1.Singapore consensus statements on the management of obstructive sleep apnoea.
Leong Chai LEOW ; Chuen Peng LEE ; Sridhar VENKATESWARAN ; Michael Teik Chung LIM ; Oon Hoe TEOH ; Ruth CHANG ; Yam Cheng CHEE ; Khai Beng CHONG ; Ai Ping CHUA ; Joshua GOOLEY ; Hong Juan HAN ; Nur Izzianie KAMARUDDIN ; See Meng KHOO ; Lynn Huiting KOH ; Shaun Ray Han LOH ; Kok Weng LYE ; Mark IGNATIUS ; Yingjuan MOK ; Jing Hao NG ; Thun How ONG ; Chu Qin PHUA ; Rui Ya SOH ; Pei Rong SONG ; Adeline TAN ; Alvin TAN ; Terry TAN ; Jenny TANG ; David TAY ; Jade TAY ; Song Tar TOH ; Serene WONG ; Chiang Yin WONG ; Mimi YOW
Annals of the Academy of Medicine, Singapore 2025;54(10):627-643
INTRODUCTION:
Obstructive sleep apnoea (OSA) is common in Singapore, with moderate to severe OSA affecting around 30% of residents. These consensus statements aim to provide scientifically grounded recommendations for the management of OSA, standar-dise the management of OSA in Singapore and promote multidisciplinary collaboration.
METHOD:
An expert panel, which was convened in 2024, identified several areas of OSA management that require guidance. The expert panel reviewed the current literature and developed consensus statements, which were later independently voted on using a 3-point Likert scale (agree, neutral or disagree). Consensus (total ratings of agree and neutral) was set a priori at ≥80% agreement. Any statement not reaching consensus was excluded.
RESULTS:
The final consensus included 49 statements that provide guidance on the screening, diagnosis and management of adults with OSA. Additionally, 23 statements on the screening, diagnosis and management of paediatric OSA achieved consensus. These 72 consensus statements considered not only the latest clinical evidence but also the benefits and harms, resource implications, feasibility, acceptability and equity impact of the recommendations.
CONCLUSION
The statements presented in this paper aim to guide clinicians based on the most updated evidence and collective expert opinion from sleep specialists in Singapore. These recommendations should augment clinical judgement rather than replace it. Management decisions should be individualised, taking into account the patient's clinical characteristics, as well as patient and caregiver concerns and preferences.
Humans
;
Sleep Apnea, Obstructive/diagnosis*
;
Singapore
;
Consensus
;
Adult
2.Association of Body Mass Index with All-Cause Mortality and Cause-Specific Mortality in Rural China: 10-Year Follow-up of a Population-Based Multicenter Prospective Study.
Juan Juan HUANG ; Yuan Zhi DI ; Ling Yu SHEN ; Jian Guo LIANG ; Jiang DU ; Xue Fang CAO ; Wei Tao DUAN ; Ai Wei HE ; Jun LIANG ; Li Mei ZHU ; Zi Sen LIU ; Fang LIU ; Shu Min YANG ; Zu Hui XU ; Cheng CHEN ; Bin ZHANG ; Jiao Xia YAN ; Yan Chun LIANG ; Rong LIU ; Tao ZHU ; Hong Zhi LI ; Fei SHEN ; Bo Xuan FENG ; Yi Jun HE ; Zi Han LI ; Ya Qi ZHAO ; Tong Lei GUO ; Li Qiong BAI ; Wei LU ; Qi JIN ; Lei GAO ; He Nan XIN
Biomedical and Environmental Sciences 2025;38(10):1179-1193
OBJECTIVE:
This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study.
METHODS:
A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants.
RESULTS:
Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m 2) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m 2) and obesity (≥ 28.0 kg/m 2) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m 2 ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses.
CONCLUSION
This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans
;
Body Mass Index
;
China/epidemiology*
;
Male
;
Female
;
Middle Aged
;
Prospective Studies
;
Rural Population/statistics & numerical data*
;
Aged
;
Follow-Up Studies
;
Adult
;
Mortality
;
Cause of Death
;
Obesity/mortality*
;
Overweight/mortality*
3.Treatment of patent ductus arteriosus in very preterm infants in China.
Ai Min QIAN ; Rui CHENG ; Xin Yue GU ; Rong YIN ; Rui Miao BAI ; Juan DU ; Meng Ya SUN ; Ping CHENG ; K L E E shoo K LEE ; Li Zhong DU ; Yun CAO ; Wen Hao ZHOU ; You Yan ZHAO ; Si Yan JIANG
Chinese Journal of Pediatrics 2023;61(10):896-901
Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant
;
Infant, Newborn
;
Male
;
Humans
;
Female
;
Ductus Arteriosus, Patent/drug therapy*
;
Infant, Premature
;
Cross-Sectional Studies
;
Ibuprofen/therapeutic use*
;
Infant, Very Low Birth Weight
;
Persistent Fetal Circulation Syndrome
;
Infant, Premature, Diseases/therapy*
4.Tetrahydropalmatine alleviated diabetic neuropathic pain by inhibiting activation of microglia via p38 MAPK signaling pathway.
Lian-Zhi CHENG ; Jia-Mei ZHOU ; Jun-Long MA ; Fan-Jing WANG ; Kai CHENG ; Qian CHEN ; Hui-Lun YUAN ; Ai-Juan JIANG
China Journal of Chinese Materia Medica 2022;47(9):2533-2540
Neuropathic pain is one of the common complications of diabetes. Tetrahydropalmatine(THP) is a main active component of Corydalis Rhizoma with excellent anti-inflammatory and pain-alleviating properties. This study aims to investigate the therapeutic effect of THP on diabetic neuropathic pain(DNP) and the underlying mechanism. High-fat and high-sugar diet(4 weeks) and streptozotocin(STZ, 35 mg·kg~(-1), single intraperitoneal injection) were employed to induce type-2 DNP in rats. Moreover, lipopolysaccharide(LPS) was used to induce the activation of BV2 microglia in vitro to establish an inflammatory cellular model. Fasting blood glucose(FBG) was measured by a blood glucose meter. Mechanical withdrawal threshold(MWT) was assessed with von Frey filaments, and thermal withdrawal latency(TWL) with hot plate apparatus. The protein expression levels of OX42, inducible nitric oxide synthase(iNOS), CD206, p38, and p-p38 were determined by Western blot, the fluorescence expression levels of OX42 and p-p38 in the dorsal horn of the rat spinal cord by immunofluorescence, the mRNA content of p38 and OX42 in rat spinal cord tissue by qRT-PCR, and levels of nitric oxide(NO), interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and serum fasting insulin(FINS) by enzyme-linked immunosorbent assay(ELISA). RESULTS:: showed that the mo-del group demonstrated significant decrease in MWT and TWL, with pain symptoms. THP significantly improved the MWT and TWL of DNP rats, inhibited the activation of microglia and p38 MAPK signaling pathway in rat spinal cord, and ameliorated its inflammatory response. Meanwhile, THP promoted the change of LPS-induced BV2 microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, suppressed the activation of the p38 MAPK signaling pathway, decreased the expression levels of inflammatory factors NO, IL-1β, IL-6, and TNF-α, and increased the expression level of anti-inflammatory factor IL-10. The findings suggested that THP can significantly ameliorate the pain symptoms of DNP rats possibly by inhibiting the inflammatory response caused by M1 polarization of microglia via the p38 MAPK pathway.
Animals
;
Berberine Alkaloids
;
Blood Glucose/metabolism*
;
Diabetes Mellitus
;
Diabetic Neuropathies/genetics*
;
Interleukin-10
;
Interleukin-6/metabolism*
;
Lipopolysaccharides/pharmacology*
;
Microglia
;
Neuralgia/metabolism*
;
Rats
;
Rats, Sprague-Dawley
;
Signal Transduction
;
Spinal Cord/metabolism*
;
Streptozocin/therapeutic use*
;
Tumor Necrosis Factor-alpha/metabolism*
;
p38 Mitogen-Activated Protein Kinases/metabolism*
5.Effect of Carvacrol on the Biological Behavior of Leukemia Cells and Its Mechanism.
Yan LIANG ; Ai-Ying YANG ; Min LIU ; Yan-Juan CHENG ; Si-Bin ZANG ; Jun HUANG ; Yuan-Yan TANG ; Zhi-Ping HUANG
Journal of Experimental Hematology 2022;30(2):393-399
OBJECTIVE:
To explore the effect of carvacrol on the biological behavior of leukemia cells and its regulation to circ-0008717/miR-217 molecular axis.
METHODS:
Human acute lymphoblastic leukemia cells Molt-4 were cultured in vitro, and different concentrations of carvacrol were added to the cells. si-NC and si-circ-0008717 were transfected into Molt-4 cells (si-NC group, si-circ-0008717 group). pcDNA, pcDNA-circ-0008717, anti-miR-NC, anti-miR-217 were transfected into Molt-4 cells and then added to carvacrol-treated cells (carvacrol+pcDNA group, carvacrol+pcDNA-circ-0008717 group, carvacrol+anti-miR-NC group, carvacrol+anti-miR-217 group). MTT, plate clone formation experiment, and flow cytometry were used to detect the viability of the cell, colony formation number, and apoptosis rate of cells, respectively. The RT-qPCR method was used to detect the expression levels of circ-0008717 and miR-217. The dual luciferase reporter gene experiment was used to detect the targeting relationship between circ-0008717 and miR-217.
RESULTS:
After carvacrol treatment, the cell viability decreased significantly (r=-0.9405), expression level of circ-0008717 decreased (r=-0.9117), colonies formed number decreased (r=-0.9256), while the cell apoptosis rate increased (r= 0.8464), and the expression level of miR-217 increased (r=0.9468). Compared with the si-NC group, the expression level of miR-217 in si-circ-0008717 group increased (P<0.001), the cell apoptosis rate increased (P<0.001), while cell viability decreased (P<0001), the number of colonies formed decreased (P<0.001). Compared with the carvacrol+pcDNA group, the cell viability of the carvacrol+pcDNA-circ-0008717 group increased (P<0.001), the number of colonies formed increased (P<0.001), while the cell apoptosis rate decreased (P<0.001). circ-0008717 could target miR-217. The cell viability of the carvacrol+anti-miR-217 group increased (P<0.001), and the number of colonies formed increased (P<0.001), while the cell apoptosis rate decreased (P<0001) as compared with the carvacrol+anti-miR-NC group.
CONCLUSION
Carvacrol can promote the expression of miR-217 by down-regulating the expression of circ-0008717, thereby reducing the proliferation and cloning ability of leukemia cells and promoting cell apoptosis.
Antagomirs
;
Apoptosis
;
Cell Line, Tumor
;
Cell Proliferation
;
Cymenes
;
Humans
;
Leukemia
;
MicroRNAs/genetics*
6.Expression and Clinical Significance of MMSA-8 and MMSA-1 in Bone Marrow of Patients with M2 Acute Myeloid Leukemia.
Yan LIANG ; Ai-Ying YANG ; Min LIU ; Yan-Juan CHENG ; Si-Bin ZANG ; Jun HUANG ; Yuan-Yan TANG ; Zhi-Ping HUANG
Journal of Experimental Hematology 2022;30(4):1018-1021
OBJECTIVE:
To detect the expression of multiple myeloma-associated antigen (MMSA)-8 and MMSA-1 in bone marrow mononuclear cells of patients with acute myeloid leukemia, and explore their roles in acute myeloid leukemia.
METHODS:
A total of 83 patients with M2 acute myeloid leukemia in our hospital from January 2019 to January 2020 were selected as research group, during the same period, 15 patients diagnosed iron deficiency anemia were selected as control group. Real-time fluorescence quantitative PCR was used to detect the levels of MMSA-8 and MMSA-1 in bone marrow mononuclear cells. Patients in the research group were divided into remission and non remission according to the clinical curative effect, and were divided into good prognosis, medium prognosis, and poor prognosis according to the prognosis. The relationship between MMSA-8, MMSA-1 and clinical efficacy, prognosis was analyzed. In addition, the general data of patients in the research group were collected, including white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), and percentage of bone marrow progenitor cells at admission. Pearson method was used to analyze the correlation between MMSA-8, MMSA-1 and clinical data, and MMSA-8 and MMSA-1.
RESULTS:
The analysis results about mRNA levels of MMSA-8 and MMSA-1 in bone marrow mononuclear cells of patients showed that patients in the research group were significantly higher than those in the control group (P<0.05); In the research group, patients without remission were also significantly higher than those with remission, as well as those with medium and poor prognosis than with good prognosis, while only mRNA level of MMSA-1 in patients with poor prognosis was significantly higher than those with medium prognosis (P<0.05). Pearson analysis showed that MMSA-8, MMSA-1 were positively correlated with WBC (r=0.468, r=0.516), and MMSA-8 was positively correlated with MMSA-1 (r=0.318).
CONCLUSION
The levels of MMSA-8 and MMSA-1 in bone marrow mononuclear cells of patients with M2 acute myeloid leukemia are increased, which are closely related to the occurrence and development of the disease, and have certain value for the prognosis.
Bone Marrow
;
Humans
;
Leukemia, Myeloid, Acute/genetics*
;
Multiple Myeloma/genetics*
;
Prognosis
;
RNA, Messenger
7.A multicenter epidemiological study of acute bacterial meningitis in children.
Cai Yun WANG ; Hong Mei XU ; Jiao TIAN ; Si Qi HONG ; Gang LIU ; Si Xuan WANG ; Feng GAO ; Jing LIU ; Fu Rong LIU ; Hui YU ; Xia WU ; Bi Quan CHEN ; Fang Fang SHEN ; Guo ZHENG ; Jie YU ; Min SHU ; Lu LIU ; Li Jun DU ; Pei LI ; Zhi Wei XU ; Meng Quan ZHU ; Li Su HUANG ; He Yu HUANG ; Hai Bo LI ; Yuan Yuan HUANG ; Dong WANG ; Fang WU ; Song Ting BAI ; Jing Jing TANG ; Qing Wen SHAN ; Lian Cheng LAN ; Chun Hui ZHU ; Yan XIONG ; Jian Mei TIAN ; Jia Hui WU ; Jian Hua HAO ; Hui Ya ZHAO ; Ai Wei LIN ; Shuang Shuang SONG ; Dao Jiong LIN ; Qiong Hua ZHOU ; Yu Ping GUO ; Jin Zhun WU ; Xiao Qing YANG ; Xin Hua ZHANG ; Ying GUO ; Qing CAO ; Li Juan LUO ; Zhong Bin TAO ; Wen Kai YANG ; Yong Kang ZHOU ; Yuan CHEN ; Li Jie FENG ; Guo Long ZHU ; Yan Hong ZHANG ; Ping XUE ; Xiao Qin LI ; Zheng Zhen TANG ; De Hui ZHANG ; Xue Wen SU ; Zheng Hai QU ; Ying ZHANG ; Shi Yong ZHAO ; Zheng Hong QI ; Lin PANG ; Cai Ying WANG ; Hui Ling DENG ; Xing Lou LIU ; Ying Hu CHEN ; Sainan SHU
Chinese Journal of Pediatrics 2022;60(10):1045-1053
Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ2=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent
;
Brain Abscess
;
Child
;
Child, Preschool
;
Escherichia coli
;
Female
;
Humans
;
Hydrocephalus
;
Infant
;
Infant, Newborn
;
Male
;
Meningitis, Bacterial/epidemiology*
;
Retrospective Studies
;
Streptococcus agalactiae
;
Streptococcus pneumoniae
;
Subdural Effusion
;
beta-Lactamases
8.Exploring Anti-inflammation Mechanism of Pien Tze Huang via Regulating of Microglia Polarization
Hai-yang SHU ; Dan-cai FAN ; Ning ZHAO ; Cheng LYU ; Ai-ping LYU ; Xiao-juan HE
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(5):48-53
Objective::To investigate the anti-inflammation mechanism of Pien Tze Huang (PTH) via regulating microglia polarization. Method::The experiment was divided into five groups, Blank, M1[lipopolysaccharide (LPS) 100 μg·L-1+ interferon-
9.Efficacy of Hyper-CVAD/MA and CHALL-01 regimens in the treatment of Philadelphia chromosome-positive adult acute lymphoblastic leukemia patients under 60 years old.
Ai Jie HUANG ; Li Bing WANG ; Juan DU ; Gu Sheng TANG ; Hui CHENG ; Sheng Lan GONG ; Lei GAO ; Hui Ying QIU ; Xiong NI ; Jie CHEN ; Li CHEN ; Wei Ping ZHANG ; Jian Min WANG ; Jian Min YANG ; Xiao Xia HU
Chinese Journal of Hematology 2019;40(8):625-632
Objective: To compare the difference of efficacy between traditional Hyper-CVAD/MA regimen and the adolescents inspired chemotherapy regimen, CH ALL-01, in treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) . Methods: In this study we retrospectively analyzed 158 Ph(+) ALL patients receiving Hyper-CVAD/MA regimen (n=63) or CHALL-01 regimen (n=95) in our center and Changzheng hospital from January 2007 to December 2017, excluding patients with chronic myeloid leukemia in blast crisis. Tyrosine kinase inhibitor (TKI) was administered during induction and consolidation chemotherapy. Patients who underwent hematopoietic stem cell transplantation received TKI as maintenance therapy. Results: Of them, 91.1% (144/158) patients achieved complete remission (CR) after 1-2 courses of induction. CR rate was 90.5% (57/63) for patients in Hyper-CVAD/MA group and 91.6% (87/95) for patients in CHALL-01 group. There was no difference in CR rates between the two groups (χ(2)=0.057, P=0.811) . The last follow-up was June 2018. A cohort of 134 CR patients could be used for further analysis, among them, 53 patients received Hyper-CVAD/MA regimen and other 81 patients received CHALL-01 regimen. The molecular remission rates were significantly higher in CHALL-01 group (complete molecular response: 44.4%vs 22.6%; major molecular response: 9.9% vs 18.9%) (χ(2)=7.216, P=0.027) . For the patients in Hyper-CVAD/MA group, the 4-year overall survival (OS) was 44.81% (95%CI: 30.80%-57.86%) and the 4-year disease free survival (DFS) was 37.95% (95%CI: 24.87%-50.93%) . For patients received CHALL-01 regimen, the 4-year OS was 55.63% (95%CI: 39.07%-69.36%) (P=0.037) and 4 year DFS was 49.06% (95%CI: 34.24%-62.29%) (P=0.015) , while there was no significant difference in 4 year cumulative incidence of relapse (CIR) (P=0.328) or cumulative incidence of nonrelapse mortality (CI-NRM) (P=0.138) . The rate of pulmonary infection was lower in patients received CHALL-01 regimen compared with patients received Hyper-CVAD regimen (43.4% vs 67.9%, χ(2)=7.908, P=0.005) . Conclusions: Outcome with CHALL-01 regimen appeared better than that with the Hyper-CVAD/MA regimen in Ph(+) ALL, which has lower incidence of pulmonary infection, higher molecular remission rate and better OS and DFS.
Adult
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Cyclophosphamide
;
Dexamethasone
;
Doxorubicin
;
Humans
;
Middle Aged
;
Philadelphia Chromosome
;
Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
;
Retrospective Studies
;
Vincristine
10. Side Effect and Attenuation of Triptolide
Bin LIU ; Dan-ping FAN ; Hai-yang SHU ; Xiao-juan HE ; Cheng LYU ; Ai-ping LYU
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(20):181-190
Triptolide (TP) is a kind of epoxy diterpene lactone compound extracted from xylem of Tripterygium wilfordii (TWHF). It is one of the main active components of TWHF, with anti-inflammatory, immunomodulatory and anti-tumor activities and pharmacological effect. It can be used in the treatment of rheumatoid arthritis and such cancers as leukemia, breast cancer, pancreatic cancer and lung cancer. In recent years, TP has been gradually applied in clinic and basic research, with a certain curative effect. But it also has certain side effect on digestive system, urinary system, reproductive system, circulatory system and immune system, including liver dysfunction, reduced fertility, chest tightness, heart palpitations, bradycardia, atrioventricular block, arrhythmia, kidney dysfunction, lymphoid organ atrophy, lymphoid tissue necrosis of lymphocytes, and reduction in the number of cells, impaired immune function. These toxic and side effect have greatly restricted the clinical application of TP. In the meantime, the researches and development related to preparations of TP have also been restricted, which has aroused wide attention from clinicians and researchers. To improve the therapeutic effect of TP and reduce the toxicity of TP in the process of application, domestic and foreign researchers have made a lot of studies and attempts, such as changing the chemical structure of TP to improve its solubility, developing drug delivery system to reduce its toxicity and using combination therapy with traditional Chinese herbal medicines to increase efficiency and reduce toxicity. In this paper, the toxic dose and mechanism of TP, TP's derivatives, drug loading system, compatibility and attenuation were integrated to provide ideas for further researches on toxicity and attenuation of TP.

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