OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

Cardiovascular damage caused by cancer treatment has become an important cause of death for tumor survivors. With the recognition of cardiovascular diseases and cancer therapy-related cardiovascular toxicity (CTR-CVT) in tumor patients, noninvasive imaging technologies play pivotal roles in the risk stratification, early diagnosis, monitoring and follow-up for CTR-CVT. In recent years, the field of cardio-oncology has witnessed continual updates in diagnostic and therapeutic strategies, with several pertinent guidelines and expert consensus documents issued in China and abroad. However, there remains a conspicuous absence of systematic guidance documents on the application of imaging techniques in the clinical practice of cardio-oncology. Therefore, the Chinese Anti-Cancer Association Society of Integrative Cardio-oncology, the Ultrasound Branch of the Chinese Medical Association, and the Chinese Society of Echocardiography convened experts to formulate the "Chinese guideline for the clinical application of noninvasive imaging technology in accessing cancer therapy-related cardiovascular toxicity". Building upon the systematic evaluation of guidelines and the latest evidence-based medical research in the field of cardio-oncology domestically and abroad, and in conjunction with data derived from evidence-based medical research in China, this guideline proposes noninvasive imaging examination methods and monitoring strategies for CTR-CVT, aiming to further standardize and guide the clinical practice of multidisciplinary physicians specializing in cardio-oncology in China.

AIM To study the chemical constituents and their anti-inflammatory activities of stems and leaves of Lonicera confusa DC.METHODS The 80%methanol extract from stems and leaves of L.confusa DC was isolated and purified by Diaion HP20SS,Sephadex LH-20,HSCCC and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities were evaluated by measuring NO production of LPS-stimulated RAW264.7 cells in vitro.RESULTS Thirteen compounds were isolated and identified as benzyl alcohol-O-β-D-glucopyranosyl-(1 →6)-β-D-glucopyranoside(1),sweroside(2),epi-vogeloside(3),vogeloside(4),secologanoside(5),secoxyloganin(6),secologanin dimethyl acetal(7),methyl chlorogenate(8),apigenin-7-O-β-D-glucopyranoside(9),luteolin-7-O-β-D-glucopyranoside(10),rhoifolin(11),luteolin-7-O-α-L-arabinopyranosyl(1→6)-β-D-glucopyranoside(12),and lonicerin(13).Compounds 2-8,11-13 inhibited the NO production of LPS-induced cells.CONCLUSION Compound 1 is first isolated from family Lonicera,compounds 3,5,7,9,11,and 12 are obtained from the stems and leaves of this plant for the first time.Compounds 2-8,11-13 exhibited anti-inflammatory activities.

Objective:To establish a highly sensitive and quantitative detection method for ABL1 kinase region mutations,provide strong support for the early diagnosis and treatment of chronic myeloid leukemia(CML).Methods:Sampele from 35 CML patients who were initially tested negative for ABL1 kinase region mutations by Sanger sequencing were collected.The ABL1 kinase region mutation was detected by the fluorescence quantitative detection kit of Shanghai Yuanqi Biopharmaceutical Technology Co.,Ltd.The mutation rate was analyzed byΔΔCt value method.The relative mutation rate of the final ABL1 kinase region was determined by dividing the mutation rate by the expression level of the fusion gene.Results:Among the 35 CML patients initially tested negative for ABL1 mutations by the Sanger sequencing method,7 cases of T315I mutation,2 cases of T315A mutation,2 cases of Y253H mutation,and 1 cases of E255K mutation after detection of the new method.The relative mutation rates range from 0.1％to 19.42％,which could not be detected by Sanger sequencing method.Subsequently,this method was used to detect the ABL1 mutation in 126 CML patients,and the positive rate exceeded that of the Sanger sequencing method.The BCR-ABL1 gene expression significantly reduced or negative after adjusting treatment strategy based on the mutation situation.Conclusion:Compared with Sanger sequencing,fluorescence quantitative PCR has higher sensitivity and can screen for low-frequency ABL1 kinase mutations in the early stage.Moreover,it can also perform relative quantitative analysis,so the method has good clinical application prospects for detecting ABL1 mutation.

Objective:To investigate the molecular mechanism and distribution characteristics of RhD negative phenotypes in Han population of blood donors in Wuhu city.Methods:A total of 210 RhD-samples from August 2021 to August 2022 were screened by serological test and collected from Wuhu Central Blood Station for the voluntary blood donor population.Exons 1 and 10 of the RHD gene were amplificated by PCR to determine whether the samples had the RHD gene.Exons 1-10 of the RHD gene were amplificated by PCR and zygosity analysis were performed in 82 samples containing D gene,and Sanger sequencing was performed on 55 samples containing all RHD exons to determine the genotype.Results:Among 210 RhD-specimens,128 cases(60.38％)had RHD gene deletion.27 cases had partial exons of RHD,including 2 cases with RHD*DVI.3/RHD*01N.01,24 cases with RHD*01N.04/RHD*01N.01,and 1 case with RHD-CE(2-10)/RHD*01N.01.55 cases had retained all of 10 exons,including 4 cases with RHD*01/RHD*01N.01,6 cases with RHD*15/RHD*01N.01,1 case with RHD*01W.72/RHD*01N.01,1 case with RHD*15/RHD*01EL.01,39 cases with RHD*01EL.01/RHD*01N.01,and the remaining 4 cases were determined to have no RHD gene deletion by zygosity analysis and sequencing showed the presence of 1227G＞A mutation loci.Conclusion:There is polymorphism in the molecular mechanism of RhD-D gene in Wuhu blood donor population,among which RHD*01EL.01 and RHD*15 are the main variants in this region.The results of this study provide a theoretical basis for RhD blood group identification and clinical blood transfusion in this region.

Objective: To investigate the trends in mortality of malignant tumors in Ningbo City, Zhejiang Province from 2002 to 2022, so as to provide the evidence for formulating malignant tumor control strategies in Ningbo City. Methods The data regarding the mortality of malignant tumors in Ningbo City from 2002 to 2022 were collected through the Ningbo Municipal Death Cause Monitoring System, and the crude mortality and age-specific mortality of malignant tumors were calculated in Ningbo City. The mortality of malignant tumors was standardized by the population of the sixth National Population Census in China in 2010 (Chinese-standardized mortality) and the world standard population in 1960 (world-standardized mortality). The trends in mortality of malignant tumors were evaluated with annual percent change (APC) and average annual percent change (AAPC). Methods: The data regarding the mortality of malignant tumors in Ningbo City from 2002 to 2022 were collected through the Ningbo Municipal Death Cause Monitoring System, and the crude mortality and age-specific mortality of malignant tumors were calculated in Ningbo City. The mortality of malignant tumors was standardized by the population of the sixth National Population Census in China in 2010 (Chinese-standardized mortality) and the world standard population in 1960 (world-standardized mortality). The trends in mortality of malignant tumors were evaluated with annual percent change (APC) and average annual percent change (AAPC). Results: The crude mortality of malignant tumors was 186.43/105 to 221.24/105 in Ningbo City from 2002 to 2022, which showed a tendency towards a rise (AAPC=0.76%), and both the Chinese- (AAPC=-2.64%) and world-standardized mortality (AAPC=-2.74%) appeared a tendency towards a decline (all P<0.05). The world-standardized mortality of malignant tumors presented three changes in Ningbo City from 2002 to 2022, with a more remarkable decline from 2011 to 2018 (APC=-3.53%) than from 2002 to 2011 (APC=-2.10%) and from 2018 to 2022 (APC=-2.00%) (all P<0.05). The annual decline in mortality of malignant tumors was higher in men (Chinese-standardized mortality: AAPC=-2.68%; world-standardized mortality: AAPC=-2.75%) than in women (Chinese-standardized mortality: AAPC=-2.45%; world-standardized mortality: AAPC=-2.57%), and higher in urban areas (Chinese-standardized mortality: AAPC=-2.85%; world-standardized mortality: AAPC=-2.92%) than in rural areas (Chinese-standardized mortality: AAPC=-2.45%; world-standardized mortality: AAPC=-2.57%) (all P<0.05). The mortality of malignant tumors appeared a tendency towards a rise with age in Ningbo City, with the highest mortality in residents at ages of 85 years and older (1 447.13/105). Death from malignant tumors were responsible for 31.86% of all causes of death in Ningbo City, and the five most common causes of cancer death included lung cancer, liver cancer, gastric cancer, colorectal cancer and esophageal cancer. In addition, the world-standardized mortality of pancreatic cancer (AAPC=3.92%), prostate cancer (AAPC=4.71%), and cervical cancer (AAPC=1.60%) appeared a tendency towards a rise in Ningbo City (all P<0.05). Conclusions The crude mortality of malignant tumors appeared a tendency towards a rise in Ningbo City from 2002 to 2022, while the standardized mortality showed a tendency towards a decline. Management of malignant tumors should be given a high priority among men and rural residents, and lung cancer, liver cancer, gastric cancer, colorectal cancer and esophageal cancer should be emphasized.

Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect.

It is believed that the basic pathogenesis of oculomotor nerve paralysis （ONP） is qi and blood depletion and channel obstruction. Taking channel pattern differentiation as the core， it is recommended to use acupuncture mainly based on location， syndrome and channel deficiency-excess differentiation. Location and channel tropism differentiation mainly follows the principle of “where the channels and collaterals pass， the main treatment can reach”， and commonly uses acupuncture points on Dumai （督脉）， the hand Shaoyang （少阳） Sanjiao （三焦） channel， the hand Taiyang （太阳） small intestine channel， three yang channels of the foot， the hand Shaoyin （少阴） heart channel， the foot Jueyin （厥阴） liver channel， and others， and combines scalp acupuncture with electro-acupuncture to enhance channel stimulation. Pattern and channel tropism differentiation is to differentiate the entered channel according to clinical symptoms and zang-fu patterns. The differentiation of deficiency-excess should be payed attention to， and the principle of “supplementing the deficiency， and draining the excess” should be followed. The supplementing and draining method should be used rationally by considering the differences in the supplementing and draining acupoints themselves， as well as the actual condition of the patients. Simultaneously， it is suggested to combine manipulation and stimulation amount and effect in clinical practice.

Objective: To investigate the trends in incidence and mortality of gastric cancer in Ningbo City, Zhejiang Province from 2011 to 2022, so as to provide insights into improving gastric cancer control strategy. Methods: The incidence and mortality of gastric cancer in Ningbo City from 2011 to 2022 were collected through Ningbo Municipal Chronic Disease and Cause of Death Monitoring System. The incidence and mortality of gastric cancer were calculated, and standardized by the data from the Sixth Chinese National Population Census in 2020 (Chinese-standardized rate) and the world standard population first introduced by Segi in 1960 (world-standardized rate). The trends in incidence and mortality of gastric cancer were evaluated using annual percent change (APC) and average annual percent change (AAPC). Results : The crude incidence of gastric cancer was 45.69/105 in Ningbo City from 2011 to 2022, with no significant changing patterns seen during the study period (AAPC=-0.02%, P>0.05), and the Chinese- and world-standardized incidence of gastric cancer was 28.61/105 and 21.87/105, which both appeared a tendency towards a decline (AAPC=-3.19% and -3.05%, both P<0.05). The crude, Chinese-standardized and world-standardized mortality rates of gastric cancer were 28.56/105, 17.07/105 and 12.57/105, respectively, all showing a tendency towards a decline (AAPC=-3.00%, -6.26% and -6.34%, all P<0.05). The Chinese- and world-standardized incidence and mortality of gastric cancer all appeared a tendency towards a decline in urban (AAPC=-2.72%, -2.53%, -5.91% and -5.96%, all P<0.05) and rural areas (AAPC=-3.61%, -3.53%, -6.79% and -6.89%, all P<0.05), and the Chinese- and world-standardized incidence and mortality of gastric cancer were significantly higher among urban residents than among rural residents. The Chinese- and world-standardized incidence and mortality of gastric cancer all appeared a tendency towards a decline among men (AAPC=-3.18%, -3.00%, -5.82% and -5.91%, all P<0.05) and women (AAPC=-2.98%, -2.90%, -7.12% and -7.12%, all P<0.05), and the Chinese- and world-standardized incidence and mortality of gastric cancer was significantly higher among men than among women. In addition, the crude incidence and mortality of gastric cancer both appeared a tendency towards a rise with age among residents in Ningbo City (both P<0.05). Conclusions The incidence and mortality of gastric cancer both appeared a tendency towards a decline in Ningbo City from 2011 to 2022; however, the incidence and mortality remained high. Males and urban residents should be given a high priority for gastric cancer control, and gastric cancer screening should be strengthened among individuals at ages of 40 years and older.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve