Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To study the mechanism of icariin inhibiting the proliferation of human PCa PC-3 cells based on cell metabolomics technology.Methods:We determined the proliferation activity of human PC-3 cells by methyl thiazolyl tetrazolium(MTT)assay,and compared the proliferation of the PC-3 cells among the control,5-fluorouracil and icariin intervention groups.Using the Bligh Dyer method,we extracted endogenous metabolites from the cells,analyzed the metabolic profile by ultra-high pressure liquid chromatography tandem quadrupole time-of-flight mass spectrometry,identified the differential metabolites by principal component anal-ysis and orthogonal partial least-squares discrimination analysis,and enriched the metabolic pathways based on the MetaboAnalyst data-base.Results:Icariin significantly inhibited the proliferation of human PCa PC-3 cells.A total of 89 differential metabolites were i-dentified,mainly including amino acids,phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine,and lysophosphati-dylethanolamine,all with the tendency to return to the normal level after icariin intervention.Icariin significantly downregulated the metabolic levels of the glycerophospholipid metabolites phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine and ly-sophosphatidylethanolamine,and upregulated those of amino acid metabolites tryptophan,leucine,and proline in the PC-3 cells.Conclusion:Icariin inhibits the proliferation of human PCa PC-3 cells,which may be closely related to its regulatory effect on lipid metabolism(glycerophospholipid metabolism)and amino acid metabolism.

Objective: To examine the clinical effect of auxiliary liver transplantation with ultra-small volume graft in the treatment of portal hypertension. Methods: Twelve cases of portal hypertension treated by auxiliary liver transplantation with small volume graft at Liver Transplantation Center,Beijing Friendship Hospital, Capital Medical University between December 2014 and March 2022 were studied retrospectively. There were 8 males and 4 females,aged 14 to 66 years. Model for end-stage liver disease scores were 1 to 15 points and Child scores were 6 to 11 points. The grafts was derived from living donors in 9 cases,from split cadaveric donors in 2 cases,from whole cadaveric liver of child in 1 case. The graft recipient body weight ratios of 3 cadaveric donor livers were 0.79% to 0.90%, and of 9 living donor livers were 0.31% to 0.55%.In these cases, ultra-small volume grafts were implanted. The survivals of patient and graft, complications, portal vein blood flow of residual liver and graft, abdominal drainage and biochemical indexes of liver function were observed. Results: All the grafts and patients survived. Complications included outflow tract torsion in 2 cases, acute rejection in 1 case, bile leakage in 1 case, and thyroid cancer at the later stage of follow-up in 1 case, all of which were cured. The torsion of outflow tract was attributed to the change of anastomotic angle after the growth of donor liver. After the improvement of anastomotic method, the complication did not recur in the later stage. There was no complication of portal hypertension. The measurement of ultrasonic portal vein blood flow velocity showed that the blood flow of residual liver decreased significantly in the early stage after operation, and maintained a very low blood flow velocity or occlusion in the long term after operation, and the blood flow of transplanted liver was stable. Conclusions: Auxiliary liver transplantation can implant ultra-small donor liver through compensation of residual liver. This method may promote the development of living donor left lobe donation and split liver transplantation. However, the auxiliary liver transplantation is complex, and it is difficult to control the complications. Therefore, this method is currently limited to centers that are skilled in living related liver transplantation and that have complete ability to monitor and deal with complications.
Male ; Child ; Female ; Humans ; Liver Transplantation/methods* ; End Stage Liver Disease/surgery* ; Retrospective Studies ; Living Donors ; Severity of Illness Index ; Neoplasm Recurrence, Local ; Liver/blood supply* ; Hypertension, Portal/surgery* ; Portal Vein ; Cadaver

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

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*

The plateau environment is characterized by low oxygen, low air pressure, low temperature, and strong ultraviolet rays, etc. Chronic obstructive pulmonary disease (COPD) is a preventable and treatable chronic lung disease. High altitude environment increases COPD prevalence, clinical manifestation and mortality. The therapeutic window of theophylline drugs for COPD is narrow, and the high altitude environment has an influence on the pharmacokinetics of the drugs. This review summarizes the differences in the prevalence, mortality, clinical manifestation and clinical symptoms of COPD in the plateau and plain, providing a basis for identifying the risk factors of COPD in the plateau areas. The effects of plateau hypoxic environment on the pharmacokinetics of COPD drugs were also discussed. It can provide a rationale for more effective prevention and treatment of COPD at high altitude.
Humans ; Altitude ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Oxygen ; Hypoxia

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

OBJECTIVE: To analyze the causes of vertebral fracture during oblique lateral interbody fusion in the treatment of lumbar spondylopathy, summarize the clinical results, and propose preventive measures. METHODS: Retrospective analysis was made on the data of 8 cases of lumbar spondylopathy and vertebral fracture treated by oblique lateral interbody fusion in three medical centers from October 2014 to December 2018. All were female, aged from 50 to 81 years with an average of 66.4 years. Disease types included 1 case of lumbar degenerative disease, 3 cases of lumbar spinal stenosis, 2 cases of lumbar degenerative spondylolisthesis and 2 cases of lumbar degenerative scoliosis. Preoperative dual energy X-ray bone mineral density test showed that 2 cases had T-value >-1 SD, 2 cases had T-value -1 to -2.5 SD, and 4 cases had T-value <-2.5 SD. Single segment fusion was in 5 cases, two segment fusion in 1 case and three segment fusion in 2 cases. Four cases were treated with OLIF Stand-alone and 4 cases were treated with OLIF combined with posterior pedicle screw fixation. Postoperative imaging examination showed vertebral fracture, and all of them were single vertebral fracture. There were 2 cases of right lower edge fracture of upper vertebral body at fusion segment, 6 cases of lower vertebral body fracture at fusion segment, and 6 cases with endplate injury and fusion cage partially embedded in vertebral body. Three cases of OLIF Stand-alone were treated with pedicle screw fixation via posterior intermuscular approach, while one case of OLIF Stand-alone and four cases of OLIF combined with posterior pedicle screw fixation were not treated specially. RESULTS: The 5 cases of initial operation and 3 cases of reoperation did not show wound skin necrosis or wound infection. The follow-up time was from 12 to 48 months with an average of 22.8 months. Visual analogue scale (VAS) of low back pain was preoperative decreased from 4 to 8 points (averagely 6.3 points) and postoperative 1 to 3 points (averagely 1.7 points) at the final follow-up. Oswestry disability index (ODI) was preoperative 39.7% to 52.4% (averagely 40.2%), and postoperative 7.9% to 11.2% (averagely 9.5%) at the final follow-up. During the follow-up, there was no loosening or fracture of the pedicle screw system, and no lateral displacement of the fusion cage;however, the fusion cage at the vertebral fracture segment had obvious subsidence. The intervertebral space height of vertebral fracture segment was preoperaive 6.7 to 9.2 mm (averagely 8.1 mm), and postoperative 10.5 to 12.8 mm (averagely 11.2 mm). The improvement rate after operation was 37.98% compared to preoperative. The intervertebral space height at final follow-up was 8.4 to 10.9 mm (averagely 9.3 mm), and the loss rate was 16.71% compared with that after operation. At the final follow-up, interbody fusion was achieved in all cases except for one that could not be identified. CONCLUSION The incidence of vertebral fracture during oblique lateral interbody fusion in the treatment of lumbar spondylopathy is lower, and there are many reasons for fracture, including preoperative bone loss or osteoporosis, endplate injury, irregular shape of endplate, excessive selection of fusion cage, and osteophyte hyperplasia at the affected segment. As long as vertebral fracture is found in time and handled properly, the prognosis is well. However, it still needs to strengthen prevention.
Humans ; Female ; Male ; Spinal Fractures/surgery* ; Retrospective Studies ; Treatment Outcome ; Lumbar Vertebrae/surgery* ; Spondylolisthesis/surgery* ; Scoliosis ; Spinal Fusion/methods*

Objective:To investigate the risk of stroke in elderly hypertensive(HTN)patients with varying baseline triglyceride glucose(TYG)index, and to identify the risk factors associated with stroke in this population.Methods:This study was a prospective cohort study that included 459 elderly patients with hypertension who were admitted to Beijing Anzhen Hospital from January 2018 to January 2020.The patients were divided into four groups based on their quartile of TYG index: Q1 group(TYG index≤8.02, 114 cases), Q2 group(8.028.85, 115 cases). The study compared the baseline clinical data and incidence of stroke(hemorrhagic or ischemic stroke)after two years of follow-up among the four groups, and analyzed the risk factors of stroke using Cox regression analyses.Results:This study examined 459 elderly patients with hypertension, of which 251(54.7%)were male and 208(45.3%)were female, with an average age of(71.7 ± 6.2)years(65-79 years). The study found significant differences among the four groups in various factors( P<0.05 for all). The study followed up with patients for a median of 33 months, 55 cases were lost to follow-up.Out of the remaining patients, 10.9% experienced stroke, with 3.7% being hemorrhagic stroke and 7.2% being ischemic stroke.The occurrence of stroke was observed in 5.3%, 8.7%, 13.0%, and 16.2% of patients in the Q1, Q2, Q3, and Q4 groups, respectively.The results of Kaplan-Meier survival analysis demonstrated that the risk of stroke increased gradually as the quartile increased.Specifically, compared to the Q1 group, the risk of stroke increased by 1.016 times(95% CI: 0.933-1.106, P=0.715), 1.264 times(95% CI: 1.067-1.497, P=0.007), and 1.472 times(95% CI: 1.119-1.936, P=0.006)in the Q2, Q3, and Q4 groups, respectively.Notably, both Q3 and Q4 groups showed a significant increase in the risk of ischemic stroke( HR=1.313, 95% CI: 1.016-1.697, P=0.037; HR=1.509, 95% CI: 1.113-2.046, P=0.008), while the Q4 group showed a significant increase in the risk of hemorrhagic stroke( HR=1.132, 95% CI: 1.021-1.255, P=0.019). Multivariate Cox regression analysis showed that male( HR=1.336), smoking history( HR=1.485), hyperlipidemia( HR=1.216), previous stroke( HR=1.547), sleep apnea( HR=1.484), diastolic blood pressure( HR=1.114), hemoglobin( HR=0.962), albumin/creatinine ratio( HR=1.318), low-density lipoprotein cholesterol( HR=1.125), TYG index( HR=1.293), left ventricular mass index( HR=1.103), and anti-platelet therapy( HR=0.874)were all found to be independent risk factors for stroke. Conclusions:In elderly patients with hypertension, there is a significant positive correlation between TYG index and stroke risk, particularly ischemic stroke.This suggests that TYG index could be clinically valuable in improving cerebrovascular risk stratification.

Objective:To evaluate the effect of Empagliflozin on the incidence of major adverse cardiovascular events(MACE)in elderly patients with heart failure and reduced ejection fraction(HFrEF)over a period of 1 year.Additionally, the study will analyze the influence of frailty on MACE.Methods:This study is a retrospective analysis of 577 elderly patients with type 2 diabetes and heart failure with reduced ejection fraction(HFrEF)who were consecutively admitted to Beijing Anzhen Hospital from January 2018 to December 2020.The patients were divided into three groups according to frailty index(FI): non-frailty(FI ≤ 0.210, 301 cases), moderate frailty(FI 0.211-0.310, 184 cases), and severe frailty(FI>0.311, 92 cases).Additionally, a control group of 300 elderly HFrEF patients with T2DM who did not receive Sodium glucose co-transporter type 2(SGLT-2)inhibitors was included.The MACE outcomes of different patient groups who were followed up for a year after discharge were compared.The composite outcomes of cardiac death, worsening heart failure readmission, non-fatal myocardial infarction, and non-fatal stroke were recorded and analyzed.The study also includes Cox regression analysis of relevant factors that may affect MACE outcomes.Results:A total of 877 patients were monitored for a period of 7-14 months, with a median follow-up duration of(11.4±2.3)months.Out of these patients, 47(5.4%)were lost to follow-up.During the follow-up period, 108 patients(18.7%)in the Empagliflozin group experienced major adverse cardiovascular events(MACE), which included 43 patients(7.5%)with heart failure readmission, 29 patients(5.0%)with non-fatal myocardial infarction, 23 patients(4.0%)with non-fatal stroke, and 13 patients(2.3%)with cardiovascular death.The control group had 73 cases of major adverse cardiac events(MACE), which included 33 cases(11.0%)of readmission due to heart failure, 18 cases(6.0%)of non-fatal myocardial infarction, 14 cases(4.7%)of non-fatal stroke, and 8 cases(2.7%)of cardiovascular death.The Kaplan-Meier survival analysis revealed significant differences in the risk of readmission for heart failure exacerbation and MACE among the groups.The study found that the Empagliflozin group had a significantly lower risk of MACE(18.7% vs.24.3%, HR=0.792, 95% CI: 0.639-0.982, P=0.033)compared to the control group.Additionally, as frailty level increased, the risk of MACE in each empagliflozin subgroup also increased significantly(14.6% vs.19.6% vs.30.4%, P<0.001).The moderate and severe frailty groups had a 1.342 times( HR=1.342, 95% CI: 1.116-1.768, P=0.022)and 1.933 times( HR=1.933, 95% CI: 1.207-3.854, P=0.019)higher risk of MACE compared to the non-frailty group.The study conducted a multivariate Cox regression analysis and found that several factors were independently associated with the risk of MACE, including age( HR=1.164), duration of heart failure( HR=1.225), B-type natriuretic peptide level( HR=1.221), albumin/creatinine ratio( HR=1.158), renin-angiotensin-aldosterone system blocker( HR=0.891), frailty index( HR=1.764), and empagliflozin( HR=0.792)( P<0.05 for all). Conclusions:Empagliflozin has been shown to reduce the risk of major adverse cardiovascular events(MACE)in patients with heart failure with reduced ejection fraction(HFrEF).However, it is important to note that the cardiovascular benefits of SGLT-2 inhibitors may be affected by frailty in elderly patients with heart failure.As frailty worsens, the risk of readmission and MACE may increase significantly.