Objective To optimize the platelet enrichment method,and to analyze the concentration changes of key molecules in platelet-rich plasma(PRP)before and after activation,as well as the impact of its activated products on the proliferation of rat endothelial progenitor cells.Methods The tube double-centrifu-gation method was employed to optimize platelet enrichment,and the platelet count in the enriched PRP was measured.ELISA was used to detect the concentration changes of vascular endothelial growth factor(VEGF),endostatin(ES),and P-selectin(CD62P)in PRP before and after activation.The PRP was activated by using liquid nitrogen freeze-thaw method,and the effect of its activated products on the proliferation of rat endothelial progenitor cells was evaluated by using the methyl thiazolyl tetrazolium(MTT)assay.Results The optimal enrichment coefficient of platelets achieved by the double-centrifugation method was 4.63.After low-speed,long-duration double centrifugation,the platelet count was highest in the upper layer of the buffy coat.For PRP with a platelet count of 500× 109/L obtained by machine collection,the VEGF con-centrations before and after activation were(3 418.12±488.80)pg/mL and(4 530.04±308.30)pg/mL,re-spectively,the ES concentrations were(6 168.98±253.22)pg/mL and(6 594.65±82.47)pg/mL,respec-tively,the CD62P concentrations were(6 678.23±324.15)pg/mL and(17 630.53±746.24)pg/mL,respec-tively,statistically significant differences were observed in the above indicators before and after activation(P＜0.01).The activated PRP was diluted in a gradient manner by using a specialized culture medium for en-dothelial progenitor cells.MTT assay results indicated that,in the basal medium,the optimal volume fraction for promoting endothelial progenitor cell proliferation was 0.25％after 48 hours of culture;in the complete medium,the optimal volume fractions for promoting endothelial progenitor cell proliferation were 0.062 5％after 24 hours and 0.125％after 48 hours.Conclusion The concentrations of VEGF,ES,and CD62P in the optimized,enriched PRP exhibited significant changes before and after activation.The optimal volume fraction for promoting endothelial progenitor cell proliferation in the basal medium was 0.25％.

Pain management is an important component of military medical support during wartime.Early pain management for wounded soldiers can effectively alleviate pain,which is critical to maintaining combat effectiveness,promoting physiological and psychological recovery of wounded soldiers,preventing chronic pain,and helping them return to the battle field.In recent years,the U.S.Armed Forces have increasingly emphasized prehospital pain management.They have been updating the relevant pain management guidelines to establish a practical system in order to ensure that the pain of wounded soldiers is effectively controlled.This paper reviews the current research on prehospital pain management in the U.S.Armed Forces and summarizes the advanced and practical technologies for prehospital pain management.It provides references for research on prehospital pain management,and optimization of prehospital pain management strate-gies suited to China's operational context,and for the design of related training programs.

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.

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.

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.

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.

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.

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.

OBJECTIVE To evaluate the quality of different germplasms of Rehmannia glutinosa based on iridoid glycosides. METHODS The contents of total iridoid glycosides ，catalpol，rehmaionoside D ，rehmaionoside A ，and leonuride in 18 batches of R. glutinosa from 6 germplasms（85-5，JinJiu，BX，BJ-1，Shandong，QH-1）were determined by ultraviolet spectrophotometry and high performance liquid chromatography. After normalization of the above content determination results ，the quality of different germplasm of R. glutinosa were evaluated by multiple statistical methods such as cluster analysis ，factor comprehensive analysis and partial least squares discriminant analysis （PLS-DA）. RESULTS Among 6 germplasms of R. glutinosa ，the content of total iridoid glycosides in R. glutinosa 85-5 was the highest ，and the content of catalpol in R. glutinosa BX was the highest ；the contents of rehmannioside D and rehmannioside A in R. glutinosa JinJiu were the highest ，and the content of leonuride in R. glutinosa BX was the highest. Cluster analysis showed that R. glutinosa JinJiu were clustered into one category ，R. glutinosa BX clustered into one category ，R. glutinosa Shandong and R. glutinosa BJ-1 were clustered into one category ，and R. glutinosa QH-1 and 85-5 were clustered into one category. Through factor comprehensive analysis ，there were differences in the quality of different germplasms of R. glutinosa . The comprehensive score of R. glutinosa BX，Shandong，85-5，BJ-1，QH-1，JinJiu were 2.283 9，1.689 1，1.664 8， 1.503 3，1.469 0，1.214 6，respectively. PLS-DA showed that variable importance projection value of total iridoid glycosides ， catalpol and leonuride were all higher than 1. CONCLUSIONS The quality difference of R. glutinosa from different germplasms may be caused by total iridoid glycosides ，catalpol and leonuride.

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.