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％.

Objective To evaluate the accuracy and reproducibility of AlignRT-guided positioning by comparing two positioning workflows for pelvic tumor radiotherapy,and to further explore the feasibility of using it to replace skin marker alignment.Methods Forty cases of pelvic tumor treated with radiotherapy using Infinity accelerator in Sun Yat-sen University Cancer Center between March 2022 and March 2023 were included in the study,with 20 cases using the skin marker alignment workflow and the other 20 adopting AlignRT-guided positioning workflow.The translational errors(LAT,LNG,VRT)and rotational errors(Yaw,Pitch,Roll)were determined by the registration of pre-treatment cone-beam CT(CBCT)with planned CT.Both CBCT shifts and error offset distributions were analyzed;planning target volume(PTV)margins were calculated;and correlation analyses were conducted among six-dimensional errors,and between body mass index and setup errors.Results The median translational and rotational setup errors of skin marker alignment workflow vs AlignRT-guided positioning workflow were 0.19-0.34 cm vs 0.10-0.15 cm and 0.50°-1.30°vs 0.50°-0.70°,with the maximum offset ranges of 1.20-1.70 cm vs 0.42-0.47 cm and 2.00°-5.50° vs 1.80°-2.00°,respectively.Additionally,for skin marker alignment workflow,inter-fractional errors>0.5 cm and>3° were observed in 23.3%and 9.8%of fractions.The PTV margins of AlignRT-guided positioning workflow were 0.37,0.38 and 0.34 cm in the left-right,superior-inferior and anterior-posterior directions,respectively,which were much smaller than those of skin marker alignment workflow(0.67,1.22 and 0.95 cm).No correlation was found between six-dimensional errors in two positioning workflows.When using AlignRT-guided positioning workflow,the setup errors in LAT,LNG and Pitch directions had low correlations with body mass index.Conclusion In pelvic tumor radiotherapy,AlignRT-guided positioning can reduce translational and rotational errors,achieve precise setup and excellent inter-fractional reproducibility and stability,and replace traditional skin marker alignment while being used in conjunction with CBCT.

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.

Objective:To evaluate the prevalence, potential risk factors, and correlation between coronary and peripheral microvascular dysfunction in heart failure with non-reduced ejection fraction (nHFrEF) patients.Methods:This was a prospective registry study. nHFrEF patients admitted to Zhongshan Hospital affiliated with Fudan University from December 2021 to December 2023 were enrolled. According to coronary flow reserve (CFR) or reactive congestion index (RHI), enrolled patients were divided into coronary microvascular endothelial dysfunction (CMD) group (CFR<2.5) and no CMD group (CFR≥2.5) or peripheral microvascular endothelial dysfunction (MED) group (RHI<1.67) and no MED group (RHI≥1.67). Patients′ general information, laboratory and auxiliary examination data were collected. Univariate and multivariate logistic regression were used to analyze the influencing factors of CMD and MED in nHFrEF patients, and Spearman correlation analysis was used to evaluate the correlation between MED and CMD.Results:A total of 142 nHFrEF patients were enrolled, aged 69.0 (59.0, 74.0) years, with a male proportion of 66.9% (95/142). The grouping results were as follows: (1) According to CFR, there were 73 cases in the CMD group and 69 cases in the no CMD group; (2) According to RHI, there were 57 cases in the MED group and 85 cases in the no MED group. The prevalence of CMD and MED in this study was 51.4% (73/142) and 40.1% (57/142), respectively. Univariate logistic regression analysis showed that increased heart rate, chronic kidney disease, atrial fibrillation, elevated N-terminal pro-B type natriuretic peptide levels, and increased urinary albumin/creatinine ratio were risk factors for CMD, while increased RHI was a protective factor for CMD; Atrial fibrillation is a risk factor for MED, while increased CFR is a protective factor for MED. Incorporating clinically significant variables from univariate analysis into multivariate analysis, the results showed that increased heart rate and elevated RHI remained risk and protective factors for CMD, respectively; increased CFR remains a protective factor for MED. Spearman correlation analysis showed that CFR was negatively correlated with lg urinary albumin/creatinine ratio, lg cardiac troponin T, lg N-terminal pro-B type natriuretic peptide, and heart rate; RHI is positively correlated with CFR.Conclusions:The prevalence of CMD and MED in nHFrEF patients is high, and the two have a certain positive correlation. Increased heart rate and RHI are risk and protective factors for CMD, respectively, while increased CFR is a protective factor for MED. MED may be a potential therapeutic target for nHFrEF patients.

Objective:To evaluate the correlation between preoperative platelet function and in-hospital mortality in patients with acute Stanford A aortic dissection(ATAAD) undergoing emergency surgery.Methods:ATAAD emergency surgical patients who underwent preoperative thromboelastography(TEG) examination at three cardiovascular disease hospitals from January 2018 to December 2023 were consecutively selected in this study. The patients were divided into two groups according to whether the patient survived to discharge.Results:867 patients were included in this study. The in-hospital mortality was 11.2%(97 cases). Compared with the DG group(97 cases), the age, pericardial effusion volume, lactate concentration, and MA value of patients in the SG group(770 cases) were higher( P<0.001). Factors independently associated with in-hospital mortality were age(>60 years old), coronary hypoperfusion, pericardial effusion volume(>200.00 ml), and MA value(<60.6 mm). There was a correlation between MA value and in-hospital mortality( P=0.012), and the mediating effect between MA value and platelet count was not significant. Conclusion:There is a correlation between preoperative platelet function and in-hospital in ATAAD patients, and improving platelet function may be one of the important ways to improve the clinical prognosis of those patients.

Objective To evaluate the accuracy and reproducibility of AlignRT-guided positioning by comparing two positioning workflows for pelvic tumor radiotherapy,and to further explore the feasibility of using it to replace skin marker alignment.Methods Forty cases of pelvic tumor treated with radiotherapy using Infinity accelerator in Sun Yat-sen University Cancer Center between March 2022 and March 2023 were included in the study,with 20 cases using the skin marker alignment workflow and the other 20 adopting AlignRT-guided positioning workflow.The translational errors(LAT,LNG,VRT)and rotational errors(Yaw,Pitch,Roll)were determined by the registration of pre-treatment cone-beam CT(CBCT)with planned CT.Both CBCT shifts and error offset distributions were analyzed;planning target volume(PTV)margins were calculated;and correlation analyses were conducted among six-dimensional errors,and between body mass index and setup errors.Results The median translational and rotational setup errors of skin marker alignment workflow vs AlignRT-guided positioning workflow were 0.19-0.34 cm vs 0.10-0.15 cm and 0.50°-1.30°vs 0.50°-0.70°,with the maximum offset ranges of 1.20-1.70 cm vs 0.42-0.47 cm and 2.00°-5.50° vs 1.80°-2.00°,respectively.Additionally,for skin marker alignment workflow,inter-fractional errors>0.5 cm and>3° were observed in 23.3%and 9.8%of fractions.The PTV margins of AlignRT-guided positioning workflow were 0.37,0.38 and 0.34 cm in the left-right,superior-inferior and anterior-posterior directions,respectively,which were much smaller than those of skin marker alignment workflow(0.67,1.22 and 0.95 cm).No correlation was found between six-dimensional errors in two positioning workflows.When using AlignRT-guided positioning workflow,the setup errors in LAT,LNG and Pitch directions had low correlations with body mass index.Conclusion In pelvic tumor radiotherapy,AlignRT-guided positioning can reduce translational and rotational errors,achieve precise setup and excellent inter-fractional reproducibility and stability,and replace traditional skin marker alignment while being used in conjunction with CBCT.

Objective:To evaluate the correlation between preoperative platelet function and in-hospital mortality in patients with acute Stanford A aortic dissection(ATAAD) undergoing emergency surgery.Methods:ATAAD emergency surgical patients who underwent preoperative thromboelastography(TEG) examination at three cardiovascular disease hospitals from January 2018 to December 2023 were consecutively selected in this study. The patients were divided into two groups according to whether the patient survived to discharge.Results:867 patients were included in this study. The in-hospital mortality was 11.2%(97 cases). Compared with the DG group(97 cases), the age, pericardial effusion volume, lactate concentration, and MA value of patients in the SG group(770 cases) were higher( P<0.001). Factors independently associated with in-hospital mortality were age(>60 years old), coronary hypoperfusion, pericardial effusion volume(>200.00 ml), and MA value(<60.6 mm). There was a correlation between MA value and in-hospital mortality( P=0.012), and the mediating effect between MA value and platelet count was not significant. Conclusion:There is a correlation between preoperative platelet function and in-hospital in ATAAD patients, and improving platelet function may be one of the important ways to improve the clinical prognosis of those patients.

Objective:To evaluate the prevalence, potential risk factors, and correlation between coronary and peripheral microvascular dysfunction in heart failure with non-reduced ejection fraction (nHFrEF) patients.Methods:This was a prospective registry study. nHFrEF patients admitted to Zhongshan Hospital affiliated with Fudan University from December 2021 to December 2023 were enrolled. According to coronary flow reserve (CFR) or reactive congestion index (RHI), enrolled patients were divided into coronary microvascular endothelial dysfunction (CMD) group (CFR<2.5) and no CMD group (CFR≥2.5) or peripheral microvascular endothelial dysfunction (MED) group (RHI<1.67) and no MED group (RHI≥1.67). Patients′ general information, laboratory and auxiliary examination data were collected. Univariate and multivariate logistic regression were used to analyze the influencing factors of CMD and MED in nHFrEF patients, and Spearman correlation analysis was used to evaluate the correlation between MED and CMD.Results:A total of 142 nHFrEF patients were enrolled, aged 69.0 (59.0, 74.0) years, with a male proportion of 66.9% (95/142). The grouping results were as follows: (1) According to CFR, there were 73 cases in the CMD group and 69 cases in the no CMD group; (2) According to RHI, there were 57 cases in the MED group and 85 cases in the no MED group. The prevalence of CMD and MED in this study was 51.4% (73/142) and 40.1% (57/142), respectively. Univariate logistic regression analysis showed that increased heart rate, chronic kidney disease, atrial fibrillation, elevated N-terminal pro-B type natriuretic peptide levels, and increased urinary albumin/creatinine ratio were risk factors for CMD, while increased RHI was a protective factor for CMD; Atrial fibrillation is a risk factor for MED, while increased CFR is a protective factor for MED. Incorporating clinically significant variables from univariate analysis into multivariate analysis, the results showed that increased heart rate and elevated RHI remained risk and protective factors for CMD, respectively; increased CFR remains a protective factor for MED. Spearman correlation analysis showed that CFR was negatively correlated with lg urinary albumin/creatinine ratio, lg cardiac troponin T, lg N-terminal pro-B type natriuretic peptide, and heart rate; RHI is positively correlated with CFR.Conclusions:The prevalence of CMD and MED in nHFrEF patients is high, and the two have a certain positive correlation. Increased heart rate and RHI are risk and protective factors for CMD, respectively, while increased CFR is a protective factor for MED. MED may be a potential therapeutic target for nHFrEF patients.

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.

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.