1.Causal association between six metabolites and atopic dermatitis:a bidirectional two-sample Mendelian randomization study
Yan WEI ; Yan SUN ; Lijuan WANG ; Shuai SHAO ; Yan ZHENG
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):801-808
Objective We made a bidirectional two-sample Mendelian randomization(MR)analysis to investigate the causal connection between metabolites and atopic dermatitis(AD).Methods Single nucleotide polymorphic(SNP)sites associated with metabolites were extracted from the aggregated data of a genome-wide association study(GWAS)as instrumental variables.Causal association between six metabolites and AD was analyzed using the TwoSampleMR package in R software.The primary methods employed included inverse variance weighted(IVW),MR Egger,and weighted median.Heterogeneity testing was conducted using Cochran's Q statistics.MR Egger intercept was employed to test for level pleiotropy.Additionally,sensitivity analysis was carried out using the"leave-one-out"approach.Results The IVW analysis results indicated that ascorbic acid(OR=0.861,95%CI:0.751-0.987),arachidonic acid(OR=0.363,95%CI:0.193-0.683),and cortisone(OR=0.447,95%CI:0.221-0.906)were negatively correlated with the occurrence of AD,while uridine(OR=3.473,95%CI:1.043-11.562),serotonin(OR=1.896,95%CI:1.007-3.571),and 2-hydroxyglutaric acid(OR=2.158,95%CI:1.186-3.924)were positively correlated with the occurrence of AD,and the differences were statistically significant.Conclusion There is no significant evidence supporting a causal association between AD and metabolic disorder,but this study identified potential evidence for a causal effect of six metabolic factors on an increased risk of AD.
2.Pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy in the treatment of chronic pancreatitis: initial experience in 11 cases
Shuai WU ; Wanxing DUAN ; Xue YANG ; Wanzhen WEI ; Qingyong MA ; Zheng WANG ; Zheng WU
Chinese Journal of Surgery 2024;62(5):412-418
Objective:To investigate the surgical strategy for chronic pancreatitis complicated with suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas.Methods:This is a retrospective cohort study. Clinical data from 11 patients with chronic pancreatitis who underwent pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy(PD-L) were retrospectively collected(PD-L group) from the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi′an Jiaotong University between December 2021 and September 2023. All patients were male with an age of (49.0±11.2) years(range:32 to 70 years). Their primary preoperative diagnoses included pancreatic lesions, chronic pancreatitis, pancreatolithiasis, and dilatation of the pancreatic duct. Data from 248 patients who underwent pancreaticoduodenectomy(PD) during the same period were retrospectively collected(PD group). There were 157 males and 91 females in the PD group, with an age of (61.5±10.8) years(range:27 to 82 years). Among them, 87 cases were diagnosed as pancreatic cancer or chronic pancreatitis. The propensity score matching method was used to reduce confounding bias between the two groups. The caliper value of 0.1 was used and the 1∶4 nearest neighbor matching method was used for the matching. Comparisons between the two groups were made using the independent sample t test, Mann-Whitney U test or χ2 test,respectively. Results:After complete excision of the specimen during pancreaticoduodenectomy, the key surgical step of PD-L was longitudinal pancreaticojejunostomy in the remaining pancreas. Intraoperative blood loss in the PD-L group was lower than that in the PD group [ M(IQR)](300(200)ml vs. 500(500)ml, respectively; P<0.05). Similarly, hospitalization days(21.0(7.0)days vs. 25.0(8.5)days) and postoperative hospitalization days(13.0(8.0)days vs. 17.0(5.0) days) were also lower in the PD-L group compared to the PD group ( P<0.05). There were no significant differences in the operation time and postoperative complication rate between the two groups( P>0.05). In the PD-L group, the postoperative follow-up time was 5(5)months(range: 3 to 21 months). One case was lost for follow-up. Abdominal pain was relieved in 10 patients. Additionally, abdominal distension and steatosis were alleviated in 8 cases. Furthermore, 5 cases of diabetes mellitus showed improved control of HbA1c and fasting blood glucose levels after surgery. Conclusions:PD-L treatment can be used to treat chronic pancreatitis complicated by suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas. PD-L also has advantages in removing stones from the pancreatic duct and evaporation of pancreatic fluid. However, due to the single-center design and the small sample size of this study, further practice and long-term follow-up are still necessary.
3.Structure-activity Omics of Anti-inflammatory and Analgesic Effect of Corydalis Rhizoma in Qizhi Weitong Granules
Xinpeng QIN ; Ying MENG ; Sicong LIU ; Ying ZHENG ; Yongrui BAO ; Shuai WANG ; Tianjiao LI ; Ling HAN ; Wei ZOU ; Xiansheng MENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):136-145
ObjectiveTo explain the anti-inflammatory and analgesic effects of Corydalis Rhizoma by the means of structure-activity omics. MethodOn the basis of the previous in vitro screening study, we studied the in vivo efficacy of the alkaloids in Corydalis Rhizoma. With the targets as a bridge, the structures of chemical components in Corydalis Rhizoma were connected with the efficacy. The molecular docking of the alkaloids in Corydalis Rhizoma with the targets of inflammation and pain was carried out. According to the docking scores and the differences in the structural nucleus of Corydalis Rhizoma alkaloids, a study of structure-activity omics was carried out to summarize the rules of their connection. ResultThe alkaloids in Corydalis Rhizoma had good anti-inflammatory and analgesic effects in vivo, involving 53 chemical components and 73 targets. There were 3 074 targets associated with inflammation and pain, and 42 targets of direct action were shared by the chemical components and the disease. The protein-protein interaction (PPI) and molecular docking analysis predicted that the main active components of Corydalis Rhizoma were tetrahydropalmatine and palmatine, and the core targets were prostaglandin endoperoxide synthase 2 (PTGS2), glutamate receptor metabotropic 5 (GRM5), estrogen receptor 1 (ESR1), solute carrier family 6 member 4 (SLC6A4), and fusion oncoproteins (FOS). According to the differences of mother nucleus, the 53 alkaloid components of Corydalis Rhizoma were classified into 8 categories, including protoberberine, berberine, and aporphine, which had high binding affinities with PTGS2, GRM5 and other targets. The relationship between the structures of Corydalis Rhizoma alkaloids and docking scores in each group showed the same law. In protoberberine, appropriate substituents with hydroxyl, alkoxy or methyl groups on the A and D rings of the parent ring were conducive to enhancing the binding activities with the two targets. In berberine, the structure containing a methyl group on position 13 had strong binding affinities with the two targets. It is hypothesized that the methyl fragment changes the binding mode between the component structure and amino acid residues, which greatly improves the binding affinity. ConclusionThis study employs the method of structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of alkaloids in Corydalis Rhizoma, and the structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.
4.Clinical characteristics and treatment mode changes of chronic pancreatitis: a 10-year single center study
Wanzhen WEI ; Wanxing DUAN ; Jinpeng ZHAO ; Shuai WU ; Weikun QIAN ; Zheng WU ; Xue YANG ; Zheng WANG
Chinese Journal of Digestive Surgery 2024;23(5):726-732
Objective:To investigate the clinical characteristics and treatment mode changes of chronic pancreatitis (CP).Methods:The retrospective and descriptive study was conducted. The clinical data of 805 patients with CP who were admitted to the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to December 2022 were collected. There were 575 males and 230 females, aged 52(range, 10-87)years. Observation indicators: (1)demographic characteristics; (2)distribution of admission departments, hospitalization and treatment status. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distri-bution were represented as M(range). Count data were expressed as absolute numbers and percentages. The chi-square goodness-of-fit test was used for consistent between expected frequency and empirical distribution. Results:(1)Demographic characteristics. Of the 805 patients, there were 435 cases and 370 cases diagnosed as CP according to the primary and secondary diagnostic criteria, respec-tively, and the age of initial presentation of 805 patients was 52(range, 10-87)years. Among male and female patients, there was 1 and 0 case in the age group of 0-10 years, there were 16 and 14 cases in 11-20 years, 45 and 26 cases in 21-30 years, 82 and 30 cases in 31-40 years, 122 and 39 cases in 41-50 years, 157 and 51 cases in 51-60 years, 119 and 46 cases in 61-70 years, 31 and 21 cases in 71-80 years, 2 and 3 cases in 81-90 years, respectively. Patients aged 0-14, 15-34, 35-64, and ≥65 years were 0, 6, 28, and 9 for 2013, 1, 21, 34, and 10 for 2014, 1, 8, 38, and 7 for 2015, 0, 7, 52, and 10 for 2016, 0, 11, 35 and 9 for 2017, 1, 15, 72 and 23 for 2018, 0, 9, 55 and 11 for 2019, 2, 19, 58 and 16 for 2020, 0,20, 79 and 18 for 2021, 0, 25, 73 and 22 for 2022, respectively. Of the 805 patients, cases from Shaanxi Province, Gansu Province and other regions were 702, 48 and 55, respectively. There are 802 Han and 3 Hui patients, respectively, and the married, unmarried, divorced, and widowed patients were 732, 64, 7, and 2, respectively. Cases with blood type information was 682, with the distribution of blood types as 26.10%(178/682) of type A, 34.46%(235/682)of type B, 9.97%(68/682) of type AB, 29.47%(201/682)of type O, showing no significant difference compared to the distribu-tion of blood types in population of Shaanxi Province in 2022 (28.43% of type A, 30.50% of type B, 9.83% of type AB, and 30.50% of type O) ( χ2=0.50, P>0.05). (2)Distribution of departments, hospita-lization, and treatment. Of the 805 patients, cases admitted to the Department of Hepatobiliary Surgery, Department of Gastroenterology and other departments (Department of Geriatric Surgery, Infectious Diseases and General Surgery) were 594, 121 and 90, respectively. Cases of the number of hospitalizations in the Department of Hepatobiliary Surgery, Department of Gastroenterology and other departments were 771, 121 and 94, respectively. One patient might have been admitted for multiple times. The duration of hospital of stay of 805 patients was 11(rang, 1-67)days. The duration of hospital stay of patients admitted to the Department of Hepatobiliary Surgery, Department of Gastroenterology and other departments were 16(range, 2-48)days, 11(range, 5-19)days and 24(range, 12-35)days for 2013, 18(range, 2-63)days, 10(range, 3-29)days and 14(range, 7-30)days for 2014, 9(range, 1-35)days, 11(range, 2-16)days and 10(range, 5-33)days for 2015, 10(range, 1-55)days, 9(range, 4-16)days and 16(range, 4-27)days for 2016, 9(range, 2-38)days, 10(range, 4-20)days and 11(range, 5-27)days for 2017, 12(range, 3-46)days, 11(range, 2-26)days and 13(range, 7-27)days for 2018, 11(range, 1-33)days, 9(range, 3-23)days and 14(range, 4-17)days for 2019, 11(range, 1-67)days, 7(range, 1-23)days, and 16(range, 4-27)days for 2020, 10(range, 1-35)days, 8(range, 1-32)days and 14(range, 1-29)days for 2021, 9(range, 1-42)days, 12(range, 3-17)days and 11(range, 1-22)days for 2022. Of the 805 patients, cases receiving treatment as surgical treatment, pancreas extracorporeal shock wave lithotripsy (P-ESWL), endoscopic treatment and other treatments were 258, 117, 194 and 236, respectively. A total of 260 surgeries were performed on 258 patients receiving surgical treatment, and there were 236 cases receiving surgical treatment as the first choice, and 22 cases undergoing surgery after failed of other treatments. The surgical procedures included pancreaticoduodenectomy in 79 cases, distal pancreatectomy (with or without splenectomy, Peustow procedure) in 35 cases, partial pancreatectomy with pancreatic duct incision and stone removal and pancreaticojejunostomy in 77 cases, simple pancreatic duct incision and pancreaticojejunostomy in 58 cases, internal drainage for pancreatic pseudocysts in 4 cases, and drainage for removal of pancreatic necrotic tissue in 7 cases. There were 58 patients with post-operative complications, including 9 cases of bleeding, 19 cases of infection, 2 cases of gastric paresis, 21 cases pancreatic fistula, and 7 cases of intestinal leakage. Cases with postoperative complications were recovered and discharged after symptomatic treatment. Of the 117 patients receiving P-ESWL, the times of treatment per patient was 1.3±0.7, and a total of 154 times of P-ESWL were performed. There were 89 patients receiving one time of P-ESWL, and 28 patients receiving ≥2 times of P-ESWL. Of the 194 patients receiving endoscopic treatment, the times of treatment per patient was 1.2±0.6, and a total of 238 times of endoscopic treatment were performed. There were 103 cases receiving stent placement, 43 cases receiving nasopancreatic/nasobiliary drainage, 7 cases receiving pancreatic duct balloon dilation, 71 cases receiving pancreatic stone removal, and 58 cases receiving duodenal papilla sphincterotomy. There were 168 patients receiving one time of endoscopic treatment, and 26 patients receiving ≥2 times of endoscopic treatment.There was no postoperative complica-tions reported. Conclusions:The proportion of males in CP patients is relatively high, and the proportion gradually increases with age of 51-60 years. There is no significant difference in the distribution of blood types among CP patients and the population of Shaanxi Province. The proportion of minimally invasive treatment (extracorporeal shock wave lithotripsy and endoscopic therapy) in CP treatment is on the rise, and the duration of hospital stay for patients is on the decline.
5.The progress and implications of interatrial shunt
San-Shuai CHANG ; Xin-Min LIU ; Zheng-Ming JIANG ; Wei MA ; Jian-Zeng DONG ; Guang-Yuan SONG
Chinese Journal of Interventional Cardiology 2024;32(8):463-467
Despite significant advancements in treatments for heart failure,the overall prognosis for patients remains poor.Hemodynamic abnormalities in heart failure manifest as elevated left atrial pressure and pulmonary congestion.Previous studies have shown that reducing left atrial pressure can improve symptoms and prognosis for heart failure patients,suggesting that left-sided heart overload may be a potential target for heart failure treatment.Atrial shunting procedures aim to create a stable and controlled left-to-right intracardiac shunt,restoring the decompensated left heart volume and pressure load in heart failure patients to a compensatory state,thereby improving heart failure symptoms and prognosis.Currently,this treatment is still in the clinical research stage globally.Existing data indicate that atrial shunting procedures can lower left atrial pressure at rest or during exercise in heart failure patients,improve pulmonary congestion,enhance patients'exercise tolerance,and clinical cardiac function.However,no studies have yet confirmed that it can improve clinical endpoints such as rehospitalization and mortality due to heart failure.Future research will focus on identifying heart failure patients who may benefit from atrial shunting,with assessments of heart failure etiology,right heart function,and reversibility of pulmonary vascular resistance,as well as heart failure classification based on ejection fraction,serving as potential key factors for patient selection.
6.Pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy in the treatment of chronic pancreatitis: initial experience in 11 cases
Shuai WU ; Wanxing DUAN ; Xue YANG ; Wanzhen WEI ; Qingyong MA ; Zheng WANG ; Zheng WU
Chinese Journal of Surgery 2024;62(5):412-418
Objective:To investigate the surgical strategy for chronic pancreatitis complicated with suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas.Methods:This is a retrospective cohort study. Clinical data from 11 patients with chronic pancreatitis who underwent pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy(PD-L) were retrospectively collected(PD-L group) from the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi′an Jiaotong University between December 2021 and September 2023. All patients were male with an age of (49.0±11.2) years(range:32 to 70 years). Their primary preoperative diagnoses included pancreatic lesions, chronic pancreatitis, pancreatolithiasis, and dilatation of the pancreatic duct. Data from 248 patients who underwent pancreaticoduodenectomy(PD) during the same period were retrospectively collected(PD group). There were 157 males and 91 females in the PD group, with an age of (61.5±10.8) years(range:27 to 82 years). Among them, 87 cases were diagnosed as pancreatic cancer or chronic pancreatitis. The propensity score matching method was used to reduce confounding bias between the two groups. The caliper value of 0.1 was used and the 1∶4 nearest neighbor matching method was used for the matching. Comparisons between the two groups were made using the independent sample t test, Mann-Whitney U test or χ2 test,respectively. Results:After complete excision of the specimen during pancreaticoduodenectomy, the key surgical step of PD-L was longitudinal pancreaticojejunostomy in the remaining pancreas. Intraoperative blood loss in the PD-L group was lower than that in the PD group [ M(IQR)](300(200)ml vs. 500(500)ml, respectively; P<0.05). Similarly, hospitalization days(21.0(7.0)days vs. 25.0(8.5)days) and postoperative hospitalization days(13.0(8.0)days vs. 17.0(5.0) days) were also lower in the PD-L group compared to the PD group ( P<0.05). There were no significant differences in the operation time and postoperative complication rate between the two groups( P>0.05). In the PD-L group, the postoperative follow-up time was 5(5)months(range: 3 to 21 months). One case was lost for follow-up. Abdominal pain was relieved in 10 patients. Additionally, abdominal distension and steatosis were alleviated in 8 cases. Furthermore, 5 cases of diabetes mellitus showed improved control of HbA1c and fasting blood glucose levels after surgery. Conclusions:PD-L treatment can be used to treat chronic pancreatitis complicated by suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas. PD-L also has advantages in removing stones from the pancreatic duct and evaporation of pancreatic fluid. However, due to the single-center design and the small sample size of this study, further practice and long-term follow-up are still necessary.
7.Simultaneous content determination of eighteen nucleosides and free amino acids in Colla corii asini by UPLC-MS/MS
Shuai YANG ; Lin ZHENG ; Ming-Yan CHI ; Zi-Peng GONG ; Yue-Ting LI ; Mao-Chen WEI ; Yong HUANG
Chinese Traditional Patent Medicine 2024;46(7):2140-2146
AIM To establish a UPLC-MS/MS method for the simultaneous content determination of Asp,Guad,Adeno,Arg,Ade,Cyti,Phe,Leu,Ile,Glu,Ser,Gln,Gly,Ala,Hyp,Thr,Pro and Lys in Asini Corii Colla.METHODS The analysis was performed on a 45℃ thermostatic Waters BEH C18column(2.1 mm×50 mm,1.7 μm),with the mobile phase comprising of acetonitrile(containing 0.1% formic acid)-water flowing at 0.35 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive ion scanning with multiple reaction monitoring mode.Subsequently,chemical pattern recognition was performed by hierarchical clustering analysis,principal component analysis and orthogonal partial least squares-discriminant analysis.RESULTS Eighteen nucleosides and free amino acids showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 98.0%-104.9% with the RSDs of 1.6%-4.9% .Seventeen batches of samples were clustered into two categories,two principal components demonstrated the accumulative variance contribution rate of 60.75%,Leu,Phe,Ade and Guad were potential index constituents.CONCLUSION This stable and reliable method can be used for the quality control of Asini Corii Colla.
8.Effect of Zhenwu Decoction on electrical remodeling of cardiomyocytes in heart failure via I_(to)/Kv channels.
Chi CHE ; Xiao-Lin WANG ; Zhi-Yong CHEN ; Mei-Qun ZHENG ; Wei TANG ; Zong-Qiong LU ; Jia-Shuai GUO ; Wan-Qing HUANG ; Xin TIAN ; Lin LI
China Journal of Chinese Materia Medica 2023;48(13):3565-3575
This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.
Rats
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Animals
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Myocytes, Cardiac
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Atrial Remodeling
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Rats, Sprague-Dawley
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Heart Failure/metabolism*
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RNA, Messenger/metabolism*
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Potassium
9.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.
Xiao Shuai ZHANG ; Bing Cheng LIU ; Xin DU ; Yan Li ZHANG ; Na XU ; Xiao Li LIU ; Wei Ming LI ; Hai LIN ; Rong LIANG ; Chun Yan CHEN ; Jian HUANG ; Yun Fan YANG ; Huan Ling ZHU ; Ling PAN ; Xiao Dong WANG ; Gui Hui LI ; Zhuo Gang LIU ; Yan Qing ZHANG ; Zhen Fang LIU ; Jian Da HU ; Chun Shui LIU ; Fei LI ; Wei YANG ; Li MENG ; Yan Qiu HAN ; Li E LIN ; Zhen Yu ZHAO ; Chuan Qing TU ; Cai Feng ZHENG ; Yan Liang BAI ; Ze Ping ZHOU ; Su Ning CHEN ; Hui Ying QIU ; Li Jie YANG ; Xiu Li SUN ; Hui SUN ; Li ZHOU ; Ze Lin LIU ; Dan Yu WANG ; Jian Xin GUO ; Li Ping PANG ; Qing Shu ZENG ; Xiao Hui SUO ; Wei Hua ZHANG ; Yuan Jun ZHENG ; Qian JIANG
Chinese Journal of Hematology 2023;44(9):728-736
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
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Humans
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Adolescent
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Imatinib Mesylate/adverse effects*
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Incidence
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Antineoplastic Agents/adverse effects*
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Retrospective Studies
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Pyrimidines/adverse effects*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
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Treatment Outcome
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Benzamides/adverse effects*
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Leukemia, Myeloid, Chronic-Phase/drug therapy*
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Aminopyridines/therapeutic use*
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Protein Kinase Inhibitors/therapeutic use*
10.Impact of body mass index on perioperative efficacy and complications of robot-assisted radical cystectomy with intracorporeal urinary diversion
Shuai WANG ; Wei ZHENG ; Qijun WO ; Xiaolong QI ; Feng LIU ; Dahong ZHANG
Chinese Journal of Urology 2023;44(2):102-108
Objective:To determine the impact of body mass index (BMI) on perioperative and oncological outcomes after robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion.Methods:Clinical data of bladder cancer patients undergoing robot-assisted radical cystectomy with intracorporeal urinary diversion in Zhejiang Provincial People's Hospital from January 2017 to January 2020 were retrospectively analyzed. Patients were divided into three groups according to BMI, including 61 cases in normal group (<25.0 kg/m2), 52 cases in overweight group (25.0-29.9 kg/m2) and 33 cases in obese group (≥30.0 kg/m2). In the normal group, the median age was 73.6(59, 79), including 45 male(73.8%), with 51 cases(83.6%) of ASA score 0-2, 10 cases (16.4%)of 3 or higher, and 10 cases (16.4%) undergoing neoadjuvant chemotherapy. Past medical history included smoking in 34 cases (55.7%), hypertension in 19 cases (31.1%), diabetes in 10 cases (16.4%), heart disease in 12 cases (19.7%), and abdominal surgery in 6 cases (9.8%). In the overweight group, the median age was 69.7(60, 78), including 38 male (73.1%), with 25 cases (48.1%)of ASA score 0-2, 27 cases (51.9%) of 3 or higher, and 9 cases (17.3%) undergoing received neoadjuvant chemotherapy. Past medical history included smoking in 30 cases (57.7%), hypertension in 20 cases (38.5%), diabetes in 10 cases (19.2%), heart disease in 9 cases (17.3%), and abdominal surgery in 5 cases (9.6%). In the obses group, the median age was 69.9(61, 78), including 21 male(63.7%), with 20 cases (60.6%)of ASA score 0-2, 13 cases(39.4%) of 3 or higher, 9 cases (27.3%) undergoing neoadjuvant chemotherapy. Past medical history included smoking in 18 cases (54.5%), hypertension in 17 cases (51.5%), diabetes in 19 cases (57.6%), heart disease in 7 cases (21.2%), and abdominal surgery in 4 cases (12.1%). After statistical comparison among the three groups, it was found that the proportion of patients with hypertension and diabetes in the obesity group and overweight group was higher than that in the normal group (all P<0.05), but there was no significant difference in other factors (all P>0.05). During the surgical process, robot-assisted radical cystectomy and bilateral pelvic lymph node dissection were performed firstly. The scope of lymph node dissection was divided into standard range and expanded range, and the diversion was divided into orthotopic neobladder and ileal bladder. During the orthotopic neobladder process, 40-50 cm ileum at the distance of 15 cm away from ileocecum was obtained by stapler, and then the U-shaped neobladder was made, and the new bladder was anastomosed with urethra and bilateral ureter. For ileal bladder, the ileum was cut off 15cm away from the ileocecum with stapler to obtain the 15 cm ileum to prepare the ileal conduit and restore the continuity of the ileum. The bilateral ureteral spacing 3cm was implanted on the ileal conduit. In the normal group, standard range lymphatic dissection was performed in 20 cases (32.8%), enlarged dissection in 41 cases (67.2%), orthotopic neobladder in 22 cases(36.1%), and ileal conduit in 39 cases (63.9%). In the overweight group, standard range lymphatic dissection was performed in 12 cases (23.1%), enlarged dissection in 40 cases (76.9%), orthotopic neobladder in 26 cases (49.1%), and ileal conduit in 26 cases (50.9%). In the obesity group, the standard range of lymphatic dissection was performed in 7 cases (21.2%), enlarged dissection in 26 cases (78.7%), orthotopic neobladder in 7 cases (21.2%), and ileal conduit in 26 cases (78.8%). There was no significant difference among the three groups (all P>0.05). Compared the operation time, intraoperative blood loss, postoperative exhaust time, postoperative time of taking solid food, postoperative hospital stay, postoperative complications (according to the Clavien-Dindo grading system, postoperative complications are reported inⅠ-Ⅱ grade as mild complications and above Ⅲ grade as serious complications) and pathology results in three groups. Results:All cases successfully underwent robotically without conversion or major intraoperative complications. The operation time in overweight and obsess group were longer than that of normal group with RARC or orthotopic neobladder [310(250, 350) min, 370(310, 420) min, 250(230, 310) min, ( P<0.05)], but there was no significant difference in RARC and ileal conduit[270(220, 300) min, 280(230, 300) min, 240(220, 290)min, P>0.05]. The estimated blood loss in overweight and obsess group was more than that in normal group [230(150, 450)ml, 310(250, 600)ml, 190(100, 350)ml, P<0.05], but there was no difference in blood transfusion rate [4(7.7%), 2(6.1%), 5(8.2%), P>0.05]. The exhaust time [2(1, 3) days, 2(1, 4)days, 2(1, 4)days], postoperative solid food intake time [4(3, 5)days, 4(3, 6)days, 4(3, 6)days] and the hospital stay[10(5, 16)days, 10(6, 17)days, 12(6, 20)days] were not different in three groups(all P>0.05). The mild complication rates in 90 days were significant higher in overweight and obsess groups[28 (53.8%), 16(48.5%), 20(32.8%), P<0.05], but the total and severe complication rates were not significantly different. The incidences of urinary system complications and incision complications in obese and overweight patients were significantly higher than those in normal group ( P<0.05). There was no significant difference in the incidence of gastrointestinal complications and ureteral anastomosis-related complications (stricture or urinary leakage)( P>0.05). There was no significant difference in the number of dissected lymph node, positive lymph node, positive rate of incisional margin and postoperative pathological stage among three different BMI groups(all P>0.05). Conclusion:Robot-assisted radical cystectomy combined with intracorporeal urinary diversion is a safe and effective method for the treatment of overweight, obese and even morbidly obese patients with bladder cancer. The recovery of intestinal function and the oncological results are not affected by body mass index. However, laparoscopic radical cystectomy for overweight and obese patients, especially for orthotopic neobladder, has the risk of long operation time, large amount of intraoperative bleeding and increased risk of minor postoperative complications.

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