OBJECTIVE: To evaluate the efficacy and safety of DCAG (decitabine, cytarabine, anthracyclines, and granulocyte colony-stimulating factor) regimen in the treatment of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). METHODS: The clinical data of 64 R/R AML patients received treatment at Chinese PLA General Hospital from January 1st, 2012 to December 31st, 2022 were retrospectively analyzed. Primary endpoints included efficacy measured by overall response rate (ORR) and safety. Secondary endpoints included overall survival (OS), event-free survival (EFS) and duration of response (DOR). The patients were followed from enrollment until death, or the end of last follow-up (June 1st, 2023), whichever occurred first. RESULTS: Sixty-four patients who failed prior therapy were enrolled and completed 1 cycle, and 26 and 5 patients completed 2 and 3 cycles, respectively. Objective response rate was 67.2% ［39: complete remission (CR)/CR with incomplete hematologic recovery (CRi), 4: partial remission (PR)］. With a median follow-up of 62.0 months (1.0-120.9), the median overall survival (OS) was 23.3 and event-free survival was 10.6 months. The median OS was 51.7 months (3.4-100.0) in responders (CR/CRi/PR) while it was 8.4 months (6.1-10.7) in nonresponders ( P <0.001). Grade 3-4 hematologic toxicities were observed in all patients. Four patients died from rapid disease progression within 8 weeks after chemotherapy. CONCLUSION The DCAG regimen represents a feasible and effective treatment for R/R AML.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Cytarabine/administration & dosage* ; Granulocyte Colony-Stimulating Factor/administration & dosage* ; Retrospective Studies ; Male ; Female ; Decitabine ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anthracyclines/administration & dosage* ; Middle Aged ; Adult ; Treatment Outcome ; Aged ; Recurrence

OBJECTIVE: To analyze the efficacy and safety of decitabine-based myeloablative preconditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML). METHODS: The clinical characteristics and efficacy of 115 AML patients who underwent allo-HSCT at the First Medical Center of Chinese PLA General Hospital from August 2018 to August 2022 were retrospectively analyzed, including 37 patients treated with decitabine conditioning regimen (decitabine group) and 78 patients without decitabine conditioning regimen (non-decitabine group). The cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM) and graft versus host disease (GVHD) were analyzed. RESULTS: For the patients in first complete remission (CR1) state before allo-HSCT, the 1-year relapse rates of decitabine group(22 cases) and non-decitabine group(69 cases) were 9.1% and 29.6%, respectively, the difference was statistically significant(P =0.042). The 1-year cumulative incidence of acute graft-versus-host disease (aGVHD) in decitabine group and non-decitabine group was 62.2% and 70.5%, respectively, and the 1-year cumulative incidence of chronic inhibitor-versus-host disease (cGVHD) was 18.9% and 14.1%, respectively, there were no significant differences in the incidence of aGVHD and cGVHD between the two groups (P >0.05). Of the 115 patients, there were no significantly differences in the 1-year CIR(21.7% vs 28.8%, P =0.866), NRM(10.9% vs 3.9%, P =0.203), OS(75.2% vs 83.8%, P =0.131) and LFS(74.6% vs 69.1%, P =0.912) between the decitabine group(37 cases) and the non-decitabine group(78 cases). CONCLUSION Decitabine-based conditioning regimen could reduce the relapse rate of AML CR1 patients with good safety.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation/methods* ; Decitabine/therapeutic use* ; Transplantation Conditioning/methods* ; Retrospective Studies ; Graft vs Host Disease ; Transplantation, Homologous ; Male ; Female ; Adult ; Middle Aged ; Adolescent ; Young Adult

OBJECTIVE: Microcirculatory disturbance is pathologically critical to acute pancreatitis (AP), which can be effectively alleviated by traditional Chinese medicine (TCM) formulas that activate blood flow. However, there has been no evidence-based research to date. Therefore, a well-designed systematic review and meta-analysis is necessary to elucidate the therapeutic transformative benefit of improving microcirculation during AP. This study aims to confirm the therapeutic efficacy of TCM formulas and explore the potential mechanisms underlying their effects on AP treatment. METHODS: Studies from eight databases including Pubmed, Embase, Web of Science, Cochrane Library, CNKI, CBM, Wanfang, and Chinese VIP, were screened for the eligible randomized controlled trials (RCTs). The APACHE II score and effectiveness rate were set as primary outcomes, while mortality rate, complications, total hospital stays, serum amylase recovery time, the time until the disappearance of abdominal pain, microcirculation indicators, and inflammation indicators were chosen as secondary outcomes. A systematic review and meta-analysis were subsequently conducted. Network pharmacology analysis was performed to analyze potential bioactive components with relevant targets of the core herbs included in the TCM formulas for activating blood flow. RESULTS: A total of 51 RCTs (n = 3 721) were included. Compared with conventional western medical treatments alone, TCM groups were associated with lower APACHE II score (SMD =  - 1.36, 95% CI: -2.01 to - 0.71, P = 0.000) and higher effectiveness rate (RR: 1.22, 95% CI: 1.18 to 1.26, P = 0.000). Furthermore, the formulas for activating blood flow demonstrated significant efficacy in improving both microcirculation and inflammation indicators. Additionally, six core Chinese herbal medicines including Rhei Radix et Rhizoma with the highest frequency, Aurantii Fructus Immaturus, Paeoniae Radix Rubra, Bupleuri Radix, Salviae Miltiorrhizae Radix et Rhizoma, and Corydalis Rhizoma were filtered out from the adopted TCM formulas. Finally, 166 shared targets between the six herbs and AP were identified. KEGG analysis indicated that lipid and atherosclerosis pathway is highly related to microcirculation. CONCLUSION TCM formulas for activating blood flow significantly improve microcirculation and alleviate AP. Further high-quality, well-designed RCTs and deep mechanism exploration are required.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

Objective:To observe the inhibitory effect of dobutamine on proliferation of FLT3-ITD mutated acute myeloid leukemia(AML)cells and explore the feasibility of dobutamine as a monotherapy or in combination with quizartinib for the treatment of this type of AML.Methods:FLT3-ITD mutant cell lines MOLM13 and MV4-11 were cultured in vitro and divided into control group,dobutamine treatment group,quizartinib treatment group,and dobutamine combined with quizartinib treatment group.Cell viability,ROS levels,and apoptosis rate were detected by CCK-8,Flow cytometry,respectively,as well as the expression of YAP1 protein by Western blot.Results:Both dobutamine and quizartinib inhibited the proliferation of FLT3-ITD mutant AML cell lines.Compared with the control group,the dobutamine group exhibited a significant increase in ROS levels(P＜0.01),an increase in apoptosis rates(P＜0.05),and a decrease in YAP1 protein expression(P＜0.05).Compared with the dobutamine group,the combination of quizartinib and dobutamine significantly reduced cell viability(P＜0.05),increased ROS levels(P＜0.01),and decreased YAP1 expression(P＜0.05).Conclusion:Dobutamine as a monotherapy can inhibit the proliferation of FLT3-ITD mutated AML cells,inducing apoptosis.Additionally,the combination of quizartinib enhances the targeted inhibitory effect on FLT3-ITD mutated AML.The mechanism may involve the inhibition of YAP1 protein expression in AML cells of this type,leading to an increase in ROS levels and exerting its anti-tumor effects.

Objective To summarize the medication law of TCM in the treatment of chronic bronchitis;To provide reference for clinical medication.Methods Medical records of patients with chronic bronchitis who were hospitalized in the Respiratory Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 1,2016 to December 31,2021 were extracted based on HIS electronic medical record data.After screening,the TCM prescriptions used by patients with chronic bronchitis were input into Excel 2019 to establish a database.Based on the software Lantern 5.0,the latent structure model was learned,hidden variables and explicit variables were obtained,and the model was interpreted.SPSS Modeler 18.0 was used to establish model points with Apriori algorithm for Chinese materia medica with a frequency greater than 6%,to obtain the association rules between drugs,and to analyze the medication law of TCM in treating chronic bronchitis.Results A total of 3 410 cases were included,involving 423 kinds of Chinese materia medica,with a cumulative frequency of 82 766 times.Among them,109 kinds of Chinese materia medica with a frequency of>6 % had a cumulative frequency of 69 845 times.The top five commonly used medicines were Fritillariae Cirrhosae Bulbus,Poria,Atractyodis Macrocephalae Rhizoma,Asteris Radix et Rhizoma,Citri Reticulatae Pericarpium,mainly with medicines of reducing cough and phlegm,antiasthmatic medicine,tonifying deficiency,clearing heat,relieving superficies,promoting blood circulation and removing blood stasis.The medicinal properties were warming,cold and mild,and the main tastes were bitter,sweet and pungent,and the meridians were mainly lung,spleen,liver and stomach meridians.Through analysis of latent structure,49 hidden variables and 149 hidden classes were obtained.Combined with professional knowledge,10 comprehensive clustering models and 21 core formulas were deduced,such as Sangbaipi Decoction,Xuefu Zhuyu Decoction,Xiaoqinglong Decoction,Erchen Decoction,Shashen Maidong Decoction,Liuwei Dihuang Pills,Yinqiao Powder,Zhisou Powder,Yupingfeng Powder,Xuefu Zhuyu Decoction combined with Daotan Decoction,etc.It was concluded that the chronic bronchitis syndrome included phlegm-heat stagnation lung syndrome,qi stagnation blood stasis syndrome,cold fluid attacking lung syndrome,phlegm-dampness accumulation lung syndrome,lung qi and yin deficiency syndrome,kidney yin deficiency syndrome,wind heat attacking lung syndrome,wind cold attacking lung syndrome,lung qi and spleen deficiency syndrome,phlegm stasis interjunction syndrome.A total of 41 strong association rules were screened in the analysis of association rules,including 5 strong association rules for two and 36 strong association rules for three.The high confidence rules were Saposheikovize Radix + Angelicae Sinensis Radix →Atractyodis Macrocephalae Rhizoma,Saposheikovize Radix + Codonopsis Radix → Atractyodis Macrocephalae Rhizoma,Codonopsis Radix + Citri Reticulatae Pericarpium → Atractyodis Macrocephalae Rhizoma;the higher degree of improvement were Bupleuri Radix + Mori Cortex → Scutellariae Radix,Perillae Fructus + Belamcandae Rhizoma → Fritillariae Cirrhosae Bulbus,Armeniacae Semen Amarum + Pinelliae Rhizoma → Citri Reticulatae Pericarpium,etc.Conclusion In the treatment of chronic bronchitis,TCM is mainly used to reduce phlegm,relieve cough and asthma,and the method of promoting blood circulation and removing blood stasis is commonly used to help eliminate phlegm.In addition,TCM pays attention to the application of methods such as tonifying lung and securing the exterior,invigorating spleen and benefiting qi.

Objective:To analyze the clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infections in children, and to provide reference basis for the SARS-CoV-2 vaccination in children.Methods:A total of 97 children aged 3 to 14 years and diagnosed with coronavirus disease 2019 (COVID-19) admitted to Xi′an People′s Hospital (Xi′an Fourth Hospital) from December 27, 2021 to February 7, 2022 were included. According to the COVID-19 vaccination status, the enrolled children were divided into unvaccinated group, partially vaccinated group and fully vaccinated group, and the clinical data of the children in the three groups were collected and compared. Chi-square test, two independent sample t-test and Kruskal-Wallis H test were used for statistical analysis. Results:Totally 97 children including 49 males and 48 females were enrolled, with 87(89.7%) children of mild type, 10(10.3%) children of common type, and no severe or critical case. The proportions of unvaccinated, partially vaccinated and fully vaccinated preschool-aged children (3 to 6 years old) were 56.5%(13/23), 30.8%(12/39) and 17.1%(6/35), respectively, while those of school-aged children (7 to 14 years old) were 43.5%(10/23), 69.2%(27/39) and 82.9%(29/35), respectively. The vaccination proportion in preschool-aged children was significantly lower than that in school-age children ( χ2=9.94, P=0.007). The proportion of the children with fever in fully vaccinated group was 17.1%(6/35), which was lower than that in unvaccinated group (43.5%, 10/23), and the difference was statistically significant ( χ2=4.82, P=0.028). The cycle threshold (Ct) values of the open reading frame ( ORF)1 ab gene in the unvaccinated, partially vaccinated and fully vaccinated groups were 33.77(26.87, 36.58), 35.23 (33.45, 38.57) and 37.12 (34.91, 39.39), respectively, and there was a statistically significant difference among the groups ( H=7.76, P=0.021). The Ct values of the nucleocapsid protein ( N) gene in the three groups were 32.26(25.85, 36.18), 35.12(33.18, 37.96) and 37.26(34.27, 39.24), respectively, and the difference among the groups was statistically significant ( H=7.84, P=0.020). The Ct values of ORF1 ab gene and N gene in fully vaccinated group were higher than those in unvaccinated group, and the differences were statistically significant ( Z=-2.69, P=0.007 and Z=-2.39, P=0.017, respectively). The duration of viral shedding in fully vaccinated children was (9.9±4.1) d, which was shorter than that in unvaccinated children ((12.8±3.7) d), and the difference was statistically significant ( t=2.72, P=0.009). Conclusions:The majority of children with breakthrough infections with SARS-CoV-2 are mild. Vaccination may effectively shorten the duration of viral shedding. And fully vaccination is associated with mild clinical symptoms and lower serum viral load compared to unvaccinated children.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Objective:To explore KRAS, NRAS, BRAF gene mutations and microsatellite instability(MSI) in colorectal cancer tissues as well as their correlation with the clinicopathological characteristics of patients.Methods:The clinicopathological data of 473 colorectal cancer patients in Shanxi Province Cancer Hospital from October 2020 to May 2021 were retrospectively analyzed. The mutation status of KRAS, NRAS and BRAF gene in the paraffin tissues were detected by using amplification refractory mutation system (ARMS) method. Polymerase chain reaction (PCR)-capillary electrophoresis was used to analyze MSI status, and the correlation of the clinicopathological characteristics of patients with gene mutations and MSI status was analyzed.Results:The mutation rates of KRAS, NRAS and BRAF were 45.03% (213/473), 2.96% (14/473) and 5.50% (26/473), respectively in 473 patients with colorectal cancer. No case harbored both 2 gene mutations was detected. The mutation rate of KRAS gene in well differentiated adenocarcinoma was higher than that in poorly differentiated adenocarcinoma [47.4% (175/369) vs. 36.5% (38/104), χ2 = 3.89, P = 0.049]. NRAS mutation rate in female was higher than that in male [5.0% (10/202) vs. 1.5% (4/271), χ2 = 4.86, P = 0.027], and the NRAS mutation rate in patients with tumor diameter ≤ 3 cm was higher than that in those with tumor diameter >3 cm [7.1% (7/98) vs. 1.9% (7/375), P = 0.013]. BRAF mutation rate of tumors located in colon was higher than that in rectum [11.7% (20/171) vs.2.0% (6/302), χ2 = 19.81, P < 0.001]; BRAF mutation rate in poorly differentiated tumor was higher than that in well differentiated tumor [10.6% (11/104) vs. 4.1% (15/369), χ2 = 6.62, P = 0.010]; BRAF mutation rate in patients with mucus was higher than that in those without mucus [10.9% (11/101) vs. 4.0% (15/372), χ2 = 7.19, P = 0.007]; BRAF mutation rate in patients with lymphatic metastasis was higher than that in patients without lymphatic metastasis [8.2% (15/182) vs.3.8% (11/291), χ2 = 4.29, P = 0.038]. The incidence of high frequency MSI (MSI-H) in 473 colorectal cancer tissues was 7.19% (34/473). The incidence of MSI-H in colon was higher than that in rectum [14.0% (24/171) vs. 3.3% (10/302), χ2 = 18.82, P < 0.001]; the incidence of MSI-H in patient with poor differentiated tumor was higher than that in those with well differentiated tumor [17.3% (18/104) vs. 4.3% (16/369), χ2 = 20.46, P < 0.001]; the incidence of MSI-H in patients with mucus was higher than that in those without mucus [11.9% (12/101) vs. 5.9% (22/372), χ2 = 4.24, P = 0.039]; and the incidence of MSI-H in patients without lymphatic metastasis was higher than that in patients with lymphatic metastasis [10.0% (29/291) vs. 2.7% (5/182), χ2 = 8.75, P = 0.003]. In addition, the incidence of MSI-H was on the rise in patients with BRAF mutation ( P < 0.001). Conclusions:KRAS, NRAS, BRAF gene mutations and MSI status are correlated with the clinicopathological characteristics of patients with colorectal cancer; there is a close relationship between MSI-H and BRAF mutation.

Objective:To systematically evaluate the efficacy of different kinds of smoking cessation drugs by network Meta-analysis.Methods:Literature was retrieved from PubMed, Web of Science, Embase, Cochrane Library, CBM, CNKI, VIP, Wan fang database, from the establishment of the database to November 2022, and randomized controlled trials (RCT) about bupropion, varenicline, nicotine replacement therapy (NRT) versus placebo in the treatment of smoking patients were collected. After data extraction from included literature which met inclusion criteria, and quality evaluation with Cochrane 5.1 risk bias evaluation tool, network Meta-analysis was performed by Stata15.1 software.Results:A total of 19 RCTs, involving 6106 patients and three interventions measures (bupropion, varenicline, NRT) and one control measure (placebo) were included. The results of network Meta-analysis showed that in terms of short-term abstinence rate, varenicline [ OR=4.21, 95% CI (2.32, 7.63)], bupropion [ OR=2.81, 95% CI(1.05, 7.54)] were better than placebo ( P<0.05). The surface under the cumulative ranking area (SUCRA): varenicline (90.2%)>bupropion (64.8%)>NRT (41.7%)>placebo (3.2%). In terms of the long-term abstinence rate, varenicline [ OR=3.06, 95% CI (1.59, 5.90)], NRT [ OR=3.39, 95% CI (2.20, 5.21)] were better than placebo ( P<0.05). SUCRA: varenicline (83.8%)>NRT (73.9%)>bupropion (37.2%)>placebo (5.2%). Conclusion:The existing evidence shows that compared with bupropion, NRT, varenicline has the best effect on quitting smoking, but more high-quality randomized trial evidence is needed for verification.