1.Preparation of vitexin albumin nanoparticles and its pharmacokinetic study.
Xue ZHANG ; Qiang WANG ; Jian-Quan PAN ; Si-Wei WANG ; Cheng-Yuan WU ; Yun-Na CHEN ; Feng-Ling WANG ; Lei WANG ; Wei-Dong CHEN
China Journal of Chinese Materia Medica 2023;48(19):5205-5215
This study aims to prepare vitexin albumin nanoparticles(VT-BSA-NPs) to alleviate the low bioavailability of vitexin(VT) in vivo due to its poor water solubility. VT micro powders were prepared by the antisolvent crystallization method, and the morphology, size, and physicochemical properties of VT micro powders were studied. The results showed that the VT micro powder had a particle size of(187.13±7.15) nm, an approximate spherical morphology, and a uniform size distribution. Compared with VT, the chemical structure of VT micro powders has not changed. VT-BSA-NPs were prepared from VT micro powders by desolvation-crosslinking curing method. The preparation process was screened by single factor test and orthogonal test, and the quality evaluation of the optimal prescription particle size, PDI, Zeta potential, EE, and morphology was performed. The results showed that the average particle size of VT-BSA-NPs was(124.33±0.47) nm; the PDI was 0.184±0.012; the Zeta potential was(-48.83±2.20) mV, and the encapsulation rate was 83.43%±0.39%, all of which met the formulation-related requirements. The morphological results showed that the VT-BSA-NPs were approximately spherical in appearance, regular in shape, and without adhesion on the surface. In vitro release results showed a significantly reduced release rate of VT-BSA-NPs compared with VT, indicating a good sustained release effect. LC-MS/MS was used to establish an analytical method for in vivo analysis of VT and study the plasma pharmacokinetics of VT-BSA-NPs in rats. The results showed that the specificity of the analytical method was good, and the extraction recovery was more than 90%. Compared with VT and VT micro powders, VT-BSA-NPs could significantly increase AUC, MRT, and t_(1/2), which was beneficial to improve the bioavailability of VT.
Rats
;
Animals
;
Serum Albumin, Bovine/chemistry*
;
Chromatography, Liquid
;
Tandem Mass Spectrometry
;
Nanoparticles/chemistry*
;
Particle Size
;
Drug Carriers/chemistry*
2.Research Progress of Post-Transplant Cyclophosphamide Combined with Antithymocyte Globulin in Preventing GVHD after Hematopoietic Stem Cell Transplantation --Review.
Journal of Experimental Hematology 2023;31(6):1899-1904
Graft-versus-host disease (GVHD) is one of the major complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which seriously affects the prognosis of patients. At present, a new regimen of post-transplantation cyclophosphamide (PTCy) combined with antithymocyte globulin (ATG) has been used to prevent GVHD, indicating that PTCy combined with ATG may have a good effect on the prevention of GVHD in different types of transplantation. However, the mechanism of this regimen, its effect on immune reconstitution and viral reactivation still needs to be further studied. Therefore, this article briefly reviews the research progress of PTCy combined with ATG in preventing GVHD after HSCT.
Humans
;
Antilymphocyte Serum
;
Cyclophosphamide
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
Graft vs Host Disease/prevention & control*
;
Transplantation, Homologous
;
Retrospective Studies
3.Prognostic value of a predictive model comprising preoperative inflammatory response and nutritional indexes in patients with gastric cancer.
Liang Liang WU ; Ming Zhi CAI ; Bao Gui WANG ; Jing Yu DENG ; Bin KE ; Ru Peng ZHANG ; Han LIANG ; Xiao Na WANG
Chinese Journal of Gastrointestinal Surgery 2023;26(7):680-688
Objective: To investigate the prognostic value of preoperative inflammatory and nutritional condition detection in the postoperative survival, and establish a prognostic model for predicting the survival of patients with gastric cancer. Methods: The clinicopathological data of 1123 patients with gastric cancer who had undergone radical gastrectomy in Tianjin Medical University Cancer Institute & Hospital from January 2005 to December 2014 were retrospectively analyzed. Patients with history of other malignancy, with history of gastrectomy, who had received preoperative treatment, who died during the initial hospital stay or first postoperative month, and missing clinical and pathological information were excluded. Cox univariate and multivariate analyses were used to identify independent clinicopathological factors associated with the survival of these gastric cancer patients. Cox univariate analysis was used to identify preoperative inflammatory and nutritional indexes related to the survival of patients with gastric cancer after radical gastrectomy. Moreover, the Cox proportional regression model for multivariate survival analysis (forward stepwise regression method based on maximum likelihood estimation) was used. The independent clinicopathological factors that affect survival were incorporated into the following three new prognostic models: (1) an inflammatory model: significant preoperative inflammatory indexes identified through clinical and univariate analysis; (2) a nutritional model: significant preoperative nutritional indexes identified through clinical and univariate analysis; and (3) combined inflammatory/nutritional model: significant preoperative inflammatory and nutritional indexes identified through clinical and univariate analysis. A model that comprised only pT and pN stages in tumor TNM staging was used as a control model. The integrated area under the receiver operating characteristic curve (iAUC) and C-index were used to evaluate the discrimination of the model. Model fitting was evaluated by Akaike information criterion analysis. Calibration curves were used to assess agreement between the predicted probabilities and actual probabilities at 3-year or 5-year overall survival (OS). Results: The study cohort comprised 1 123 patients with gastric cancer. The mean age was 58.9±11.6 years, and 783 were males. According to univariate analysis, age, surgical procedure, extent of lymph node dissection, tumor location, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and nerve invasion were associated with 5-year OS after radical gastrectomy for gastric cancer (all P<0.050). Multivariate analysis further identified age (HR: 1.18, 95%CI: 1.03-1.36, P=0.019), maximum tumor size (HR: 1.19, 95%CI: 1.03-1.38, P=0.022), number of examined lymph nodes (HR: 0.79, 95%CI: 0.68-0.92, P=0.003), pT stage (HR: 1.40, 95%CI: 1.26-1.55, P<0.001) and pN stage (HR: 1.28, 95%CI: 1.21-1.35, P<0.001) as independent prognostic factors for OS of gastric cancer patients. Additionally, according to univariate survival analysis, the preoperative inflammatory markers of neutrophil count, percentage of neutrophils, neutrophil/lymphocyte ratio, platelet/neutrophil ratio and preoperative nutritional indicators of serum albumin and body mass index were potential prognostic factors for gastric cancer (all P<0.05). On the basis of the above results, three models for prediction of prognosis were constructed. Variables included in the three models are as follows. (1) Inflammatory model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, and neutrophil-lymphocyte ratio; (2) nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and serum albumin; and (3) combined inflammatory/nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, neutrophil-lymphocyte ratio, and serum albumin. We found that the predictive accuracy of the combined inflammatory/nutritional model, which incorporates both inflammatory indicators and nutrition indicators (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.698),was superior to that of the inflammation model (iAUC: 0.662, 95% CI: 0.673-0.706;C-index: 0.675), nutritional model (iAUC: 0.666, 95% CI: 0.642-0.698, C-index: 0.672), and TNM staging control model (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.658). Furthermore, the combined inflammatory/nutritional model had better fitting performance (AIC: 10 762) than the inflammatory model (AIC: 10 834), nutritional model (AIC: 10 810), and TNM staging control model (AIC: 10 974). Conclusions: Preoperative percentage of neutrophils, NLR, and BMI have predictive value for the prognosis of gastric cancer patients. The inflammatory / nutritional model can be used to predict the survival and prognosis of gastric cancer patients on an individualized basis.
Male
;
Humans
;
Middle Aged
;
Aged
;
Female
;
Prognosis
;
Retrospective Studies
;
Stomach Neoplasms/pathology*
;
Neoplasm Staging
;
Gastrectomy
;
Serum Albumin
4.Pharmacogenetic testing improves treatment responses in patients with PLA2R-related membranous nephropathy.
Tingting TAN ; Yihou ZHENG ; Yun LI ; Youjia ZENG
Journal of Southern Medical University 2023;43(6):1047-1050
OBJECTIVE:
To evaluate the value of pharmacogenetic testing for improving the efficacy and safety of treatment with cyclosporine, tacrolimus, and cyclophosphamide (CTX) for PLA2R-related membranous nephropathy and for determing individualized and precise treatment plans for the patients.
METHODS:
A total of 63 patients with PLA2R-related membranous nephropathy hospitalized in the Department of Nephrology at our hospital from January, 2019 to October, 2021 were enrolled in this study. Thirty-three of the patients underwent pharmacogenetic testing before taking the immunosuppressive drugs selected based on the results of genetic screening for sensitive targets, and the other 30 patients were empirically given immunosuppressive drugs according to the guidelines (control group). The clinical efficacy and adverse effects of the immunosuppressive drugs were analyzed for all the patients. The two groups of patients were compared for demographic and biochemical parameters including 24-h urine protein, serum albumin, renal function, and serum anti-phospholipase A2 receptor antibody both before and at 3 months after the beginning of the treatment.
RESULTS:
Among the 33 patients undergoing pharmacogenetic testing, 51.5% showed a GG genotype for cyclosporine, and 61.6% had an AG genotype for tacrolimus; for CTX, 51.5% of the patients showed a homozygous deletion and 63.6% had an AA genotype. After treatment for 3 months, serum anti-phospholipase A2 receptor antibody, 24-h urine protein, and serum albumin levels were significantly improved in pharmacogenetic testing group as compared with the control group (P < 0.05).
CONCLUSION
Individualized and precise administration of immunosuppressive drugs based on pharmacogenetic testing better controls proteinuria and serum antiphospholipase A2 receptor antibodies and increases serum albumin level in patients with PLA2R-related membranous nephropathy.
Humans
;
Autoantibodies
;
Cyclosporine/therapeutic use*
;
Glomerulonephritis, Membranous/diagnosis*
;
Homozygote
;
Immunosuppressive Agents/therapeutic use*
;
Pharmacogenomic Testing
;
Receptors, Phospholipase A2
;
Sequence Deletion
;
Serum Albumin
;
Tacrolimus/therapeutic use*
5.Diagnosis and treatment of 26 cases of adenovirus infection after allogeneic hematopoietic stem cell transplantation.
Fei ZHOU ; Su Ning CHEN ; De Pei WU ; Xue Feng HE
Chinese Journal of Hematology 2023;44(4):302-307
Objective: To analyze the clinical characteristics and prognosis of adenovirus infection after allogeneic hematopoietic stem cell transplantation. Methods: A total of 26 patients with adenovirus infection admitted to the posttransplant ward of the First Affiliated Hospital of Soochow University from 2018 to 2022 were enrolled. Their data on baseline and clinical characteristics, treatment, and follow-up were analyzed. Results: The median patient age was 30 (22, 44) years. Twenty-two patients received related haploid stem cell transplantation, three received unrelated stem cell transplantation, and one received umbilical cord stem cell transplantation. Antithymocyte globulin was included in the conditioning regimen in 25 patients. The median time of adenovirus infection was +95 (+44, +152) days. The median peripheral blood lymphocyte count was 0.30 (0.11, 0.69) × 10(9)/L. Twelve patients had acute graft-versus-host disease. Twenty-four patients received antirejection therapies at diagnosis. Sixteen cases had combined infection with other pathogens with adenovirus infection. Eight cases were diagnosed as asymptomatic infection, and 18 were diagnosed as adenovirus disease, including pneumonia (38.89% ) , gastrointestinal disease (38.89% ) , encephalitis (33.33% ) , hepatitis (5.56% ) , and urinary tract inflammation (5.56% ) . The age of >30 years was a risk factor for adenovirus disease (P=0.03) . Eighteen patients received tapering of immunosuppression, and all 26 patients received at least one antiviral drug. Other treatments included high-dose gamma globulin and donor lymphocyte infusion. Adenovirus infection improved in 10 cases and progressed in 16 cases. The median follow-up time was 30 (7, 237) days. Twenty-two patients died. The all-cause mortality rate was (88.5±7.1) % , and the attributable mortality rate was 45.5% . There was no significant difference in the 100 d survival rate between asymptomatic infected patients and patients diagnosed with adenovirus disease (37.5% vs 22.2% , HR=1.83, 95% CI 0.66-5.04, P=0.24) . Conclusion: The age of >30 years was a risk factor for adenovirus disease. Mortality was high in patients with adenovirus infection after allogeneic hematopoietic stem cell transplantation.
Humans
;
Adult
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
Graft vs Host Disease/etiology*
;
Antilymphocyte Serum/therapeutic use*
;
Transplantation, Homologous/adverse effects*
;
Adenoviridae Infections/therapy*
;
Transplantation Conditioning/adverse effects*
;
Retrospective Studies
6.Expert consensus on the use of human serum albumin in adult cardiac surgery.
Fei XIANG ; Fuhua HUANG ; Jiapeng HUANG ; Xin LI ; Nianguo DONG ; Yingbin XIAO ; Qiang ZHAO ; Liqiong XIAO ; Haitao ZHANG ; Cui ZHANG ; Zhaoyun CHENG ; Liangwan CHEN ; Jimei CHEN ; Huishan WANG ; Yingqiang GUO ; Nan LIU ; Zhe LUO ; Xiaotong HOU ; Bingyang JI ; Rong ZHAO ; Zhenxiao JIN ; Robert SAVAGE ; Yang ZHAO ; Zhe ZHENG ; Xin CHEN
Chinese Medical Journal 2023;136(10):1135-1143
7.Frailty prevalence and its associations in a subacute geriatric ward in Singapore.
Christine Yuanxin CHEN ; Thulasi CHANDRAN ; Vivian Cantiller BARRERA ; Rachelle Tumbokon TAN-PANTANAO ; Tanya Joy Zapata QUICHO ; Zin Tun THANT ; Kiat Sern GOH
Singapore medical journal 2023;64(3):196-202
INTRODUCTION:
Our aim was to study the prevalence of frailty and its associated factors in a subacute geriatric ward.
METHODS:
This was a cross-sectional study of 167 participants between June 2018 and June 2019. Baseline demographics and participants' Mini Nutritional Assessment, Geriatric Depression Scale, Mini Mental State Examination, Charlson's Comorbidity Index and LACE index scores were obtained. Functional measurements such as modified Barthel's Index scores and hand grip strength (HGS) were taken. Frailty was assessed using the Clinical Frailty Scale (CFS) and the FRAIL scale. Data on history of healthcare utilisation, medications, length of stay, selected blood investigations and presence of geriatric syndromes were also collected.
RESULTS:
The prevalence of pre-frailty (CFS 4) and frailty (CFS ≥ 5) was 16.2% and 63.4%, respectively. There were significant associations between CFS and age (pre-frail vs. non-frail: odds ratio [OR] 1.14, 95% confidence interval [CI] 1.04-1.25, P = 0.006; frail vs. non-frail: OR 1.08, 95% CI 1.01-1.15, P = 0.021), HGS at discharge (frail vs. non-frail: OR 0.90, 95% CI 0.82-0.99, P = 0.025), serum albumin (frail vs. non-frail: OR 0.90, 95% CI 0.82-0.99, P = 0.035) and the presence of urinary incontinence (frail vs. non-frail: OR 3.03, 95% CI 1.19-7.77, P = 0.021).
CONCLUSION
Frailty is highly prevalent in the subacute geriatric setting and has many associated factors. In this study, independent factors associated with frailty were age, HGS at discharge, serum albumin and urinary incontinence. This has implications for future resource allocation for frail older inpatients and may help direct further research to study the effectiveness of frailty-targeted interventions.
Humans
;
Aged
;
Frailty/epidemiology*
;
Frail Elderly
;
Hand Strength
;
Prevalence
;
Singapore/epidemiology*
;
Cross-Sectional Studies
;
Fatigue Syndrome, Chronic
;
Geriatric Assessment
;
Urinary Incontinence
;
Serum Albumin
8.Mediation of serum albumin in the association of serum potassium with mortality in Chinese dialysis patients: a prospective cohort study.
Naya HUANG ; Yuanying LIU ; Zhen AI ; Qian ZHOU ; Haiping MAO ; Xiao YANG ; Yuanwen XU ; Xueqing YU ; Wei CHEN
Chinese Medical Journal 2023;136(2):213-220
BACKGROUND:
The clinical importance of hypokalemia is likely underrecognized in Chinese dialysis patients, and whether its clinical effect was mediated by serum albumin is not fully elucidated. This study aimed to explore the association between serum potassium and mortality in dialysis patients of a Chinese nationwide multicenter cohort, taking albumin as a consideration.
METHODS:
This was a prospective nation-wide multicenter cohort study. Restricted cubic splines were used to test the linearity of serum potassium and relationships with all-cause (AC) and cardiovascular (CV) mortality and a subsequent two-line piecewise linear model was fitted to approach the nadir. A mediation analysis was performed to examine relations of albumin to potassium and mortalities.
RESULTS:
A total of 10,027 patients were included, of whom 6605 were peritoneal dialysis and 3422 were hemodialysis patients. In the overall population, the mean age was 51.7 ± 14.8 years, 55.3%(5546/10,027) were male, and the median dialysis vintage was 13.60 (4.70, 39.70) months. Baseline serum potassium was 4.30 ± 0.88 mmol/L. After a median follow-up period of 26.87 (14.77, 41.50) months, a U-shape was found between potassium and mortality, and a marked increase in risk at lower potassium but a moderate elevation in risk at higher potassium were observed. The nadir for AC mortality risk was estimated from piecewise linear models to be a potassium concentration of 4.0 mmol/L. Interestingly, the significance of the association between potassium and mortality was attenuated when albumin was introduced into the extended adjusted model. A subsequent significant mediation by albumin for potassium and AC and CV mortalities were found ( P < 0.001 for both), indicating that hypokalemia led to higher mortality mediated by low serum albumin, which was a surrogate of poor nutritional status and inflammation.
CONCLUSIONS
Associations between potassium and mortalities were U-shaped in the overall population. The nadir for AC mortality risk was at a potassium of 4.0 mmol/L. Serum albumin mediated the association between potassium and AC and CV mortalities.
Adult
;
Aged
;
Female
;
Humans
;
Male
;
Middle Aged
;
East Asian People
;
Hypokalemia/etiology*
;
Kidney Failure, Chronic/mortality*
;
Potassium/blood*
;
Prospective Studies
;
Renal Dialysis
;
Serum Albumin/analysis*
9.Short-term efficacy of dapagliflozin in children with hereditary proteinuric kidney disease.
Jing Yi CUI ; Jiao Jiao LIU ; Xiao Yan FANG ; Jing CHEN ; Yi Hui ZHAI ; Hong XU ; Qian SHEN
Chinese Journal of Pediatrics 2023;61(2):164-168
Objective: To explore the short-term efficacy and safety of dapagliflozin in children with hereditary proteinuric kidney disease. Methods: This was a prospective cohort study. From August 2020 to December 2021, 23 children with hereditary kidney disease from Children's Hospital of Fudan University were enrolled. Patients received dapagliflozin 5 mg/d (weight≤30 kg) or initial dose 5 mg/d for 1 week, then 10 mg/d (weight>30 kg) and the dose of angiotensin converting enzyme inhibitors was stable during treatment. Clinical data including demographic parameters, primary diagnosis, estimated glomerular filtration rate (eGFR), 24 h proteinuria and characteristics in the follow-up were collected. The primary outcome was the change in 24 h proteinuria at 12 (±2) weeks, secondary outcomes included changes of 24 h proteinuria at 24 (±2) weeks, eGFR at both 12 (±2) and 24 (±2) weeks. The data were analysed by using mixed linear model. Results: Totally 23 patients were enrolled, including 16 males and 7 females. The age was (10.8±2.9) years. The primary diseases were Alport syndrome (12 cases), Dent disease (5 cases), proteinuria (4 cases), and focal segmental glomerulosclerosis (2 cases) respectively. Primary outcome showed that 24 h proteinuria decreased from baseline at 12 (±2) weeks during treatment (1.75 (1.46, 2.20) vs. 1.84 (1.14, 2.54) g/m2, P<0.05). Secondary outcomes showed that there was no significant difference in 24 h urine protein at 24 (±2) weeks (P>0.05). eGFR decreased slightly at 12 (±2) weeks ((107±21) vs. (112±28) ml/(min·1.73m2), P<0.05), and there was no significant difference at 24 (±2) weeks (P>0.05). Serum albumin increased at 12 (±2) and 24 (±2) weeks following the treatment ((39±8) vs. (37±8) g/L, (38±7) vs. (37±8) g/L, both P<0.05). No hypoglycemia event was reported during the treatment. Conclusion: The dapagliflozin had therapeutic effects on decreasing proteinuria and increasing serum albumin in short-term treatment in children with hereditary proteinuric kidney disease, no hypoglycemia or serious adverse events were observed.
Female
;
Male
;
Humans
;
Child
;
Adolescent
;
Prospective Studies
;
Nephritis, Hereditary
;
Proteinuria/drug therapy*
;
Serum Albumin
10.Impact of immunosuppression intensified conditioning regimen for patients with strong positive pre-transplantation donor-specific anti-HLA antibodies (DSAs) undergoing haploidentical hematopoietic stem cell transplantation.
Hui Xia LIU ; Dao Lin WEI ; Shan SHAO ; Ying JIANG ; Shu LI ; Jun ZHU ; Chun WANG ; Chu Xian ZHAO
Chinese Journal of Hematology 2023;44(8):654-659
Objective: To explore the efficacy of immunosuppression intensified conditioning regimen in patients who have strongly positive donor-specific Anti-HLA antibodies (DSAs) and received a haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Clinical data of 10 patients with strongly positive pretransplant DSAs (defined as MFI ≥10000) were retrospectively analyzed in this study. All of them received a haplo-HSCT in the Hematology Department of Shanghai Zhaxin Traditional Chinese & Western Medicine Hospital. Results: ① Of all ten patients, three were males, and seven were females, with a median age of 53.5 (36-64) years. Of the 10 patients, three were diagnosed with acute myeloid leukemia, two were myelodysplastic syndromes (MDS), two were chronic myelomonocytic leukemia (CMML), two were in an accelerated phase of chronic myeloid leukemia (CML-AP), and one was primary myelofibrosis (PMF). ② Conditioning regimen consisted of fludarabine (Flu) /busulfan (Bu) combined with whole-body irradiation (TBI) /cyclophosphamide (Cy). ③ On the seventh day after transplantation, the median pretransplant DSA level was MFI 15 999 (10 210-23 417) and 10 787 (0-22 720). ④ Eight patients acquired hematopoietic reconstitution; the median time of neutrophil engraftment was 14 (10-16) days; and 18 (14-20) days for platelet engraftment. After a median follow-up of 12.5 (1.5-27) months, primary graft failure was found in one patient and another with poor graft function. Seven patients remained in a disease remission state, and all were DSA-negative. Conclusions: An intensified immunosuppression conditioning regimen can efficiently decrease the level of donor-specific anti-HLA antibodies (DSAs), leading to good short-term efficacy.
Male
;
Female
;
Humans
;
Middle Aged
;
Retrospective Studies
;
Graft vs Host Disease
;
Transplantation Conditioning
;
China
;
Hematopoietic Stem Cell Transplantation
;
Antilymphocyte Serum
;
Busulfan
;
Cyclophosphamide/therapeutic use*
;
Immunosuppression Therapy

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