AIM: To investigate effects of genistein, an inhibitor of protein tyrosine kinase and vanadate, the inhibitor of protein tyrosine phophorylation, on glutamate-induced Ca2+ entry in rat primary cultured corticocerebral neurons. METHODS: The effects of drug on cytoplasmic Ca2+ level ([Ca2+]i) were invesgated with Fura-2/AM fluorescence technique. RESULTS The increase in [Ca2+]i induced by glutamate was significantly reduced by genistein (from 1 to 30 μmol·L-1) and NMDA receptor antagonist MK-801 (1 μmol·L-1), not by nimodipine (1 μmol·L-1) and SK&F96365. Vanadate (from 1 to 30 μmol·L-1) significantly enhanced glutamine-induced [Ca2+]i response. CONCLUSION: Nimdipine-sensitive Ca2+ channel and SK&F96365-sensitive Ca2+ channels are not related to glutamate-induced Ca2+ entry. It is related to the activation of protein tyrosine kinase in rat primary cultured corticocerebral neurons.

Objective: To understand the pathogenesis of bisphosphonate-related osteonecrosis of the jaws (BRONJ) and to investigate its differential diagnosis, clinical manifestations, treatment and prevention. Methods: By analyzing the clinical data of 4 patients with BRONJ in the retrospective study with reviewing related literatures in the world to make a summary of it Results: Cases of 4 patients mainly presented recurring pain, discharging of pus and disposure and necrosis of the bone. 3 patients received surgical and antibiotics treatments, one of them had local infection which was under control by oral antibiotic. The other 2 patients had no infection and recurrence. Conclusion BRONJ is caused by jaw necrosis due to bisphosphonate inhibition of osteoclast function. For the reason that none of the treatments is unified and satisfied, we should focus on the risk factors in prevention. Appropriate surgery treatment could be well controlled the process of the BRONJ which should be popularization in our study.

Acute lymphoblastic leukemia is the commonest pediatric malignancy caused by the disturbed differentiation of hematopoietic stem cells. Due to the effective measure of individualized therapy, the outcome of ALL therapy has been improved dramatically in recent decades. The reduction of treatment intensity in favorable patient groups decreases acute and long-term toxicity, only for the high-risk groups the intensive chemotherapy is of value, and the different therapies should be used, depending on their different biologic features.Even with intensive therapy or new drugs, the outcome of relapsed ALL remains poor, the treatment could be turned to the molecularly defined targeted drugs and stem cell transplantation. What is more, the progress in the detection technique for minimal residual disease and pharmacogenomics help to estimate the sensitivity of chemotherapy and judge the prognosis, so as to provide the reliable objective foundation for the individualized therapy.In this review, the present states of individualized therapy in childhood acute lymphoblastic leukemia is discussed and summarized.
Child ; Genomics ; Humans ; Neoplasm, Residual ; drug therapy ; Precision Medicine ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy

OBJECTIVE: To explore the effect of posaconazole in the primary prevention of invasive fungal disease (IFD) in the induction therapy of childhood acute lymphoblastic leukemia (ALL). METHODS: From August 2018 to November 2020, 144 pediatric patients with ALL treated in Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University were selected, 88 cases received fluconazole as IFD prophylaxis (fluconazole prophylaxis group), 56 cases received posaconazole as IFD prophylaxis (posaconazole prophylaxis group). The incidence of IFD and treatment-related adverse reactions between the two groups were compared, and the safety of posaconazole was evaluated. RESULTS: The incidence of IFD in the fluconazole prophylaxis group was 20.4% (18/88), and in the posaconazole prophylaxis group was 7.1% (4/56). The incidence of IFD between the two groups was statistically significant different(P=0.030). There was no serious adverse reactions in the two groups. The incidence of mild adverse reactions in the posaconazole prophylaxis group (23.2%) was lower than that in the fluconazole prophylaxis group(39.8%), and the difference was statistically significant (P=0.039). There were 12 cases died in the fluconazole prophylaxis group and 4 in the posaconazole prophylaxis group, while no significant difference in the overall survival rate between the two groups (P=0.281). CONCLUSION The effect of posaconazole in the primary prophylaxis of IFD is better and incidence of adverse reactions is lower than fluconazole. Posaconazole can be tolerated, and expected to become the first-line primary prophylaxis drug for IFD during the induction remission therapy of childhood ALL.
Antifungal Agents/therapeutic use* ; Child ; Humans ; Induction Chemotherapy ; Mycoses/drug therapy* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Primary Prevention ; Triazoles

adrenocorticalcarcinoma；cortisolhypersecretion；hypokalemia；prognosis 【Objective】To analyze the prognostic determinants of adreno cortical carcinoma（ACC）inadults.【Methods】Alladult patients who were admitted to SunYat-sen Memorial Hospital，SunYat-sen University from December 2011 to March 2017 and pathologically diagnosed ACC were included in this study.Thec linical data and preoperative laboratory examinations of those patients were analyzed retrospectively. Overall survival or disease-free survival was calculated and survivalcurves were plotted by Kaplan-Meier and compared by log-rank test. Harzardratios（HRs） with their 95% confidenceintervals（CIs） were calculated by univariate and multivariate Coxregression model.【Results】The study included 20 adult patients with ACC， with a median follow-up of 13months （6~73 months）. The mean survival time of those patients was 49.2 months（6~73months），with a 1-year survival rate of 70.0%. The results of multivariate Coxregression analysis revealed that the presense of cortisol hypersecretion（HR=23.60，95%CI：2.49-223.79，P=0.006） and hypokalemia（HR=23.60，95%CI：2.49-223.79，P=0.006）were predictors of poorprognosis of ACC. Moreover，in 18 patients with completely resected ACC，the presense of hypokalemia resulted in a worse disease-free survival.【Conclusion】The presense of cortisol hypersecretion and hypokalemiaare independent risk factors associated with poorprognosis of ACC in adults.​

【Objective】To explore clinical manifestations and features of renal uric acid excretion in gout patients with obesity.【Methods】Totally 228 primary gout patients were enrolled and divided into three groups according to body mass index（BMI）. Clinical and fasting blood biochemical analysis data were collected. Indices of renal uric acid excretion were calculated according to 24 h urinary uric acid and urinary creatinine.【Results】The obese group（n = 44）was younger than overweight group（n = 88）and non-overweight group（n = 96）［43（32，57）years vs 55（45，65）years，58（45，67）years］，with earlier onset age［37（26，48）years vs 48（38，59）years］，higher serum uric acid［594（522，697）μmol/L vs 511（372，653）μmol/L］and had more hypercholesterolemia（56.8% vs 31.3%）and low density lipoproteinemia（59.1% vs 47.9%）compared with non-overweight group. The ratio of hypertriglyceridemia（43.5% and 37.5% vs 17.7%）and metabolic syndrome（50.0% and 36.4% vs 12.5%）in the overweight and obese group were both higher than non- overweight group. Fraction excretion of uric acid（FEUA）in obese group［5.5（3.6，7.4）% vs 7.0（5.2，9.8）%］was lower than non-overweight group，and the glomerular filtration load of uric acid［5.3（4.2，7.5）mg·min- 1 ·1.73 m- 2 vs 3.5（2.2，5.2）mg·min-1·1.73 m-2］in obese group was higher than that in non-overweight group（All P < 0.0167）. Multivariate regression analysis showed that overweight or obesity were negatively correlated with FEUA（All P < 0.05）.【Conclusion】High uric acid load of serum and glomerular filtration in gout patients with obesity may be due to the relative insufficiency of renal uric acid excretion.

OBJECTIVE: To analyze the clinical characteristics and treatment effects of children with acute megakaryoblastic leukemia without down syndrome (non-DS-AMKL). METHODS: The clinical data of 19 children with non-DS-AMKL treated in the Pediatric Hematology Ward in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from May 2008 to April 2018 were analyzed retrospectively. The clinical characteristics, laboratory test and treatment methods of the children were concluded. All patients were followed up to evaluate the effect of treatment. RESULTS: The 19 cases of children included nine male and ten female, the median age of onset was 2 years old. The clinical manifestations showed nonspecific. The median white blood cell of peripheral blood was 15.88×10 CONCLUSION Non-DS-AMKL was rare in children and difficult to be diagnosed. Determination of MICM classification as early as possible was helpful for diagnosis, and genetic testing played an important role for diagnosis and prognosis evaluation. Early hematopoietic stem cell transplantation in patients with CR after chemotherapy might be an effective way to cure AMKL.
Child ; Child, Preschool ; DEAD-box RNA Helicases ; DNA Helicases ; Down Syndrome ; Female ; Humans ; Leukemia, Megakaryoblastic, Acute/genetics* ; Male ; Prognosis ; Retrospective Studies ; Trisomy

OBJECTIVE: To investigate the clinical characteristics and treatment of pneumocystis carinii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL), in order to improve the early diagnosis and effective treatment. METHODS: Clinical data of five children with ALL developing PCP in the post-chemotherapy granulocyte deficiency phase were analyzed retrospectively. The clinical manifestations, laboratory tests, imaging findings, treatment methods and effect were summarized. RESULTS: The male-to-female ratio of the five children was 1∶4, and the median age was 5.5 (2.9-8) years old. All patients developed PCP during granulocyte deficiency phase after induction remission chemotherapy. The clinical manifestations were generally non-specific, including high fever, tachypnea, dyspnea, non-severe cough, and rare rales in two lungs (wet rales in two patients). Laboratory tests showed elevated C-reactive protein (CRP), serum procalcitonin (PCT), (1,3)-β-D-glucan (BDG), lactate dehydrogenase (LDH) and inflammatory factors including IL-2R, IL-6 and IL-8. Chest CT showed diffuse bilateral infiltrates with patchy hyperdense shadows. Pneumocystis carinii(PC) was detected in bronchoalveolar lavage fluid (BALF) or induced sputum by high-throughput sequencing in all patients. When PCP was suspected, chemotherapy was discontinued immediately, treatment of trimethoprim-sulfame thoxazole (TMP-SMX) combined with caspofungin against PC was started, and adjunctive methylprednisolone was used. Meanwhile, granulocyte-stimulating factor and gammaglobulin were given as the supportive treatment. All patients were transferred to PICU receiving mechanical ventilation due to respiratory distress during treatment. Four children were cured and one died. CONCLUSION PCP should be highly suspected in ALL children with high fever, dyspnea, increased LDH and BDG, and diffuse patchy hyperdense shadow or solid changes in lung CT. The pathogen detection of respiratory specimens should be improved as soon as possible. TMP/SMZ is the first-line drug against PCP, and the combination of Caspofungin and TMP/SMZ treatment for NH-PCP may have a better efficacy. Patients with moderate and severe NH-PCP may benefit from glucocorticoid.
Caspofungin/therapeutic use* ; Child ; Child, Preschool ; Dyspnea ; Female ; Humans ; Male ; Pneumonia, Pneumocystis/therapy* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Respiratory Sounds ; Retrospective Studies

OBJECTIVE: To investigate the difference of phonation patterns by dividing patients with vocal fold polyps and vocal nodules into two groups according to muscle tension patterns (MTP). METHOD: Fifty-six patients with vocal fold polyps and vocal nodules were divided into two groups according to phonation with MTP or not by video strobolaryngoscopy. RESULT: MTP could be found in 85% patients with vocal nodules and in 55.56% patients with vocal fold polyps. Significant difference was found in patients with/without MTP, and difference was also found in every type of MTP. CONCLUSION MTP lies in most patients with vocal nodules while only part of patients with vocal fold polyps, which indicated that vocal fold polyps and vocal nodules may demonstrate different phona
Adolescent ; Adult ; Aged ; Female ; Humans ; Laryngeal Diseases ; physiopathology ; Male ; Middle Aged ; Phonation ; Polyps ; physiopathology ; Vocal Cords ; pathology ; Voice Disorders ; physiopathology ; Young Adult

β-thalassemia is a monogenetic inherited hemolytic anemia, which results in a series of pathophysiological changes due to partial or complete inhibition of the synthesis of β-globin chain. The curative therapy for this disease is to reconstitute hematopoiesis, and transplantation with genetically modified autologous hematopoietic stem cells can avoid the major difficulties of traditional allogeneic hematopoietic stem cell transplantation，such as HLA matching and immune rejection. β-thalassemia gene therapy strategies mainly include gene integration and genome editing. The former relies on the development of lentiviral vectors and adds a fully functional HBB gene to the chromosome; the latter rapidly develops with the research of specific nuclease which can repair the HBB gene in situ. In this review, the latest progress of the two strategies in gene therapy of β-thalassemia is summarized.
Gene Editing ; Genetic Therapy ; Genetic Vectors ; Humans ; beta-Globins/genetics* ; beta-Thalassemia/therapy*