 47 (6.6%) patients with a cumulative incidence of 2.7% (1 year), 7.2% (2 years) and 9.5% (3 years). In multivariate analysis, patient age [HR=0.508, 95%CI: 0.275-0.939, P=0.031], lesion number [HR=2.945, 95%CI: 1.593-5.444, P=0.001] and tumor size [HR=2.245, 95%CI: 1.202-4.192, P=0.011] at the beginning of observation were independent risk factors for tumor progression in patients with minimal thyroid malignant nodules during follow-up. During a median (range) active surveillance of 19 (6-80) months, 74 patients chose surgery during the surveillance. Among the 186 patients who underwent surgery, only 3 patients were diagnosed with fibrotic nodules in pathology, while the rest were papillary thyroid carcinoma. The ultrasound accuracy reached 98.4%(183/186). Conclusions: Ultrasonography is an effective method of diagnosing malignant thyroid nodules. Thyroid micro-malignant nodules progress slowly. As a result, it is safe to observe them instead of taking immediate surgery. Patient age, lesion number and tumor size at the beginning of observation are independent risk factors for the tumor progression of malignant nodules.

[Screening and analysis of prognostic factors of repairing single missing tooth by autotransplantation of teeth].

Objective: To screen and analyze the factors affecting the prognosis of replacing single missing tooth by autograft tooth, so as to provide reference for clinical judgment of surgical prognosis. Methods: A total of 176 patients (188 teeth) underwent autotransplantation of teeth in the Department of Oral & Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University from January 2017 to December 2019, including 85 teeth of males and 103 teeth of females were involved. The age was (33.0±9.8) years (16-65 years). The possible factors affecting the prognosis of replacing single missing tooth by autograft tooth were summarized and grouped, and the clinical and imaging data were recorded and judged. The surgical records and photographic data from the patients' previous medical records were retrospectively analyzed. The survival analysis method was used for statistical analysis to screen out the factors affecting the cumulative survival rate of transplanted teeth. Results: The 5-year cumulative survival rate of 188 transplanted teeth was 88.4%. Univariate Log-Rank analysis showed that age (P<0.001), sex (P=0.008), smoking (P<0.001), position of recipient area (P<0.001), height of alveolar bone in recipient area (P<0.001), time of donor tooth in vitro (P<0.001), use of donor model (P<0.001) and initial stability (P<0.001) were significantly correlated with cumulative survival rate of transplanted teeth. Multivariate Cox proportional hazard regression analysis showed that smoking (ß=-2.812, P=0.049), alveolar bone height (ß=1.521, P=0.020), donor time (ß=-2.001, P=0.019), use of donor model (ß=1.666, P=0.034) and initial stability (ß=-1.417, P=0.033) were significantly correlated with the cumulative survival rate of transplanted teeth. Conclusions: The prognosis of autogenous tooth transplantation can be predicted by smoking, height of alveolar bone in recipient area, time of donor teeth in vitro, use of donor model and initial stability. Good prognosis of transplanted teeth can be obtained by using donor model during operation, reducing the time of donor teeth in vitro, taking effective methods to restore alveolar bone height, maintaining good initial stability, and good oral health education after operation.

[Establishment of model to predict lateral neck recurrence of central lymph node metastasis in papillary thyroid carcinoma].

Objective: To explore the risk factors for lateral neck recurrence of central lymph node metastasis (CLMN) in papillary thyroid cancer (PTC), and to construct a model to predict the recurrence. Methods: The records of 245 consecutive PTC patients with CLMN underwent surgical treatment from 1996 to 2009 in our department were retrospectively reviewed. The threshold value of CLNM number is determined by ROC curve. The risk factors for lateral neck recurrence were determined by using Cox regression model. The identified risk factors were incorporated into a nomogram model to predict the risk of lateral neck recurrence. Results: A total of 245 patients were enrolled in the study, among them, 32 cases occurred lateral neck lymph node recurrence and 4 cases were dead of thyroid carcinoma. Multivariate analysis revealed that primary tumor size, extrathyroidal extension, the number of metastatic CLNM >3 were independent risk factors of lateral neck recurrence (P<0.05), lateral neck recurrence was a risk factor of disease-free survival(P<0.05). The nomogram model of predicting the lateral neck recurrence was further established based on the above 3 independent risk factors, the area under the receiver operating characteristic (ROC) curve of which was 0.790. Conclusions: The nomogram model based on the independent risk factors of LN recurrence can be helpful to screen the papillary thyroid carcinoma patients with high risk of lateral neck recurrence, and provide more guidance for clinical treatment.

Insulin-Like Growth Factor Binding Protein 5: an Important Regulator of Early Osteogenic Differentiation of hMSCs.

Insulin-like growth factor binding protein 5 (IGFBP5) is broadly bioactive, but its role in osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) remains to be clarified. Here, we demonstrated that IGFBP5 expression was markedly increased during the early osteogenic differentiation of hMSCs. We then over-expressed and knocked down this gene in hMSCs and evaluated the impact of manipulation of IGFBP5 expression on osteogenic differentiation based upon functional assays, ALP staining, and expression of osteogenic markers. Together, these analyses revealed that IGFBP5 over-expression enhanced early osteogenic differentiation, as evidenced by increased ALP staining and osteogenic marker induction, whereas knocking down this gene impaired the osteogenic process. Over-expression of IGFBP5 also markedly bolstered the extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation level, while IGFBP5 knockdown suppressed this signalling activity. We additionally compared the impact of simultaneous IGFBP5 overexpression and ERK1/2 inhibitor treatment to the effect of IGFBP5 over-expression alone in these hMSCs, revealing that small molecule-mediated EKR1/2 inhibition was sufficient to impair osteogenic differentiation in the context of elevated IGFBP5 levels. These findings indicated that IGFBP5 drives the early osteogenic differentiation of hMSCs via the ERK1/2 signalling pathway. Our results offer value as a foundation for future efforts to study and treat serious bone-related diseases including osteoporosis.

[Comparison of quality of life of hypopharyngeal squamous cell carcinoma patients after laryngeal preservation surgery and total laryngectomy].

Objective: To evaluate and compare the quality of life (QOL) in patients with hypopharyngeal squamous cell carcinoma after laryngeal preservation surgery and total laryngectomy. Methods: We selected parts of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the Head and Neck Module (EORTC QLQ-C30 and EORTC QLQ-H&N35) and designed the QOL questionnaire. We investigated 42 patients with hypopharyngeal squamous cell carcinoma underwent laryngeal preservation surgery and 38 patients underwent total laryngectomy by QOL questionnaire and followed up their survival. Results: The somatic function dimension, psychological function dimension, and social function dimension of patients underwent laryngeal preservation surgery were (92.46±15.71), (80.56±22.67) and (90.08±19.50), respectively, which were higher than (79.39±32.75), (68.42±25.05) and (61.84±29.55) of the total laryngectomy group (P<0.05), while the economic dimension was not significantly different between the two groups (P>0.05). The social function dimension (including social support and socialization, family relationship) of laryngeal preservation surgery group were (89.04±25.47) for postoperative time < 70 months and (90.94±13.28) for postoperative time ≥70 months, which were higher than (65.48±29.14) and (57.35±30.32) of the total laryngectomy group (P<0.01). Conclusions: The somatic function dimension, psychological function and social function of patients with hypopharyngeal squamous cell carcinoma underwent laryngeal preservation surgery obtain a better QOL than patients underwent total laryngectomy. Therefore, we should improve the laryngeal function and QOL of patients under the premise of ensuring the survival rate.

[Study of methylation of mitochondrial MT-COI of benzene poisoning].

Objective: To research the mitochondrial cytochrome c oxidase subunit I (MT-COI) gene methylation levels in patients with occupational chronic benzene poisoning, and to explore effective molec µlar biomarkers in patients with occupational chronic benzene poisoning. Methods: 38 confirmed cases of occupational chronic benzene poisoning were selected in the case group. 46 healthy people who underwent physical in our hospital were selected in the control group. Pyrosequencing was used to detect the methylation sites of methylation sites, flow cytometry was used to detect peripheral blood cell count levels, and non-parametric statistical methods were used to analyze the differences in detection results between the two groups. Results: The methylation level of mitochondrial MT-COI site 1 (2.21±0.81) % in the case group was less than that in the control group, and the difference was statistically significant (P<0.05) . The methylation level of mitochondrial MT-COI site 2 (2.31±0.96%) in the case group was less than that in the control group, and the difference was statistically significant (P<0.05) . The methylation average level of mitochondrial MT-COI (2.26±0.75) % in the case group was less than that in the control group, and the difference was statistically significant (P<0.05) . Analysis of the average level of methylation found that the methylation level of mitochondrial MT-COI was correlated with WBC (P<0.05) . Analysis of the average level of methylation found that the methylation level of mitochondrial MT-COI was correlated with platelets (r=0.254、0.280, P<0.05) . Conclusion: The level of mitochondrial MT-COI gene methylation in patients with occupational chronic benzene poisoning may be related to the sensitivity to benzene exposure. Mitochondrial MT-COI gene methylation may serve as a potential predictive biomarker for benzene poisoning.

[Potential risk factors predicting perioperative mortality in patients with gastric pull-up reconstruction].

Objective: To investigate the potential risk factors for the death of patients underwent gastric pull-up reconstruction following total pharyngoesophagectomy during perioperative periods. Methods: A total of 71 patients, including 64 males and 7 females, aged from 35 to 72 years old, with hypopharyngeal or cervical esophageal carcinoma, who underwent gastric pull-up reconstruction after pharyngoesophagectomy between October 2008 and October 2017, were reviewed retrospectively. Seventeen factors which may have potential influence on the mortality of patients during perioperative periods were evaluated by single factor Logistic regression analysis, and then those factors with obvious difference in statistics were further analyzed by multi-factor Logistic regression. Results: The rate of perioperative mortality was 9.9% (7/71). Single factor Logistic regression analysis indicated that the age of patients, abnormal electrocardiogram, TNM stages, alanine aminotransferase and D-Dimer changes, postoperative bleeding were risk factors for the death of patients(P values were 0.023, 0.004, 0.026, 0.021, 0.015 and 0.002, respectively). Multi-factor Logistic regression showed that postoperative bleeding and D-Dimer changes were 2 independent risk factors for perioperative death(P=0.021 and 0.047, respectively). Conclusions: Many potential factors may affect the perioperative mortality of patients underwent gastric pull-up reconstruction following total pharyngoesophagectomy. Postoperative bleeding and significantly elevated D-Dimer level were independent risk factors for the death of patients, indicating poor prognosis.

[Long-term outcome of patients with pyriform sinus squamous cell carcinoma treated with planned preoperative (chemo-) radiotherapy plus laryngeal function sparing surgery].

Objective: To analyze the long-term outcome of patients with pyriform sinus squamous cell carcinoma treated with planned preoperative (chemo-) radiotherapy plus laryngeal function sparing surgery. Methods: Patients with stage Ⅲ/Ⅳ pyriform sinus squamous cell carcinoma treated with planned preoperative (chemo-) radiotherapy plus laryngeal function sparing surgery during 1999 to 2000 were retrospectively analyzed. Data including concurrent chemotherapy or not, postoperative pathological diagnosis, postoperative complications, recurrence and survival were collected. Twenty patients were treated with preoperative radiotherapy while 14 patients with preoperative chemo-radiotherapy. Results: Among 31 cases of postoperative pathological diagnosed as pyriform sinus, 12 (38.7%) cases without tumor residue, 7 (22.5%) cases with severe radiation response and 12 (38.7%) cases with tumor residue. The 5-year cumulative local recurrence rate, regional recurrence rate and distant metastasis rate was 14.5%, 13.7% and 23.5%, respectively. Five-year cumulative overall survival rate and recurrence-free survival rate were 69.6% and 65.4%, respectively. Nine deaths were attributed to distant metastasis (8 cases) and regional recurrence (1 case). Conclusion: Most patients with pyriform sinus squamous cell carcinoma acquire long-term survival after treated with planned preoperative (chemo-) radiotherapy plus laryngeal function sparing surgery, and distant metastasis is the main cause of death.

Curcumin inhibits hypoxia inducible factor-1α-induced inflammation and apoptosis in macrophages through an ERK dependent pathway.

OBJECTIVE: Atherosclerosis, a kind of peripheral arterial disease with chronic inflammation, leads to the dysfunction of the vascular system and many other diseases. Hypoxia has been proven to participate in the progression of atherosclerosis, while curcumin can inhibit hypoxia-inducible factor 1α (HIF-1α). However, the underlying mechanisms are still elusive. PATIENTS AND METHODS: qRT-PCR was used to examine the expression of HIF-1α, IL-6 and TNFα of macrophages under hypoxic condition. Western blot was applied to examine the changes of HIF-1α, ERK and p-ERK after treatment with curcumin. Oli Red O staining and enzymatic assay were used to examine the lipid and total cholesterol in macrophages, respectively. ELISA was used to examine the release of IL-6 and TNFα by macrophages. FACS and MTT assays were applied to examine the apoptosis and proliferation of macrophages. RESULTS: Here, we found curcumin inhibited the expression of HIF-1α at the protein level in macrophages under hypoxic condition and curcumin and HIF-1α inhibitors repressed the total cholesterol and lipid level in macrophage under hypoxic condition. Moreover, curcumin also decreased the expression of HIF-1α downstream genes, VEGF, HMOX1, ROS and PDGF. Then, the data show the HIF-1α-induced apoptosis and inflammation of macrophages were inhibited by curcumin. Curcumin also rescued the proliferation defect of macrophages caused by hypoxia. Furthermore, we found it inhibited the expression of HIF-1α via ERK signaling pathway. CONCLUSIONS: We describe that curcumin inhibited the HIF-1α-induced apoptosis and inflammation of macrophages via ERK signaling pathways. These results suggest curcumin can be used for the treatment of atherosclerosis.

[Preliminary application of endonasopharyngeal ultrasound-guided transnasopharyngeal needle aspiration in the diagnosis of submucosal nasopharyngeal carcinoma].

Objective: To evaluate the feasibility, safety and clinical value of endonasopharyngeal ultrasound-guided transnasopharyngeal needle aspiration (ENUS-TNNA) in the diagnosis of submucosal nasopharyngeal carcinoma. Methods: Clinical data of 9 patients from Sichuan Cancer Hospital with submucosal nasopharyngeal carcinoma undergoing ENUS-TNNA between December 2013 and January 2018 were retrospectively analyzed. The feasibility and safety were analyed. All 9 patients were all males with a mean age of (49.2±10.9) years. Results: Needle puncture biopsies were successfully performed in all cases, and sufficient tissue sample for histopathological examination was obtained from each of the 9 patients. No major bleeding or persistent bleeding occurred during and after puncture procedures. There were 5 patients with undifferentiated nonkeratinizing carcinoma and 4 patients poorly differentiated carcinoma. Conclusion: ENUS-TNNA is a safe, feasible and effective technique to provide a diagnosis of submucosal growth type of nasopharyngeal neoplasms, which has some clinical value.

Gastric Stump Cancer Following Gastrectomy After Renal Transplantation: A Case Report.

A patient who had previously undergone a gastrectomy due to gastric ulcer perforation was admitted to our hospital. He presented with epigastric pain and poor oral intake accompanied with gastrointestinal bleeding, and was diagnosed with gastric stump cancer. He had a history of renal transplantation and was administered immunosuppressive agents. To alleviate the obstructive symptom and cure the gastrointestinal bleeding, the patient underwent surgical resection of the malignant tumor, with stable kidney function during the perioperative period. To the best of our knowledge, this is the first case reported in the English literature concerning gastric stump cancer that developed after renal transplantation. We speculate that the long-term use of immunosuppressants concomitant with gastrointestinal disorders after gastric surgery was an important causative factor in its etiology. We also investigated the possible treatment for it.

[Clinical analysis of autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation in thalassemia major].

Objective: To explore the diagnosis, treatment and prognosis of autoimmune hemolytic anemia (AIHA) after allo-HSCT in patients with thalassemia major (TM). Methods: A retrospective analysis of AIHA status after allo-HSCT in 291 TM patients from July 2007 to December 2017 was conducted. Results: Five of the 291 TM patients (1.72%) were diagnosed with post-transplant AIHA. The median time of AIHA was 7 (5-12) months after HSCT. All post-transplant AIHA patients were positive in direct and indirect Coombs test, the main clinical manifestations were dizziness, fatigue, pale complexion, skin and sclera yellow, and soy sauce urine. The incidence of AIHA was higher after unrelated donor transplantation (6.36%, 4/63) compared with that of sibling donor transplantation (0.43%, 1/228). One patient who received only prednison was dead. Four patients who received rituximab combined with prednisolone were alive, Coombs test in two of them were negative. Conclusions: AIHA after allo-HSCT developed in 1.72% patients with TM. Monitoring of Coombs test was important for diagnosis of post-transplant AIHA. The incidence of post-transplant AIHA was higher in unrelated donors compared with that of sibling donors transplantation. Treatment of rituximab combined glucocorticoid was effective strategy for post-transplant AIHA.

[The impact of genetic variation of KDR on clinical outcomes of advanced colorectal cancer patients treated by first line bevacizumab based regimens].

Objective: To investigate the association between kinase insertion region receptor (KDR) gene genetic variation and the efficacy of bevacizumab in patients with advanced colorectal cancer(CRC) were investigated in this study. Methods: 118 patients with advanced colorectal cancer who were treated by bevacizumab based first line regimens were included in this study. Peripheral blood and the biopsy tissue specimens of the CRC patients were collected for the genotyping of genetic variation and KDR gene expression, respectively. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate were adjusted by Cox regression analysis. Results: Located in the coding region, the prevalence of 889 C>T in KDR among the study population were as follows: CC genotype 86 cases (72.88%), CT genotype 30 cases (25.42%), TT genotype 2 cases (1.70%), minor allele frequency of 889 C>T is 0.14. The distribution of three genotypes in accordance with Hardy-Weinberg Equilibrium (P=0.737). There were no statistical differences in the distribution of the genotypes in baseline clinical data. TT and CT genotype patients were merged in the comparison of clinical outcomes. The clinical outcomes analysis of patients with different genotypes found that the objective response rates (ORR) of CT/TT genotypes were 34.38% and 43.02% (P=0.395), respectively. And the median progression free survival (PFS) of patients with CT/TT genotype and CC genotype were 7.5 and 9.7 months respectively, which was statistically significant (P=0.009). In terms of overall survival (OS), the median OS of the two genotypes were 19.3 and 20.1 (P=0.025), respectively. Adjusted in multivariate Cox regression analysis of PFS, CT/TT genotypes were an independent factor for PFS (OR=1.88, P=0.023). Additionally, of the 57 biopsy tissue specimens, gene expression analysis was conducted. And the results showed that the expression of KDR in cancer tissues of the patients with CT/TT genotypes were significantly higher than those of the CC genotype patients (P<0.001). Conclusion: Among advanced colorectal cancer patients treated by bevacizumab, the polymorphism 889 C>T of KDR may impact the clinical outcomes of bevacizumab first line treatment by influencing the mRNA expression of KDR.

[A clinical analysis of hepatic veno-occlusive disease after hematopoietic stem cell transplantation].

Objective: To analyze the outcome and the prognostic factors of hepatic veno-occlusive disease (HVOD) after hematopoietic stem cell transplantation (HSCT). Methods: A total of 797 patients receiving HSCT were analyzed retrospectively. The prophylaxis regimen of HVOD in the First Affiliated Hospital of Guangxi Medical University consisted of low molecular weight heparin and lipoprostaglandin E1 (PGE1). Results: Fifty-nine patients (7.4%) developed HVOD at 3-49 days after HSCT (median 12 days). Age younger than 15 years at transplant(HR= 6.47, P<0.001), busulphan conditioning (HR=6.40, P<0.001), thalassemia major (HR=6.35, P<0.001), allogeneic transplantation (HR=7.74, P=0.005) were univariate risk factors for HVOD. Multivariate analyses suggested that thalassemia major and busulphan conditioning were independently correlated with the development of HVOD. Conclusion: Thalassemia major and busulphan conditioning are independent risk factors for HVOD after HSCT.