1.Study on the clinical effect of initiating continuous blood purification at different times for severe acute pancreatitis
Feiyang CHEN ; Ruoyu XIE ; Xiaotong HAN ; Fengling NING ; Yun CHEN ; Huimin LIU ; Lilei LIU ; Xiang LI
Chinese Critical Care Medicine 2024;36(9):937-942
Objective:To observe the clinical effect of initiating continuous blood purification (CBP) treatment at different times for patients with severe acute pancreatitis (SAP), and to explore the optimal timing for starting CBP treatment for SAP, so as to provide evidence for clinicians to start CBP treatment.Methods:A retrospective cohort study was used to select patients with SAP who received CBP treatment in People's Hospital of Hunan Province from January 2020 to December 2023. According to the timing of CBP initiation, the patients were divided into early initiation group (diagnosis of SAP to the first CBP treatment time < 24 hours) and late initiation group (diagnosis of SAP to the first CBP treatment time of 24-48 hours). The general data, acute physiology and chronic health evaluationⅡ(APACHEⅡ), bedside index for severity in acute pancreatitis (BISAP) score and laboratory indicators, local complications and systemic complications, intensive care unit (ICU) treatment time, hospital stay, treatment cost, and clinical outcome of the two groups were collected and compared.Results:A total of 130 patients with SAP who received CBP treatment were enrolled, including 90 patients in the early initiation group and 40 patients in the late initiation group. Before treatment, there were no significant differences in gender, age, APACHEⅡscore, BISAP score, etiology and laboratory examination indexes between the early initiation group and late initiation group. At 48, 72, 96 hours after treatment, the blood calcium level of the two groups was significantly higher than that before treatment, and the levels of white blood cell count (WBC), C-reactive protein (CRP), lactic acid, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), APACHEⅡscore and BISAP score were significantly lower than those before treatment. The WBC level, APACHEⅡscore and BISAP score of the late initiation group were significantly lower than those of the early initiation group at 72 hours and 96 hours after treatment [WBC (×10 9/L): 10.96 (8.68, 13.04) vs. 12.45 (8.93, 16.30) at 72 hours after treatment, and 10.18 (8.68, 12.42) vs. 11.96 (8.81, 16.87) at 96 hours after treatment; APACHEⅡscore: 9.50 (5.75, 12.00) vs. 11.00 (6.25, 14.00) at 72 hours after treatment, and 10.00 (4.00, 12.00) vs. 12.00 (7.00, 14.75) at 96 hours after treatment; BISAP score: 2.35±1.03 vs. 2.76±1.10 at 72 hours after treatment, and 2.08±1.21 vs. 2.70±1.11 at 96 hours after treatment], the differences were statistically significant (all P < 0.05). In terms of complications, the incidence of pancreatic abscess in the late initiation group was significantly lower than that in the early initiation group [5.00% (2/40) vs. 20.00% (18/90)], but the incidence of abdominal compartment syndrome was significantly higher than that in the early initiation group [42.50% (17/40) vs. 13.33% (12/90)], the differences were statistically significant (all P < 0.05). In addition, the ICU treatment time in the early initiation group was significantly shorter than that in the late initiation group [days: 11.00 (6.00, 20.00) vs. 15.00 (9.75, 25.00), P < 0.05], and there were no statistically significant differences in hospitalization costs, length of stay and mortality between the two groups. Conclusions:CBP can effectively increase the level of blood calcium and decrease the level of lactic acid and inflammatory factors. Starting CBP within 24-48 hours after diagnosis of SAP can reduce WBC level and disease severity score faster, and reduce the occurrence of pancreatic abscess. Initiation of CBP within 24 hours after diagnosis of SAP can reduce the incidence of abdominal compartment syndrome and shorten the duration of ICU treatment.
2.Exploring the Generation and Academic Significance of the Nineteen New Pathogenic Factors Based on Zhou Zhongying's Ac-ademic Idea of"Identifying the Core Pathogenesis"
Ke LIU ; Pengfei XIE ; Huifang GUAN ; Qingwei LI ; Xiuyang LI ; Xiaotong YU ; Xiaolin TONG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(1):1-5
This article explores the application of Professor Zhou Zhongying's"focus on the core pathogenesis"concept in the con-text of epidemic hemorrhagic fever and examines how Academician Tong Xiaolin has inherited and developed Professor Zhou's experi-ences.Influenced by Professor Zhou Zhongying's academic thoughts and considering the contemporary context,Academician Tong Xia-olin,drawing on years of clinical experience,has proposed a new set of Nineteen Pathogenic Factors.Building upon the foundation of the Nineteen Pathogenic Factors in the The Yellow Emperor's Inner Classic,this new framework enriches and expands the understanding of disease location,etiology and pathogenesis,disease classification,and pays attention to a comprehensive understanding of diseases.It emphasizes that the process of seeking the underlying mechanisms should be approached from three aspects:dynamic,state,and condition,rather than solely focusing on the immediate clinical manifestations.This comprehensive approach to understand-ing disease development offers a fresh perspective and contributes to the application of traditional Chinese Medicine in the diagnosis and treatment of modern diseases.
3.Clinical analysis of seven cases of primary hyperoxaluria type 1
Zuolin LI ; Bin WANG ; Fengmei WANG ; Haifeng NI ; Yuqiu LIU ; Wen SHI ; Junlan YANG ; Xiaotong XIE ; Bicheng LIU ; Xiaoliang ZHANG
Chinese Journal of Internal Medicine 2024;63(8):781-786
We retrospectively analyzed the clinical data of seven patients (four men and three women) with primary hyperoxaluria (PH) type 1 (PH1) in the Department of Nephrology of Zhongda Hospital, Southeast University from January 2018 to October 2023. The mean age at disease onset was 32.1 (range: 26-42) years. The mean age at diagnosis was 40.6 (range: 28-51) years. All patients initially had kidney stones, and three patients were found to have renal insufficiency at the time of disease onset. Among them, two patients underwent hemodialysis immediately. Symptoms at the first visit included bone pain ( n=7), joint pain or deformity ( n=5), fatigue ( n=5), hypotension ( n=3), and subcutaneous nodules ( n=2). Four patients had a family history of PH. All patients had varying degrees of anemia (60-114 g/L), significant hypoalbuminemia (16.5-32.1 g/L), and hypercoagulable state (D-dimer: 2 230-12 781 μg/L). Seven patients received maintenance hemodialysis; their mean age was 37.7 (range: 26-50) years. The mean duration from disease onset to hemodialysis was 5.6 (range: 0-20) years. Five patients repeatedly experienced dialysis access dysfunction. Three patients underwent kidney transplantation before a diagnosis was made, and all transplanted kidneys lost function due to oxalate deposition. The mean follow-up duration was 14.43 (range: 4-38) months. Unfortunately, one patient died. All seven patients underwent computed tomography of the abdomen. All patients suffered skeletal abnormalities, bilateral nephrolithiasis, and nephrocalcinosis. Six patients carried AGXT gene mutations, including four compound heterozygous mutations and two pure homozygous mutations.The mutation sites included: c.823-824dup.AG (p.S275Rfs*38)(exon 8), c.815-816ins.GA (p.S275Rfs*38)(exon 8), c.595G>A (p.G199S) (exon 5), c.32C>G (p.P11R) (exon 1), and c.638C>T (p.A213V)(exon 6). According to the American College of Medical Genetics and Genomics guidelines, two loci were identified as likely pathogenic variants, seven were identified as pathogenic variants, and one locus was identified as having uncertain significance. In addition, patients 1 and 4 underwent skin biopsy, patient 2 underwent renal transplant biopsy, and patient 3 underwent bone marrow biopsy. Interestingly, significant oxalate deposition was found in the tissues. Therefore, PH1 is a rare autosomal recessive inherited disease. This study not only enhanced the understanding of the clinical characteristics of PH1 patients but also had great significance in early diagnosis and treatment of the disease.
4.Characterization of 19 novel gene mutation sites associated with autosome-dominant polycystic kidney disease
Junlan YANG ; Siqi PENG ; Zhiyuan WEI ; Jianan JIANG ; Bin WANG ; Fengmei WANG ; Xiaotong XIE ; Tian XU ; Xiaoliang ZHANG
Chinese Journal of Internal Medicine 2024;63(9):866-873
By analyzing the of genetic testing data of patients with renal polycystic kidney disease and their relatives, this study aims to identify unreported novel gene mutation sites associated with autosomal dominant polycystic kidney disease (ADPKD). Structural prediction software was employed to investigate protein structural changes before and after mutations, explore genotype-phenotype correlations, and enrich the ADPKD gene database. In this single-center retrospective study, patients with multiple renal cysts diagnosed from January 2019 to February 2023 at the Zhong Da Hospital Southeast University were included. Genetic and clinical data of patients and their families were collected. Unreported novel gene mutation sites associated with ADPKD were identified. The AlphaFold v2.3.1 software was used to predict protein structures. Changes in protein structure before and after mutations were compared to explore genotype-phenotype correlations and enrich the ADPKD gene database. Twelve mutated genes associated with renal cysts were detected in 52 families. Nineteen novel gene mutation sites associated with ADPKD were identified, including 17 mutations in the PKD1 gene (one splicing mutation, seven frameshift mutations, four nonsense mutations, one whole-codon insertion, and four missense mutations); one ALG9 missense mutation; and one chromosomal structural variation. Truncating mutations in the PKD1 gene were correlated with a more severe clinical phenotype, while non-truncating mutations were associated with greater clinical heterogeneity. Numerous novel gene mutation sites associated with ADPKD remain unreported. Therefore, it is essential to analyze the pathogenicity of these novel mutation sites, establish genotype-phenotype correlations, and enrich the ADPKD gene database.
5.Solubilization techniques used for poorly water-soluble drugs.
Bing XIE ; Yaping LIU ; Xiaotong LI ; Pei YANG ; Wei HE
Acta Pharmaceutica Sinica B 2024;14(11):4683-4716
About 40% of approved drugs and nearly 90% of drug candidates are poorly water-soluble drugs. Low solubility reduces the drugability. Effectively improving the solubility and bioavailability of poorly water-soluble drugs is a critical issue that needs to be urgently addressed in drug development and application. This review briefly introduces the conventional solubilization techniques such as solubilizers, hydrotropes, cosolvents, prodrugs, salt modification, micronization, cyclodextrin inclusion, solid dispersions, and details the crystallization strategies, ionic liquids, and polymer-based, lipid-based, and inorganic-based carriers in improving solubility and bioavailability. Some of the most commonly used approved carrier materials for solubilization techniques are presented. Several approved poorly water-soluble drugs using solubilization techniques are summarized. Furthermore, this review summarizes the solubilization mechanism of each solubilization technique, reviews the latest research advances and challenges, and evaluates the potential for clinical translation. This review could guide the selection of a solubilization approach, dosage form, and administration route for poorly water-soluble drugs. Moreover, we discuss several promising solubilization techniques attracting increasing attention worldwide.
6.Treatment strategy of calciphylaxis in dialysis patients
Yuqiu LIU ; Xiaotong XIE ; Hong LIU ; Xiaoliang ZHANG
Chinese Journal of Nephrology 2023;39(5):393-397
Calciphylaxis is a vascular disease caused by a combination of multiple factors, and the calcified ischemic lesion results in the severe skin damage accompanied by unbearable pain. Calciphylaxis tends to occur in patients with end-stage renal disease, and the treatment of this disease faces enormous challenges. Current treatment recommendations are mainly based on clinical experience and observational research reports, and there is still a lack of clinical practice standards or consensus for managing calciphylaxis. Therefore, this paper will review the effective treatment methods and off-label use of calciphylaxis based on literature reports, providing reference for the clinical treatment of the disease.
7.Examination of Quality Characteristics of Rehmannia glutinosa Leaves by Different Fixation Methods Based on Fingerprint and Antioxidant Activity
Jinpeng CUI ; Xiaotong GENG ; Mengjuan CHENG ; Weifeng LI ; Juan ZHANG ; Qingpu LIU ; Jingwei LEI ; Caixia XIE
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(23):197-204
ObjectiveTo analyze the effect of different fixation methods on the chemical quality characteristics and antioxidant activity of Rehmannia glutinosa leaves, so as to lay a foundation for the selection of processing technology and quality evaluation of this medicinal materials. MethodR. glutinosa leaves was dried at 55 ℃ after treating by three fixation methods (55 ℃, boiling water, 105 ℃), and then the fingerprints of R. glutinosa leaves were collected by high performance liquid chromatography (HPLC) and near infrared spectroscopy (NIRS), and their antioxidant activities were analyzed by the 2,2-biphenyl-1-picrylhydrazyl (DPPH) method. Finally, similarity analysis, principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA) and Pearson correlation analysis were used to comprehensively evaluate the quality of R. glutinosa leaves with different fixation methods. ResultThe results of HPLC and NIRS fingerprint analysis indicated that there were differences in the quality characteristics of R. glutinosa leaves by different fixation treatments. The comprehensive score of chemical quality of R. glutinosa leaves by fixation at 55 ℃ was the highest, its average comprehensive score was 2.096, followed by fixation at 105 ℃, and the lowest was fixation with boiling water. The antioxidant activity of sample with fixation at 55 ℃ was the highest, followed by fixation with boiling water. The results of OPLS-DA showed that verbascoside, isoacteoside and catalpol were the main components causing the difference in chemical quality of the leaves from the three treatments, and the three components were positively correlated with the antioxidant activity of R. glutinosa leaves. Among them, the correlation between verbascoside and antioxidant activity was extremely significant, and the isoacteoside was significant. ConclusionThe chemical quality and antioxidant activity of R. glutinosa leaves are affected by the method of fixation, and the fixation at low temperature is the best primary processing method of R. glutinosa leaves.
8.Analysis of Characteristics of Volatile Organic Compounds and Bacterial Communities in Rhizosphere Soil During Growth of Rehmanniae Radix
Weifeng LI ; Xiaotong GENG ; Haiyan GONG ; Fengqing WANG ; Jingwei LEI ; Caixia XIE ; Zhongyi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(22):149-158
ObjectiveTo analyze the changes of volatile organic compounds (VOCs) and bacterial community characteristics in rhizosphere soil during the growth of Rehmanniae Radix, as well as the relationship between VOCs and bacterial community structure, so as to lay the foundation for the evaluation of the characteristics of continuous cropping soil and the regulation of continuous cropping soil microorganisms. MethodThe rhizosphere soil during the three main growth periods of Rehmanniae Radix in July, August and October was used as the research object. Gas chromatography-mass spectrometry (GC-MS) was used to determine the relative contents of VOCs in ethyl acetate and dichloromethane parts in rhizosphere soil. The characteristics of rhizosphere bacterial community structure was determined by high-throughput sequencing, SPSS 24, SIMCA 14.1 and other software were used to analyze the differences of VOCs and bacterial community structure in rhizosphere soil of the three periods, and the main VOCs and iconic bacteria that caused the differences were screened, and the correlation between VOCs and bacterial community structure was analyzed. ResultThere were differences in VOCs in different parts of rhizosphere soil during the three growth stages of Rehmanniae Radix. Among them, and the main VOCs that cause differences were dioctyl isophthalate, 2-octyl-1-dodecanol and 2-ethylhexyl p-toluic acid in the ethyl acetate part, and 1,3-benzenedicarboxylic acid, di (2-propylpentyl) phthalate and 2-ethylhexyl p-toluenecarboxylic acid in the dichloromethane part. From the seedling stage to the end of tuber enlargement of Rehmanniae Radix, the relative abundance of dominant bacteria such as Actinobacteria, Firmicutes and Chloroflexi in the rhizosphere soil was gradually decreased, and there were unique bacterial communities in rhizosphere soil of each growth stage. Correlation analysis showed that the VOCs in rhizosphere soil of Rehmanniae Radix had an impact on the rhizosphere bacterial community structure, especially the components of esters and alcohols. ConclusionDuring the growth of Rehmanniae Radix, the characteristics of rhizosphere soil are mainly manifested in the content changes of main VOCs such as esters and alcohols and the gradual decrease of the abundance of the main beneficial bacteria, and the VOCs in rhizosphere soil play a certain role in shaping the structure of bacterial community.
9.Efficacy and safety of roxadustat in the treatment of renal anemia in calciphylaxis dialysis patients
Tian XU ; Hong LIU ; Xiaotong XIE ; Bin WANG ; Xiaoliang ZHANG ; Bicheng LIU
Chinese Journal of Nephrology 2022;38(4):313-319
Objective:To observe the efficacy and safety of roxadustat in the treatment of renal anemia in calciphylaxis dialysis patients who had poor response to recombinant human erythropoietin (rHuEPO).Methods:This study was a prospective cohort study. The dialysis patients who were diagnosed with calciphylaxis and had previous regular use of rHuEPO≥3 months with hemoglobin (Hb) levels<110 g/L in the Department of Nephrology of Zhong Da Hospital affiliated to Southeast University from January 1, 2019 to March 28, 2021 were recruited. The effect of oral roxadustat in calciphylaxis dialysis patients with renal anemia was analyzed by self-comparison method.Results:There were totally 18 calciphylaxis dialysis patients with renal anemia enrolled in the study and the age was (49.7±16.2) years old, including 11 males and 7 females, and 14 cases on hemodialysis and 4 cases on peritoneal dialysis. The high-sensitivity C-reactive protein level was 27.3(15.6, 48.5) mg/L(reference value 0-3 mg/L) at baseline. The baseline Hb level was (85.4±11.6) g/L, and after 3 months of oral roxadustat, the Hb level was (105.8±15.2) g/L ( t=-9.282, P<0.001). The Hb compliance rate was 44.4%(8/18). Ferritin decreased significantly at 3 months compared with the baseline level [208.0(59.0, 306.3) μg/L vs 229.0(127.3, 385.2) μg/L, Z=-3.637, P<0.001]. The total iron binding capacity level increased significantly compared with the baseline level [127.0(65.0, 211.5) μmol/L vs 105.5(43.8, 153.7) μmol/L, Z=-2.156, P=0.031]. Transferrin saturation level at 3 months was lower than that at baseline, but there was no significant difference [20.2%(14.2%, 27.7%) vs 20.5%(18.7%, 34.9%), Z=-1.546, P=0.122]. No adverse reactions occurred during the observation period. Conclusion:The application of roxadustat can effectively correct Hb level and improve iron metabolism with high safety in calciphylaxis dialysis patients with renal anemia under inflammatory status.
10.Erratum: Author correction to "A nanocleaner specifically penetrates the blood‒brain barrier at lesions to clean toxic proteins and regulate inflammation in Alzheimer's disease" Acta Pharmaceutica Sinica B 12, (2021) 4032-4044.
Ting LEI ; Zhihang YANG ; Xue XIA ; Yuxiu CHEN ; Xiaotong YANG ; Rou XIE ; Fan TONG ; Xiaolin WANG ; Huile GAO
Acta Pharmaceutica Sinica B 2022;12(6):2965-2967
[This corrects the article DOI: 10.1016/j.apsb.2021.04.022.].

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