Objective:To investigate the clinical characteristics and prognosis of single center adult chronic myeloid leukemia in chronic phase(CML-CP).Methods:Clinical data of 41 adult CML-CP patients in Department of Hematology,Shanghai Fengxian District Central Hospital from January 2015 to May 2021 were retrospectively analyzed.The clinical characteristics and prognosis of patients between＜60 years group and ≥ 60 years group were compared.Results:The 41 patients included 27(65.9％)males and 14(34.1％)females.The median age of the patients was 56(19-84)years,with 22 cases(53.7％)＜60 years and 19 cases(46.3％)≥60 years.Univariate analysis indicated that the proportions of patients with comorbidities,intermediate/high-risk Sokal score,myelofibrosis,and lactate dehydrogenase ≥1 000 U/L were significantly increased in ≥60 years group compared with＜60 years group at initial diagnosis(all P＜0.05).There were no statistical differences in the distribution of sex,ELST score,white blood cell count,platelet count,peripheral blood basophil percentage,peripheral blood eosinophil percentage and bone marrow primitive cell percentage between the two groups(P＞0.05).The proportion of patients taking reduced-dose imatinib in≥60 years group significantly increased(P＜0.001).Patients＜60 years had a higher proportion of molecular biological remission after treatment of tyrosine kinase inhibitors(TKIs)than patients ≥ 60 years(P＜0.001).The incidence of non-hematologic adverse reactions to TKI therapy significantly increased in patients ≥ 60 years(P＜0.001).Multivariate analysis showed that no adverse factors affecting the efficacy and prognosis of TKI.Conclusion:Compared with adult CML-CP patients＜60 years,patients ≥ 60 years gain fewer benefits from TKI treatment and increased adverse reactions.

Objective:To explore the value of REG3α,sST2 and TNFR1 in peripheral blood for risk stratification and prognostic evaluation of acute graft-versus-host disease(aGVHD)after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in children.Methods:From January 2020 to March 2022,70 children with aGVHD after allo-HSCT in the First Affiliated Hospital of Zhengzhou University were selected as the research objects,of which 50 cases were mild aGVHD(grade Ⅰ-Ⅱ)and 20 cases were severe aGVHD(grade Ⅲ-Ⅳ).30 healthy children who underwent physical examinations in our hospital during the same period were selected as the control group.Luminex platform was used to detect the protein expression levels of REG3α,sST2 and TNFR1 during aGVHD occurrence,and the differences between the three groups were analyzed by one-way ANOVA.According to the outcome of aGVHD treatment within 28 days,the patients were divided into a good prognosis group of 58 cases and a poor prognosis group of 12 cases.The ROC curve was used to analyze the value of REG3α,sST2 and TNFR1 in predicting the prognosis of children with aGVHD.Results:The peripheral blood levels of REG3α,sST2 and TNFR1 in the mild aGVHD and severe aGVHD groups were significantly higher than those in the control group(P＜0.05),and those in the severe aGVHD group were significantly higher than those in the mild aGVHD group(P＜0.05).Compared with the good prognosis group,the peripheral blood levels of REG3α,sST2 and TNFR1 in the poor prognosis group were significantly higher(t=9.27,3.33,2.97;P＜0.01).ROC curve analysis showed that the area under the curve(AUC),sensitivity and specificity of the combined detection of REG3α,sST2 and TNFR1 in predicting the prognosis of children with aGVHD were higher than those of the above indicators detected alone or in pairs.Conclusion:The expression levels of REG3α,sST2 and TNFR1 were related to the severity of aGVHD.The combination of REG3α,sST2 and TNFR1 has a high clinical value in predicting the prognosis of children with aGVHD,which is expected to provide a reliable reference for clinical evaluation of the prognosis of children with aGVHD.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

This study aimed to investigate the potential role of Colquhounia Root Tablets against bone destruction in rheumatoid arthritis(RA) and its molecular mechanism. The study used ultra-performance liquid chromatography-mass spectrometry to analyze the major components of Colquhounia Root Tablets and predicted its candidate target gene set based on the major components. The key targets of RA bone destruction were obtained through GeneCards and the Database of Genetics and Medical Literature(OMIM), protein-protein interaction(PPI) network was constructed, and the key targets were identified by topological analysis. The molecular mechanism of Colquhounia Root Tablets against RA bone destruction was further revealed using Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. The effects of Colquhounia Root Tablets on macrophage viability was assessed by MTS assay and screened for non-toxic concentrations. A model of receptor activator of nuclear factor-κB(RANKL) induced osteoclast differentiation in vitro was constructed. Colquhounia Root Tablets were used to observe the formation and differentiation of osteoclasts by tartrate-resistant acid phosphatase(TRAP) staining and fibrous actin(F-actin) staining, and the effects of Colquhounia Root Tablets on the changes of core target proteins in the osteoclast differentiation system were detected by immunofluorescence and Western blot. The results showed that the main components of Colquhounia Root Tablets included 14 compounds such as triptolide, celastrol, and triptophenolide. Further network analysis revealed that heat-shock protein 90(HSP90) was the key target gene of Colquhounia Root Tablets for anti-RA bone destruction. TRAP staining and F-actin staining showed that the number and area of TRAP-positive polymorphonuclear cells, as well as actin rings, were reduced in a dose-dependent manner after the intervention of Colquhounia Root Tablets(P<0.01). Western blot results showed that the expression of HSP90 protein was significantly reduced after intervention with Colquhounia Root Tablets at 20 and 40 μg·mL~(-1)(P<0.01); Colquhounia Root Tablets at 10 μg·mL~(-1) could significantly decrease the expression of necrosis factor receptor associated molecule 6(TRAF6) and nuclear factor of activated T cells 1(NFATc1) proteins(P<0.01); moreover, all doses of Colquhounia Root Tablets significantly reduced the expression of osteoclast differentiation marker proteins matrix metalloproteinase 9(MMP9) and cathepsin K(CTSK)(P<0.01).Immunofluorescence results further confirmed that Colquhounia Root Tablets significantly inhibited HSP90 and CTSK levels, as well as NFATc1 activation in osteoblasts. In conclusion, the present study confirmed that Colquhounia Root Tablets may inhibit RANKL-induced osteoclast differentiation by regulating the key target of HSP90, thus exerting an anti-RA bone destruction effect, which will provide a new idea for Colquhounia Root Tablets to prevent and treat bone destruction in rheumatoid arthritis.
Osteoclasts/metabolism* ; Mice ; Animals ; Cell Differentiation/drug effects* ; HSP90 Heat-Shock Proteins/genetics* ; Drugs, Chinese Herbal/chemistry* ; Plant Roots/chemistry* ; Humans ; Arthritis, Rheumatoid/physiopathology* ; Protein Interaction Maps/drug effects*

Objective: To evaluate different methods' efficacy of controlling acute bleeding and managing long-term menstruation in patients with heavy menstrual bleeding (HMB) associated with antithrombotic therapy. Methods: The clinical data of 22 cases with HMB associated with antithrombotic therapy admitted to Peking University People's Hospital from January 2010 to August 2022 were analyzed, aged 39 years old (26-46 years). Changes in menstrual volume, hemoglobin (Hb), and quality of life were collected after control of acute bleeding and long-term menstrual management. Menstrual volume was assessed by pictorial blood assessment chart (PBAC), and quality of life was assessed by menorrhagia multi-attribute scale (MMAS). Results: (1) Treatment of acute bleeding: of the 22 cases with HMB associated with antithrombotic therapy, 16 cases were treated in our hospital and 6 in other hospital for emergency bleeding; of the 16 cases treated in our hospital, 3 underwent emergency intrauterine Foley catheter balloon compression due to severe bleeding (Hb decreased by 20 to 40 g/L within 12 hours). Of the 22 cases with antithrombotic therapy-related HMB, 15 (including 2 cases with severe bleeding) underwent emergency aspiration or endometrial resection, and intraoperative placement of levonorgestrel-releasing intrauterine system (LNG-IUS) followed by a significant reduction in bleeding volume; 3 cases had controlled acute bleeding after rivaroxaban dose reduction and continued observation; 2 cases were given gonadotropin-releasing hormone agonists to control acute bleeding in other hospital, of which 1 case was temporarily treated with periodic blood transfusion, and the other one patient underwent total hysterectomy; and 2 cases had temporary amenorrhea with oral mifepristone after intrauterine balloon compression or oral norethindrone. (2) Long-term menstrual management: of the 22 cases with antithrombotic therapy-related HMB, 15 had LNG-IUS placement and 12 had LNG-IUS placement for 6 months, and menstrual volume was significantly reduced [PBAC scores were 365.0 (272.5-460.0) vs 25.0 (12.5-37.5), respectively; Z=4.593, P<0.001], Hb was significantly increased [91.5 g/L (71.8-108.2 g/L) vs 128.5 g/L (121.2-142.5 g/L); Z=4.695, P<0.001], and quality of life was significantly improved [MMAS scores were 415.0 (327.5-472.5) vs 580.0 (570.0-580.0), respectively; Z=-3.062, P=0.002] before placement compared with 6 months after placement. Three rivaroxaban dose reduction patients' PBAC scores decreased by 20 to 35 but remained >100, and perceived quality of life did not change significantly. Two cases with temporary amenorrhea treated with oral mifepristone felt significantly improved quality of life, and the MMAS scores increased by 220 and 180, respectively. Conclusion: Intrauterine Foley catheter balloon compression, aspiration or endometrial ablation could be used to control acute bleeding in patients with antithrombotic therapy-related HMB, and LNG-IUS for long-term management could reduce menstrual volume, increase hemoglobin, and improve the quality of life of patients.
Female ; Humans ; Adult ; Menorrhagia/etiology* ; Fibrinolytic Agents/adverse effects* ; Levonorgestrel/adverse effects* ; Amenorrhea/drug therapy* ; Mifepristone/therapeutic use* ; Quality of Life ; Rivaroxaban/therapeutic use* ; Hemoglobins ; Intrauterine Devices, Medicated/adverse effects* ; Contraceptive Agents, Female

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.

Growing clinical evidence shows that Qufeng Gutong Cataplasm may exert a significant analgesic effect. However, the pharmacological characteristics and mechanisms underlying this prescription are still unclear. In the current study, a "disease-syndrome-symptom-formula" association network analysis was performed to explore the pharmacological characteristics and mechanisms of Qufeng Gutong Cataplasm against osteoarthritis (OA), neuropathic pain (NP), chronic inflammatory pain (CIP) and myofascial pain syndrome (MPS) by integrating clinical phenomics data, transcriptomics data and biological interaction network mining. As a result, the three functional modules (Qufeng Sanhan-QFSHG, Shujin Huoxue-SJHXG and Xiaozhong Zhitong-XZZTG) enriched by the drug network targets were all related to the pharmacological effects of Qufeng Gutong Cataplasm, including dispersing cold and relieving pain, activating blood and relieving pain, reducing swelling and relieving pain. In addition, the main pharmacological effects of QFSHG and XZZTG were dispelling wind and dispersing cold and dehumidifying, promoting Qi and reducing swelling and relieving pain, respectively. In terms of reversing the imbalance of "immune-inflammation-vascular axis", the main pharmacological effects of SJHXG were regulating the liver and promoting Qi, activating blood circulation and removing stasis. Mechanically, the key network targets of Qufeng Gutong Cataplasm against OA, NP, CIP and MPS may play a therapeutic role in relieving hyperalgesia and paresthesia by reversing the "neuro-endocrine-immune" imbalance system during the occurrence and progression of diseases. In conclusion, our data indicate that Qufeng Gutong Cataplasm may relieve the pain and wind-cold-dampness arthralgia syndrome related symptoms by regulating the "neuro-endocrine-immune" system, neurological and endocrine disorders and reversing the imbalance of "immunity-inflammation". The relevant results may provide a network-based evidence for clinical positioning of Qufeng Gutong Cataplasm, and offer a direction for further clinical and experimental validation.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

The present study investigated the mechanism of artesunate in the treatment of bone destruction in experimental rheumatoid arthritis(RA) based on transcriptomics and network pharmacology. The transcriptome sequencing data of artesunate in the inhibition of osteoclast differentiation were analyzed to obtain differentially expressed genes(DEGs). GraphPad Prism 8 software was used to plot volcano maps and heat maps were plotted through the website of bioinformatics. GeneCards and OMIM were used to collect information on key targets of bone destruction in RA. The DEGs of artesunate in inhibiting osteoclast differentiation and key target genes of bone destruction in RA were intersected by the Venny 2.1.0 platform, and the intersection target genes were analyzed by Gene Ontology(GO)/Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment. Finally, the receptor activator of nuclear factor-κB(RANKL)-induced osteoclast differentiation model and collagen-induced arthritis(CIA) model were established. Quantitative real time polymerase chain reaction(q-PCR), immunofluorescence, and immunohistochemistry were used to verify the pharmacological effect and molecular mechanism of artesunate in the treatment of bone destruction in RA. In this study, the RANKL-induced osteoclast differentiation model in vitro was established and intervened with artesunate, and transcriptome sequencing data were analyzed to obtain 744 DEGs of artesunate in inhibiting osteoclast differentiation. A total of 1 291 major target genes of bone destruction in RA were obtained from GeneCards and OMIM. The target genes of artesunate in inhibiting osteoclast differentiation and the target genes of bone destruction in RA were intersected to obtain 61 target genes of artesunate against bone destruction in RA. The intersected target genes were analyzed by GO/KEGG enrichment. According to the results previously reported, the cytokine-cytokine receptor interaction signaling pathway was selected for experimental verification. Artesunate intervention in the RANKL-induced osteoclast differentiation model showed that artesunate inhibited CC chemokine receptor 3(CCR3), CC chemokine receptor 1(CCR1) and leukemia inhibitory factor(LIF) mRNA expression in osteoclasts in a dose-dependent manner compared with the RANKL-induced group. Meanwhile, the results of immunofluorescence and immunohistochemistry showed that artesunate could dose-dependently reduce the expression of CCR3 in osteoclasts and joint tissues of the CIA rat model in vitro. This study indicated that artesunate regulated the CCR3 in the cytokine-cytokine receptor interaction signaling pathway in the treatment of bone destruction in RA and provided a new target gene for the treatment of bone destruction in RA.
Rats ; Animals ; Arthritis, Experimental/drug therapy* ; Artesunate/therapeutic use* ; Arthritis, Rheumatoid/genetics* ; Transcriptome ; Network Pharmacology ; Osteoclasts ; Receptors, Cytokine/therapeutic use*

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.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*