Objective: To investigate the protective effects and underlying mechanisms of sodium pyruvate (SP) on RBC storage lesions using an oxidative damage model. Methods: Six units of leukocyte-depleted suspended RBCs (discarded for non-infectious reasons within three days post-collection) were randomly assigned to four groups: negative control (NS), positive control (PS), experimental group 1 (SP1), and experimental group 2 (SP2). Oxidative stress was induced in the PS group by the addition of hydrogen peroxide (H O ), while SP1 and SP2 received SP supplementation at different concentrations (25 mM and 50 mM, respectively) in the presence of H O . After 1 hour of incubation, RBC morphology was assessed microscopically, and biochemical indicators including glutathione (GSH), malondialdehyde (MDA), methemoglobin (MetHb), adenosine triphosphate (ATP), and Na /K -ATPase activity were measured. Results: RBCs in the PS group exhibited pronounced morphological damage, including cell shrinkage and echinocyte formation, whereas both SP-treated groups showed significantly reduced structural injury. SP treatment led to elevated GSH levels and decreased concentrations of MDA and MetHb, suggesting attenuation of oxidative stress. Additionally, SP enhanced intracellular ATP levels and Na /K -ATPase activity, thereby contributing to membrane stability. Notably, the SP2 group (50 mM) demonstrated superior protective effects compared to SP1 (25 mM). Conclusion: Sodium pyruvate effectively attenuates oxidative storage lesions in RBCs, primarily through its antioxidant properties, energy metabolism supporting ability, and celluar membrane stabilizing function. These findings suggest SP as a promising additive for enhancing the quality and safety of stored RBCs.

ObjectiveTo investigate the change and potential role of Mindin protein in the treatment of chronic hepatitis B （CHB） with PEG-IFNα-2b. MethodsA total of 29 CHB patients who received the treatment with PEG-IFNα-2b in The Second Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 were enrolled， and according to their clinical outcome， they were divided into cured group with 17 patients and uncured group with 12 patients. Peripheral blood samples were collected from both groups at baseline， 12 weeks， and 24 weeks to measure blood routine indices， liver function parameters， hepatitis B markers， and Mindin protein. HBsAg， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Mindin protein at different time points were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； a Spearman correlation analysis was used to investigate correlation； a multiple linear regression analysis was used to investigate the influence of HBsAg and ALT on the content of Mindin protein. ResultsThe analysis of baseline data showed that there were significant differences in the levels of HBsAg， HBeAb， albumin， and albumin/globulin ratio between the cured group and the uncured group （all P<0.05）. The cured group tended to have a gradual increase in the level of Mindin， and the level of Mindin at 24 weeks was significantly higher than that at baseline （P<0.05）. The cured group had a significantly higher level of Mindin protein than the uncured group at 24 weeks （P=0.019）. The cured group had a significantly lower level of HBsAg than the uncured group （P<0.05）， with a significant change from baseline to each time point within the cured group （P<0.05）. In addition， the levels of ALT and AST in the cured group tended to first increase and then decrease， and the expression levels at 12 weeks were significantly higher than those at baseline （P<0.05）. At 12 weeks， there was a strong linear correlation between Mindin protein levels and ALT in the untreated group （r=0.760 8， P<0.05）， and further multiple linear regression analysis also demonstrated a linear relationship between the two （b=1.571， P=0.019）. ConclusionThere is a significant difference in the level of Mindin protein between the cured group and the non-cured group after 24 weeks of PEG-IFNα-2b antiviral treatment， and therefore， detecting the dynamic changes of Mindin protein can better predict the treatment outcome of CHB， which provides a reference for clinical practice.

Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90％confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00％-125.00％.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.

Objective To compare the efficacy of trastuzumab plus pertuzumab(HP)combined with either nab-paclitaxel plus carboplatin or docetaxel plus carboplatin as neoadjuvant therapy for HER2-positive breast cancer in real-world clinical practice.Methods Clinical data of HER2-positive breast cancer patients who received neoadjuvant therapy with either HP combined with nab-paclitaxel plus carboplatin or HP combined with docetaxel plus carboplatin and subsequently underwent surgery were retrospectively collected from 11 tertiary grade-A hospitals in Hebei Province from June 2019 to December 2021.The total pathological complete response(tpCR)rates of the two groups were compared.Results A total of 76 patients were included in the study,with 47 in the nab-paclitaxel group and 29 in the docetaxel group.The tpCR rate was significantly higher in the nab-paclitaxel group than that in the docetaxel group(72.3%vs.48.3%,χ2=4.463,P=0.035).Subgroup analysis indicated that patients older than 40 years,with cN2-3,cTNM stage Ⅲ,hormone receptor-positive status,and Ki67>30%had significantly higher tpCR rates in the nab-paclitaxel group than those in the docetaxel group(P<0.05).Conclusion In real-world clinical practice,the efficacy of HP combined with nab-paclitaxel plus carboplatin as neoadjuvant therapy for HER2-positive breast cancer is superior to that of HP combined with docetaxel plus carboplatin.

Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.

Objective:To analyze the prognostic outcomes of 1 147 patients who underwent liver transplantation at Qingdao University Affiliated Hospital and to summarize measures to enhance the efficacy of liver transplantation.Methods:A retrospective analysis was conducted on the clinical and follow-up data of 1 147 liver transplant patients at Qingdao University Affiliated Hospital.Results:The overall postoperative 1-, 3-, and 5-year survival rates for the 1 147 liver transplant patients were 87.20%, 73.40%, and 65.60%, respectively. The survival rates for benign disease liver transplant recipients were 88.01%, 84.98%, and 81.39% at 1, 3, and 5 years post-transplant, respectively, compared to recipients transplanted for malignancies of 78.11%, 64.41%, and 60.06% (all P<0.001). Among the mid vs more recent period, patients' 1-year and 3-year postoperative survival rates were 84.20%, 70.80% vs 90.50%, 71.70%, respectively,significantly in favor of recently enrolled patients ( P=0.022). In the complex surgery group, patients' 1-, 3-, and 5-year survival rates were 82.70%, 65.50%, 56.70%, while in less complicated group, it was 89.00%, 76.50%, 69.20% ( P<0.001). The primary causes of death for benign disease recipients were multi-organ failure (4.1%), while in recipients with malignant disease primary cause of death was tumor recurrence (23.7%). Postoperative complications included primary graft dysfunction, delayed graft function recovery, portal vein thrombosis, hepatic artery thrombosis, biliary stricture, post-transplant lymphoproliferative disorder, and graft-versus-host disease, with occurrence rates of 1.05%, 6.89%, 1.92%, 0.44%, 2.00%, 0.61%, and 0.44%, respectively. Conclusions:With the continuous improvement in surgical techniques and perioperative care levels, the 3-year survival rate of recipients at our center has increased. Malignant diseases and complex liver transplantation remain crucial factors affecting recipient prognosis, highlighting the need to further enhance comprehensive treatment capabilities for patients with malignant diseases and complex surgeries.

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.
Rats ; Mice ; Animals ; Rats, Sprague-Dawley ; Angiotensin II/pharmacology* ; Fibroblasts ; Mice, Inbred C57BL ; Fibrosis ; Collagen/pharmacology* ; Collagen Type I/metabolism* ; RNA, Messenger/metabolism* ; Myocardium/pathology*

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*

Objective:To investigate the clinical application value of left ventricular myocardial strain obtained by cardiac MR (CMR) in recent major adverse cardiovascular events (MACE) in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).Methods:From January 2020 to December 2020, a total of 163 patients successfully underwent primary PCI and underwent CMR examination within one week after surgery at Affiliated Hospital of Xuzhou Medical University. The scan sequences included rapid balance-fast field echo and late-gadolinium enhancement. CVI42 post-processing software was used to analyze and measure the left ventricular myocardial strain indices, including left ventricular global longitudinal strain (GLS), left ventricular global circumferential strain (GCS), and left ventricular global radial strain (GRS). According to the results of the 1-year follow-up after surgery, the patients were divided into the MACE group ( n=28) and the non-MACE group ( n=135). For continuous variables with a normal distribution, the t test of two independent samples was used for comparisons between groups. For continuous variables with an abnormal distribution, the variables were compared and analyzed by the rank sum test. For categorical variables, the χ 2 tests were used for between-group comparisons. Cox regression was used to analyze the prognostic value of myocardial strain on the development of MACE in patients with STEMI. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of myocardial strain parameters, and the optimal cut-off value was evaluated by calculating the Youden index. Results:The GLS, GCS, and GRS of the MACE group were (-10.4±3.3)%, [-11.9 (-14.5, -9.3)]%, and (18.3±6.3)%, respectively, and those of the non-MACE group were (-13.7±3.4)%, [-14.6 (-16.4, -11.7)]%, and (22.3±6.1)%, respectively. The difference between the two groups was statistically significant ( t/ Z=-4.71, -3.04, 3.21, P<0.05). Multivariate Cox regression analysis showed that GLS was an independent predictor of MACE (HR=1.546, 95%CI 1.180-2.027, P=0.002). The ROC curve analysis showed that GLS had the largest area under the curve (AUC) (AUC=0.754, 95%CI 0.658-0.851, P<0.001), with a cut-off value of -12.45%. Its diagnostic sensitivity was 71.4%, and the specificity was 67.4%. The value was better than that of the traditional predictor of STEMI prognosis, namely, left ventricular ejection fraction (AUC=0.680, 95%CI 0.567-0.793, P=0.003). Conclusion:GLS of CMR is an independent predictor of MACE in STEMI patients undergoing primary PCI.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.