Evidence-based evaluation of the global cancer-associated thromboembolism risk assessment tools / 中国药房

OBJECTIVE To evaluate the global cancer-associated thromboembolism risk assessment tools based on evidence- based methods， and to provide methodological reference and evidence-based basis for constructing a specific tool in China. METHODS A comprehensive search was conducted on 6 databases， including CNKI， Wanfang data， VIP， CBM， PubMed， and Embase， as well as on the websites of NCCN， ASCO， ESMO and so on with a deadline of June 30， 2022. Furthermore， a supplementary search was conducted in January 2023. The essential characteristics and methodological quality of included risk assessment tools were described and analyzed qualitatively， focusing on comparing each assessment stratification ability. RESULTS Totally 14 risk assessment tools were included in the study， with a sample size of 208-18 956 cases and an average age distribution of 53.1-74.0 years. The applicable population included outpatient cancer student@sina.com patients， lymphoma patients， and multiple myeloma patients，etc. The common predictive factors were body mass index， venous thromboembolism history， and tumor site. All tools had undergone methodological validation， with 9 presented in a weighted scoring format. Only seven tools were used simultaneously for specificity， sensitivity， negative predictive value （NPV）， positive predictive value （PPV） and area under the curve （AUC） or C statistical analysis. CONCLUSIONS The risk of bias in constructing existing tools is high， and the heterogeneity of tool validation results is significant. The overall methodological quality must be improved， and its risk stratification ability must also be investigated. There are still certain limitations in clinical practice in China.

Extralesional triamcinolone acetonide injection in the treatment of small chalazion

Purpose: To evaluate the effect of extralesional triamcinolone acetonide (TA) injection in the treatment of small chalazion (diameter ? 5 mm). Methods: Prospective interventional clinal study that included patients diagnosed as chalazion of small size not responding to conservative management for at least 2 weeks. All patients were treated with extralesional TA injection (4 mg). Successful resolution of a chalazion was defined as a decrease in size to 1 mm or smaller. Results: Thirty?eight patients were included in the study. The resolution was achieved in 33 (87%) patients. Nineteen (50%) patients had complete resolution after the first injection, and 13 (34.2%) patients had complete resolution after the second injection. Chalazion near the lower punctum needed more times of injections than those elsewhere (P = 0.02). Conclusions: Extralesional TA injection is effective in the treatment of both primary and recurred small chalazia. It is a simple and cost?saving procedure and can be considered an alternative first?line treatment for small chalazion.

Inhibitory Effect of Jinkui Shenqi Pills on Glucocorticoid-Enhanced Axial Length Elongation in Experimentally Myopic Guinea Pigs / 中国结合医学杂志

OBJECTIVE@#To explore the underlying mechanism of inhibition by Jinkui Shenqi Pills (JKSQP) on glucocorticoid-enhanced axial length elongation in experimental lens-induced myopia (LIM) guinea pigs.@*METHODS@#Sixty 2-week old male guinea pigs were randomly divided into 4 groups with 15 guinea pigs in each group, according to the random numbers generated by SPSS software: control, LIM, saline and JKSQP groups. The control group includes animals with no treatment, while the guinea pigs in the other 3 groups received lens-induced myopization on the right eyes throughout the experiment (for 8 weeks). The saline and JKSQP groups were given daily intraperitoneal injections of 10 mg/kg hydrocortisone for 2 consecutive weeks at the same time, and then orally administered either saline or JKSQP [13.5 g/(kg•d) for 6 consecutive weeks. Body weight, anal temperature and animal appearance were observed and recorded to evaluate the GC-associated symptoms. The ocular parameters, including refraction and axial length, were measured by streak retinoscopy and A-scan ultrasonography, respectively. The levels of plasma hormones associated with the hypothalamic-pituitary-adrenal axis (HPAA), including free triiodothyronine, free thyroxine, estradiol and testosterone, were measured by radioimmunoassay, and cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate were measured by enzyme-linked immunosorbent assay. In addition, the mRNA and protein expressions of retinal amphiregulin (AREG) was measured by quantitative real-time polymerase chain reaction and Western blotting, respectively.@*RESULTS@#JKSQP effectively increased body weight and anal temperature, improved animal appearance and suppressed axial length elongation in glucocorticoid-enhanced myopic guinea pigs with normalization of 4 HPAA-associated plasma hormones (all P<0.05). The plasma level of cAMP was significantly increased, whereas the plasma level of cGMP and the mRNA and protein expressions of retinal AREG were decreased after treatment with JKSQP (all P<0.05).@*CONCLUSION@#JKSQP exhibited a significant inhibitory effect on axial length elongation with decreased expression of AREG in the retina, and normalized 4 HPAA-associated plasma hormones and the expression of cAMP and cGMP in GC-enhanced myopic guinea pigs.

A prospective study on the development and application verification of the quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology / 中华烧伤杂志

Objective: To develop a quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology, and to verify its accuracy and feasibility in clinical application. Methods: The method of prospective observational study was adopted. From April 2019 to January 2022, 59 patients with pathological scars (totally 107 scars) who met the inclusion criteria were admitted to the First Medical Center of Chinese PLA General Hospital, including 27 males and 32 females, aged 33 (26, 44) years. Based on photo modeling technology, a software for measuring three-dimensional morphological parameters of pathological scars was developed with functions of collecting patients' basic information, and scar photography, three-dimensional reconstruction, browsing the models, and generating reports. This software and the clinical routine methods (vernier calipers, color Doppler ultrasonic diagnostic equipment, and elastomeric impression water injection method measurement) were used to measure the longest length, maximum thickness, and volume of scars, respectively. For scars with successful modelling, the number, distribution of scars, number of patients, and the longest length, maximum thickness, and volume of scars measured by both the software and clinical routine methods were collected. For scars with failed modelling, the number, distribution, type of scars, and the number of patients were collected. The correlation and consistency of the software and clinical routine methods in measuring the longest length, maximum thickness, and volume of scars were analyzed by unital linear regression analysis and the Bland-Altman method, respectively, and the intraclass correlation coefficients (ICCs), mean absolute error (MAE), and mean absolute percentage error (MAPE) were calculated. Results: A total of 102 scars from 54 patients were successfully modeled, which located in the chest (43 scars), in the shoulder and back (27 scars), in the limb (12 scars), in the face and neck (9 scars), in the auricle (6 scars), and in the abdomen (5 scars). The longest length, maximum thickness, and volume measured by the software and clinical routine methods were 3.61 (2.13, 5.19) and 3.53 (2.02, 5.11) cm, 0.45 (0.28, 0.70) and 0.43 (0.24, 0.72) cm, 1.17 (0.43, 3.57) and 0.96 (0.36, 3.26) mL. The 5 hypertrophic scars and auricular keloids from 5 patients were unsuccessfully modeled. The longest length, maximum thickness, and volume measured by the software and clinical routine methods showed obvious linear correlation (with r values of 0.985, 0.917, and 0.998, P<0.05). The ICCs of the longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods were 0.993, 0.958, and 0.999 (with 95% confidence intervals of 0.989-0.995, 0.938-0.971, and 0.998-0.999, respectively). The longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods had good consistency. The Bland-Altman method showed that 3.92% (4/102), 7.84% (8/102), and 8.82% (9/102) of the scars with the longest length, maximum thickness, and volume respectively were outside the 95% consistency limit. Within the 95% consistency limit, 2.04% (2/98) scars had the longest length error of more than 0.5 cm, 1.06% (1/94) scars had the maximum thickness error of more than 0.2 cm, and 2.15% (2/93) scars had the volume error of more than 0.5 mL. The MAE and MAPE of the longest length, maximum thickness, and volume of scars measured by the software and clinical routine methods were 0.21 cm, 0.10 cm, 0.24 mL, and 5.75%, 21.21%, 24.80%, respectively. Conclusions: The quantitative evaluation software for three-dimensional morphology of pathological scars based on photo modeling technology can realize the three-dimensional modeling and measurement of morphological parameters of most pathological scars. Its measurement results were in good consistency with those of clinical routine methods, and the errors were acceptable in clinic. This software can be used as an auxiliary method for clinical diagnosis and treatment of pathological scars.

Analysis of the characteristics of SPTB gene variants among 16 children with Hereditary spherocytosis / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical characteristics and spectrum of SPTB gene variants among 16 Chinese children with Hereditary spherocytosis (HS) and explore their genotype-phenotype correlation.@*METHODS@#Sixteen children who were diagnosed with HS at the Affiliated Hospital of Capital Institute of Pediatrics from November 2018 to July 2022 were selected as the research subjects. Genetic testing was carried out by whole exome sequencing. Candidate variants were verified by Sanger sequencing and subjected to bioinformatic analysis and prediction of 3D structure of the protein. Correlation between the SPTB genotypes and clinical phenotypes was analyzed using Chi-squared test.@*RESULTS@#The male-to-female ratio of the HS patients was 6 : 10, with the median age being 7-year-and-10-month. Clinical features of the patients have included anemia, reticulocytosis and gradual onset of splenomegaly. Mild, moderate and severe anemia have respectively occurred in 56.25% (9/16), 31.25% (5/16) and 12.50% (2/16) of the patients. SPTB gene variants were detected in all patients, among which 10 were unreported previously and 7 were de novo in origin. Loss of function (LOF) variants accounted for 93.75% (15/16). Only one missense variant was detected. Eleven, 4 and 1 of the variants had occurred in the repeat domain, CH1 domain, and dimerization domain, respectively. There was no significant correlation between the type or domain of the SPTB gene variants with the clinical features such as severity of anemia (x² = 3.345, P > 0.05). All of the variants were predicted to be pathogenic or likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics.@*CONCLUSION@#Mild to moderate anemia are predominant clinical features of the HS children harboring a SPTB gene variant, for which LOF variants are the main mutational type. The clinical feature of HS is unaffected by the type of the variants.

Difference in liver injury induced by dictamnine between males and females: based on untargeted metabolomics / 中国中药杂志

In recent years, reports of adverse reactions related to traditional Chinese medicine(TCM) have been on the rise, especially some traditionally considered "non-toxic" TCM(such as Dictamni Cortex). This has aroused the concern of scholars. This study aims to explore the metabolomic mechanism underlying the difference in liver injury induced by dictamnine between males and females through the experiment on 4-week-old mice. The results showed that the serum biochemical indexes of liver function and organ coefficients were significantly increased by dictamnine(P<0.05), and hepatic alveolar steatosis was mainly observed in female mice. However, no histopathological changes were observed in the male mice. Furthermore, a total of 48 differential metabolites(such as tryptophan, corticosterone, and indole) related to the difference in liver injury between males and females were screened out by untargeted metabolomics and multivariate statistical analysis. According to the receiver operating characteristic(ROC) curve, 14 metabolites were highly correlated with the difference. Finally, pathway enrichment analysis indicated that disorders of metabolic pathways, such as tryptophan metabolism, steroid hormone biosynthesis, and ferroptosis(linoleic acid metabolism and arachidonic acid metabolism), may be the potential mechanism of the difference. Liver injury induced by dictamnine is significantly different between males and females, which may be caused by the disorders of tryptophan metabolism, steroid hormone biosynthesis, and ferroptosis pathways.

Study on the protective effect of Hypericum perforatum on cerebral ischemia-reperfusion injury in rats and its mechanism / 中国药房

OBJECTIVE To study the protective effect and potential mechanism of Hypericum perforatum on cerebral ischemia- reperfusion in rats. METHODS The male SD rats were randomly divided into sham operation group， model group， positive control group （nimodipine 0.012 g/kg）， H. perforatum high-dose and low-dose groups （5.212， 1.303 g/kg）， with 10 rats in each group. Except for sham operation group， the left middle cerebral artery ischemia-reperfusion model was established with the modified suture method. Administration groups were given relevant medicine intragastrically since the second day after surgery， once a day， for 7 consecutive days. The neurological function scores of rats were measured before drug intervention （the first day after modeling） and after the last administration， and the cerebral infarction after the last administration was observed using TTC staining method；HE staining and TUNEL staining methods were used to observe the pathological changes of the cerebral cortex and hippocampus， and the apoptosis of nerve cells， respectively. Western blot and RT-PCR were used to observe the protein and mRNA expressions of erythropoietin （EPO）， erythropoietin receptor （EPOR）， Janus kinase 2 （JAK2） and signal transduction and activator of transcription 3 （STAT3）， and protein expression of phosphorylated STAT3 （p-STAT3）， respectively. RESULTS Compared with sham operation group， neurological function score and the proportion of cerebral infarction in model group were significantly increased before intervention and after the last administration （P＜0.01）， with significant damage to nerve cells in cerebral cortex and hippocampus， an increase in apoptotic nerve cells， and a significant increase in apoptosis rate （P＜0.01）； protein and mRNA expressions of EPO and EPOR in the brain tissue were significantly reduced （P＜0.01）， while the protein expressions of JAK2， p- STAT3 and STAT3， and mRNA expressions of JAK2 and STAT3 were significantly increased （P＜0.01）. Compared with model group， the damage and apoptosis of nerve cells in cerebral cortex and hippocampus of rats in administration groups were improved， and the quantitative indicators were almost significantly improved （P＜0.05 or P＜0.01）. CONCLUSIONS H. perforatum has a protective effect against cerebral ischemia-reperfusion injury in rats， and the related mechanism may be related to the regulation of EPO-mediated JAK2/STAT3 signaling pathway.

Treatment responses, outcomes, and prognostic factors associated with them in patients with secondary acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate treatment responses, outcomes, and prognostic factors in adults with secondary acute myeloid leukemia (sAML) . Methods: Between January 2008 and February 2021, date of consecutive cases of younger than 65 years of adults with sAML were assessed retrospectively. Clinical characteristics at diagnosis, treatment responses, recurrence, and survival were evaluated. Logistic regression and Cox proportional hazards model were employed to determine significant prognostic indicators for treatment response and survival. Results: 155 patients were recruited, including 38, 46, 57, 14 patients belonging to t-AML, and AML with unexplained cytopenia, post-MDS-AML, and post-MPN-AML, respectively. In the 152 evaluable patients, the rate of MLFS after the initial induction regimen was 47.4%, 57.9%, 54.3%, 40.0%, and 23.1% in the four groups (P=0.076) . The total rate of MLFS after the induction regimen was 63.8%, 73.3%, 69.6%, 58.2%, and 38.5% (P=0.084) , respectively. Multivariate analysis demonstrated that male gender (OR=0.4, 95% CI 0.2-0.9, P=0.038 and OR=0.3, 95% CI 0.1-0.8, P=0.015) , SWOG cytogenetic classification into unfavorable or intermediate (OR=0.1, 95% CI 0.1-0.6, P=0.014 and OR=0.1, 95% CI 0.1-0.3, P=0.004) and receiving low-intensity regimen as induction regimen (OR=0.1, 95% CI 0.1-0.3, P=0.003 and OR=0.1, 95%CI 0.1-0.2, P=0.001) were typical adverse factors impacting the first CR and the final CR; PLT<45 × 10(9)/L (OR=0.4, 95%CI 0.2-0.9, P=0.038) and LDH ≥258 U/L (OR=0.3, 95%CI 0.1-0.7, P=0.005) were independent factors for CR. Among the 94 patients with achieving MLFS, 46 cases had allogeneic hematopoietic stem cell transplantation. With a median follow-up period of 18.6 months, the probabilities of relapse-free survival (RFS) and overall survival (OS) at 3 years were 25.4% and 37.3% in patients with transplantation, and in patients with chemotherapy, the probabilities of RFS and OS at 3-year were 58.2% and 64.3%, respectively. At the time of achieving MLFS, multivariate analysis revealed that age ≥46 years (HR=3.4, 95%CI 1.6-7.2, P=0.002 and HR=2.5, 95%CI 1.1-6.0, P=0.037) , peripheral blasts ≥17.5% at diagnosis (HR=2.5, 95%CI 1.2-4.9, P=0.010 and HR=4.1, 95%CI 1.7-9.7, P=0.002) , monosomal karyotypes (HR=4.9, 95%CI 1.2-19.9, P=0.027 and HR=28.3, 95%CI 4.2-189.5, P=0.001) were typical adverse factors influencing RFS and OS. Furthermore, CR after induction chemotherapy (HR=0.4, 95%CI 0.2-0.8, P=0.015) and transplantation (HR=0.4, 95%CI 0.2-0.9, P=0.028) were substantially linked to longer RFS. Conclusion: Post-MDS-AML and post-MPN-AML had lower response rates and poorer prognoses than t-AML and AML with unexplained cytopenia. In adults with male gender, low platelet count, high LDH, and SWOG cytogenetic classification into unfavorable or intermediate at diagnosis, and receiving low-intensity regimen as the induction regimen predicted a low response rate. Age ≥46 years, a higher proportion of peripheral blasts and monosomal karyotype had a negative effect on the overall outcome. Transplantation and CR after induction chemotherapy were greatly linked to longer RFS.

A scoring system to predict molecular responses in patients with chronic myeloid leukemia in the chronic phase receiving initial imatinib therapy / 中华血液学杂志

Objective: To develop a scoring system to predict molecular responses in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving initial imatinib therapy. Methods: Data from consecutive adults with newly diagnosed CML-CP treated by initial imatinib was interrogated and subjects were distributed randomly into training and validation cohort, in a ratio of 2∶1. Fine-gray models were applied in the training cohort to identify co-variates of predictive value for major molecular response (MMR) and MR4. A predictive system was built using significant co-variates. The predictive system was then tested in the validation cohort and the area under the receiver-operator characteristic curve (AUROC) was used to estimate accuracy of the predictive system. Results: 1 364 CML-CP subjects receiving initial imatinib were included in this study. Subjects were distributed randomly into training cohort (n=909) and validation cohort (n=455) . In the training cohort, the male gender, European Treatment and Outcome Study for CML (EUTOS) Long-Term Survival (ELTS) intermediate-risk, ELTS high-risk, high WBC (≥130×10(9)/L or 120×10(9)/L, MMR or MR4) and low HGB (<110 g/L) at diagnosis were significantly related with poor molecular responses and were given points based on their regression coefficients. For MMR, male gender, ELTS intermediate-risk and low HGB (<110 g/L) were given 1 point; ELTS high-risk and high WBC (≥130×10(9)/L) , 2 points. For MR4, male gender was given 1 point; ELTS intermediate-risk and low HGB (<110 g/L) were given 2 points; high WBC (≥120×10(9)/L) , 3 points; ELTS high-risk, 4 points. We divided all subjects into 3 risk subgroups according to the predictive system above. Cumulative incidence of achieving MMR and MR4 in 3 risk subgroups was significantly different in both training and validation cohort (all P values <0.001) . In the training and validation cohorts, the time-dependent AUROC ranges of MMR and MR4 predictive systems were 0.70-0.84 and 0.64-0.81, respectively. Conclusions: A scoring system combining gender, WBC, HGB level and ELTS risk was built to predict MMR and MR4 in CML-CP patients receiving initial imatinib therapy. This system had good discrimination and accuracy, which could help phsicians optimize the selsction of initial TKI-therapy.

Efficacy and safety of parecoxib versus ketorolac tromethamine for perioperative analgesia：a systematic review / 中国药房

OBJECTIVE To compare the efficacy and safety of parecoxib and ketorolac tromethamine for perioperative analgesia， and to provide evidence-based reference for clinical drug use. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， VIP， Wanfang Data， Baidu and Google， randomized controlled trials （RCT） about parecoxib （trial group） versus ketorolac tromethamine （control group） for perioperative analgesia were collected from the inception to Jun. 17th， 2022. After screening the literature and extracting the data， the quality of the included literature was evaluated using the bias risk assessment tool recommended by Cochrane system evaluator manual 5.1.0. Meta-analysis， sensitivity analysis and publication bias analysis were performed with RevMan 5.4 software. RESULTS A total of 12 RCTs were included， with 1 118 patients. Meta- analysis results showed that at the time of administration before anesthesia induction， there was no statistically significant difference between the 2 groups in visual analogue scale （VAS） [MD＝－0.16， 95%CI （－0.41， 0.09）， P＝0.20]， numerical rating scale （NRS） [MD＝0.01， 95%CI （－0.36， 0.38）， P＝0.97]， postoperative bleeding [MD＝0.15， 95%CI （－0.63， 0.93）， P＝0.71]， and consumption of opioid analgesics [MD＝0.12， 95%CI （－0.77， 1.01）， P＝0.79]. At the time of postoperative administration， VAS and bleeding volume at 48 h after operation of trial group were significantly lower than control group （P＜0.05）. The results of subgroup analysis by different com assessment time points showed that the VAS of patients in trial group at 0 h after operation were significantly lower than control group at the time of administration before anesthesia induction； at the time of postoperative administration， VAS of patients in the trial group at 12 h and 48 h after operation were significantly lower than control group （P＜0.05）. There was no statistical significance in the incidence of ADR between 2 groups [RR＝0.93，95%CI （0.78，1.11），P＝0.43]. The results of subgroup analysis according to different types of adverse reactions showed that the incidence of nausea and vomiting of trial group was significantly lower than control group， and the incidence of other adverse reactions was significantly higher than control group （P＜0.05）. Results of sensitivity analysis showed that study results were stable and reliable. Results of publication bias analysis showed that there was great possibility of publication bias in this study. CONCLUSIONS The efficacy of parecoxib is equivalent to that of ketorolac tromethamine for perioperative analgesia before operation； at the time of administration after operation， parecoxib has better analgesic effect and less postoperative bleeding； the incidence of nausea and vomiting caused by parecoxib is lower at any time of administration.

Factors influencing severe cytopenia in chronic phase chronic myeloid leukemia patients receiving initial second generation tyrosine kinase inhibitors and its impact on treatment responses and outcomes / 中华血液学杂志

Objective: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving initial second-generation tyrosine kinase inhibitors (2G-TKI) . Methods: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. Results: Data from 267 patients who received initial 2G-TKI, including nilotinib (n=239, 89.5% ) and dasatinib (n=28, 10.5% ) , were interrogated. The median age was 36 (range, 18-73) years, and 156 (58.4% ) patients were male. At a median treatment period of 1.0 (0.1-3.0) month, 43 (16.1% ) patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0 (0.1-24.6) month. Male (OR=2.9, 95% CI 1.2-6.8; P=0.018) , age of ≥36 years (OR=3.2, 95% CI 1.4-7.2, P=0.005) , a spleen below a costal margin of ≥7 cm (OR=2.8, 95% CI 1.2-6.6, P=0.020) , and a hemoglobin (HGB) level of <100 g/L (OR=2.9, 95% CI 1.3-6.8, P=0.012) at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups (P < 0.001) . Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response (CCyR, HR=0.5, 95% CI 0.3-0.7, P<0.001) and major molecular response (MMR, HR=0.4, 95% CI 0.3-0.8, P=0.004) and was not significantly associated with failure, progression, and survival. Conclusion: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.

Analysis of the characteristics of primary acute myeloid leukemia with 11q23/KMT2A rearrangements in ninety patients / 中华医学遗传学杂志

OBJECTIVE@#To investigate the clinical and prognostic characteristics of primary acute myeloid leukemia (AML) with 11q23/KMT2A rearrangements.@*METHODS@#Clinical data of 90 patients with primary AML and 11q23/KMT2A rearrangements were analyzed retrospectively.@*RESULTS@#By karyotyping analysis, 80 of the 90 patients had translocations involving 11q23/KMT2A, with t(9;11)(p22;q23), t(6;11)(q27;q23), t(10;11)(p12;q23) and t(11;19)(q23;p13) being the most common ones, while 10 cases were found to have non-translocation abnormalities. The overall complete remission (CR) rate was 75.6%, and patients with t(6;11) had lower CR rate compared with non-t(6;11) patients (47.1% vs. 82.2%, P = 0.005). After a median follow-up of 24.5 months, the patients receiving allo-hematopoietic stem cell transplantation (allo-HSCT) had significantly higher 3-year overall survival (OS) (80.3% vs. 16.6%, P < 0.001) and 3-year event-free survival (EFS) (73.5% vs. 16.3%, P < 0.001) compared with non-transplant patients. Patients with t(6;11) had the lowest 3-year OS (11.8% vs. 56.0%, P < 0.001) and 3-year EFS (5.9% vs. 53.8%, P < 0.001) compared with other type of abnormalities. No significant difference was noted in the survival between patients with t(9;11) and non-t(9;11) regardless whether they had received HSCT.@*CONCLUSION@#The clinical characteristics of primary AML with 11q23/KMT2A rearrangements are heterogeneous. Patients did not receive HSCT had poorer survival, particularly with the presence of t(6;11). Allo-HSCT could significantly improve the survival of such patients.

Comparison of BCR::ABL (P210) mRNA levels detected by dPCR and qPCR methods in patients with chronic myeloid leukemia / 中华血液学杂志

Objective: To compare digital polymerase chain reaction (dPCR) and real-time quantitative PCR (qPCR) measurements of BCR::ABL (P210) mRNA expression in patients with chronic myeloid leukemia (CML) . Methods: In this non-interventional, cross-sectional study, BCR::ABL (P210) mRNA was simultaneously measured by dPCR and qPCR in peripheral blood samples collected from patients with CML who underwent tyrosine kinase inhibitor therapy and who achieved at least a complete cytogenetic response from September 2021 to February 2023 at Peking University People's Hospital. The difference, correlation, and agreement between the two methods were evaluated using the Wilcoxon signed-rank test, Spearman's correlation, and Bland-Altman analysis, respectively. Results: In total, 459 data pairs for BCR::ABL mRNA expression measured by dPCR and qPCR from 356 patients with CML were analyzed. There was a significant difference in BCR::ABL mRNA expression between the two methods (P<0.001). When analyzed by the depth of the molecular response (MR), a significant difference only existed for patients with ≥MR4.5 (P<0.001). No significant difference was observed for those who did not achieve a major MR (no MMR; P=0.922) or for those who achieved a major MR (MMR; P=0.723) or MR4 (P=0.099). There was a moderate correlation between the BCR::ABL mRNA expression between the two methods (r=0.761, P<0.001). However, the correlation gradually weakened or disappeared as the depth of the MR increased (no MMR: r=0.929, P<0.001; MMR: r=0.815, P<0.001; MR4: r=0.408, P<0.001; MR4.5: r=0.176, P=0.176). In addition, the agreement in BCR::ABL mRNA expression between the two methods in those with MR4.5 was weaker than other groups (no MMR: ▉= 0.042, P=0.846; MMR:▉=0.054, P=0.229; MR4:▉=-0.020, P=0.399; MR4.5:▉=-0.219, P<0.001) . Conclusions: dPCR is more accurate than qPCR for measuring BCR::ABL (P210) mRNA expression in patients with CML who achieve a stable deep MR.

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Optimization of quality assessment system of clinical blood transfusion records / 中国输血杂志

【Objective】 To determine the value of quality assessment system in supervising standard clinical blood use and improving the quality of clinical blood transfusion medical records. 【Methods】 The clinical blood transfusion records of Children′s Hospital, Zhejiang University School of Medical every quarter from January 2019 to December 2022 were selected and extracted for evaluation by 5% to 10% for the current season. These blood transfusion medical records were scored and graded A(≥90 points)/B(80-89 points)/C(<80 points)according to the Evaluation Table of Clinical Science Rational Use of Blood in Children′s Hospital of Zhejiang University, and the annual A rate was statistically analyzed. After summarizing the deduction points, a rectification plan was submitted to the medical department and publicized on the hospital network. 【Results】 A total of 1 975 blood transfusion medical records were analyzed from January 2019 to December 2022, including 343 in 2019 (17.37%), 517 in 2020 (26.18%), 556 in 2021 (28.15%) and 559 in 2022 (28.30%), with Grade A rates at 67.06%, 92.07%, 93.17% and 91.06%, respectively. According to Pearson Chi-square test, the Grade A rates of blood transfusion records in 2020, 2021 and 2022 were significantly higher than those in 2019 (P<0.000 1). In the assessment, the main reasons for deduction of points were missed pre-transfusion immunization tests and missed blood transfusion course records. From 2019 to 2022, the missed rates of pre-transfusion immunization tests were 22.68%, 6.47%, 1.26% and 2.49%, and the missed rates of blood transfusion course records were 32.21%, 10.59%, 5.57% and 6.61%, respectively. 【Conclusion】 The regular and reasonable assessment and publicity system of blood transfusion medical records is conducive to improving the quality of blood transfusion medical records, promoting rational blood use and ensuring the safety of blood use for children.

Combination of socio-demographic and clinical co-variates for predicting treatment responses and outcomes in patients with chronic myeloid leukemia in the chronic phase / 中华血液学杂志

Objective: To explore the impacts of socio-demographic and clinical co-variates on treatment responses and outcomes in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving tyrosine kinase inhibitor (TKI) and identified the predictive models for them. Methods: Data of newly diagnosed adult patients with CML-CP receiving first-line TKI and having complete socio-demographic data and clinical information were reviewed. Cox model was used to identify the independent variables associated with complete cytogenetic response (CCyR) , major molecular response (MMR) , molecular response 4 (MR(4)) and molecular response 4.5 (MR(4.5)) , as well as failure-free survival (FFS) , progression-free survival (PFS) , overall survival (OS) and CML-related OS. Results: A total of 1414 CML-CP patients treated with first-line imatinib (n=1176) , nilotinib (n=170) or dasatinib (n=68) were reviewed. Median age was 40 (18-83) years and 873 patients (61.7% ) were males. Result of the multivariate analysis showed that lower educational level (P<0.001-0.070) and EUTOS long-term survival intermediate or high-risk (P<0.001-0.009) were significantly associated with lower cumulative incidences of CCyR, MMR, MR(4) and MR(4.5), as well as the inferior FFS, PFS, OS and CML-related OS. In addition, those who were males, from rural households, had white blood cells (WBC) ≥120×10(9)/L, hemoglobin (HGB) <115 g/L and treated with first-line imatinib had significantly lower cumulative incidences of cytogenetic and/or molecular responses. Being single, divorced or widowed, having, rural household registration, WBC≥120×10(9)/L, HGB<15 g/L, and comorbidity (ies) was significantly associated with inferior FFS, PFS, OS, and/or CML-related OS. Thereafter, the patients were classified into several subgroups using the socio-demographic characteristics and clinical variables by cytogenetic and molecular responses, treatment failure and disease progression, as well as overall survival and CML-related OS, respectively. There were significant differences in treatment responses and outcomes among the subgroups (P<0.001) . Conclusion: Except for clinical co-variates, socio-demographic co-variates significantly correlated with TKI treatment responses and outcomes in CML-CP patients. Models established by the combination of independent socio-demographic and clinical co-variates could effectively predict the responses and outcome.

Species Differences of Bakuchiol-induced Liver Injury in Mice Based on Transcriptomics / 中国实验方剂学杂志

ObjectiveTo explore the differences in response to bakuchiol-induced hepatotoxicity between Institute of Cancer Research （ICR） mice and Kunming （KM） mice. MethodThe objective manifestations of bakuchiol-induced hepatotoxicity in mice were confirmed by acute and subacute toxicity animal experiments， and enrichment pathways of differential genes between normal ICR mice and KM mice were compared by transcriptomics. The real-time quantitative polymerase chain reaction （real-time qPCR） assay was used to verify the mRNA expression of key genes in the related pathways to confirm the species differences of bakuchiol-induced liver injury. ResultIn the subacute toxicity experiment， compared with the normal mice， the ICR mice showed increased serum content of alkaline phosphatase （ALP）， and 5′-nucleotidase （5′-NT）， without significant difference， and no manifest change was observed in KM mice. Pathological results showed that hepatocyte hypertrophy was the main pathological feature in ICR mice and hepatocyte steatosis in KM mice. In the acute toxicity experiment， KM mice showed erect hair， mental malaise， and near-death 3 days after administration. The levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in KM mice （400 mg·kg-1） significantly increased（P<0.01）， and the activity of total reactive oxygen species （SOD） in liver significantly decreased（P<0.01）compared with those in normal mice， while the serum content of 5′-NT and cholinesterase （CHE） in ICR mice （400 mg·kg-1） were significantly elevated （P<0.01）. The liver/brain ratio in ICR mice increased by 20.34% and that in KM mice increased by 29.14% （P<0.01）. The main pathological manifestation of the liver in ICR mice was hepatocyte hypertrophy， while those in KM mice were focal inflammation， hepatocyte hypertrophy， and hepatocyte steatosis. Kyoto Encyclopedia of Genes and Genomes（KEGG）and Reactome pathway enrichment analyses showed that the differential gene expression between ICR mice and KM mice was mainly involved in oxidative phosphorylation， bile secretion， bile acid and bile salts synthesis， and metabolism pathway. CYP7A1 was up-regulated in all groups with drug intervention （P<0.01） and MRP2 was reduced in all groups with drug intervention of KM mice （P<0.01） and elevated in all groups with drug intervention of ICR mice （P<0.01） compared with those in the normal group. The expression of BSEP was lowered in ICR mice with acute liver injury （400 mg·kg-1） （P<0.05）. SHP1 was highly expressed in KM mice with acute liver injury （400 mg·kg-1）. The expression of FXR was diminished in ICR mice with subacute liver injury （200 mg·kg-1） （P<0.01）. SOD1， CAT， and NFR2 significantly decreased in KM mice with acute liver injury （400 mg·kg-1）， and CAT dwindled in KM mice with subacute liver injury （200 mg·kg-1） （P<0.01）. GSTA1 and GPX1 significantly increased in KM mice with acute liver injury （400 mg·kg-1） （P<0.01） and SOD1， CAT， NRF2， and GSTA1 significantly increased in ICR mice with subacute liver injury （200 mg·kg-1） （P<0.01）. CAT and NRF2 significantly increased in ICR mice with acute liver injury （400 mg·kg-1） （P<0.01）. ConclusionWith the increase in the dosage of bakuchiol， the liver injury induced by oxidative stress in KM mice was gradually aggravated， and ICR mice showed stronger antioxidant capacity. The comparison of responses to bakuchiol-induced hepatotoxicity between ICR mice and KM mice reveals that ICR mice are more suitable for the investigation of the mechanisms related to bile secretion and bile acid metabolism in the research on bakuchiol-induced hepatotoxicity in mice. KM mice are more prone to liver injury caused by oxidative stress.

Dermoscopic characteistics of trichoblastoma: a preliminary investigation / 中华皮肤科杂志

Objective:To preliminarily investigate dermoscopic characteristics of trichoblastoma, and to provide ideas for clinical diagnosis of trichoblastoma.Methods:Clinical data were collected from 5 patients with trichoblastoma who underwent both dermoscopic and histopathological examinations in Wuhan No.1 Hospital from November 2018 to July 2021, and dermoscopic features were analyzed retrospectively.Results:According to the presence or absence of pigments, trichoblastoma was divided into 2 subtypes: pigmented trichoblastoma (3 cases) and non-pigmented trichoblastoma (2 cases) . Dermoscopic examination of the 3 cases of pigmented trichoblastoma showed blue-gray ovoid nests (3 cases) , arborizing vessels (2 cases) , blue-gray globules (2 cases) , bright white structureless areas (2 cases) , concentric structures (1 case) and ulcers (1 case) ; no yellow-whitish homogenous structure was found. As for non-pigmented trichoblastoma, dermoscopic features included arborizing vessels (2 cases) , yellow-whitish homogenous structures (2 cases) , bright white structureless areas (2 cases) and blue-gray globules (1 case) ; no ulcers or blue-gray ovoid nests were observed in either case.Conclusion:Dermoscopic patterns differ between pigmented and non-pigmented trichoblastoma, so dermoscopy can provide preliminary diagnostic clues for trichoblastoma.

Research progress on the role of autophagy pathway in acute renal injury and targeted treatment strategies / 中国综合临床

Autophagy is a highly conserved intracellular catabolic process used to degrade cytoplasmic components. In recent years, it has attracted much attention because of its importance in the pathogenesis and targeted therapy of acute and chronic kidney disease. Autophagy plays an important role in maintaining renal homeostasis under physiological and pathological conditions. The study of conditional autophagy related gene knockout specific to various renal cells has gradually revealed the role of autophagy in renal diseases. Recent studies have found that autophagy deficiency may play a key role in different pathological states of the kidney. Activated autophagy shows cytoprotective function in both glomerulus and renal tubulointerstitium, suggesting that the up regulation of autophagy may become a potential therapeutic strategy. However, there is also contrary evidence that autophagy may be harmful, which poses a great challenge to the development of therapeutic strategies for up-regulated autophagy.

Analysis and practice on the " dual-channel" management mode of national medicare negotiated drugs in China / 中华医院管理杂志

" Dual-channel" management is an important management measure to solve the difficulty of national medicare negotiated drugs entering the hospital and improve the accessibility of the drugs. China clearly included some social pharmacies into the supply guarantee channel of national medicare negotiated drugs, and formed a " dual-channel" supply mode for negotiated drugs together with the hospital supply. By sorting out China′s national medicare negotiated drugs policy management documents and the management modes and specific measures in various regions and periods, this paper summarized and analyzed the progress of process management, multi-level medical security integration, remote handling, drug safety supervision, and information construction in various regions. Based on the relevant policy guidance and local practical experience, the authors explored and optimized the " dual-channel" landing management, so as to provide reference and suggestions for further improving the accessibility of national medicare negotiated drugs and giving full play to the effectiveness of medical security.