OBJECTIVE To investigate and analyze the current management of drug clinical trial institutions in Jiangxi Province and the situation of undertaking drug clinical trials after the implementation of the filing system. METHODS A survey was conducted on 38 new institutions （obtained qualifications during the implementation of the filing system） and old institutions （obtained qualifications during the implementation of the recognition system） that had completed drug clinical trial institution qualification filing for more than one year in Jiangxi Province. The survey focused on the basic information of the institutions， the number of registered principal investigator （PI）， institutional hardware and information construction， personnel allocation and training， and drug registration clinical trials undertaken by the institutions. RESULTS Of 38 institutions surveyed， there were 22 general hospitals and 16 specialized hospitals； there were 24 old institutions and 14 new institutions. Whether in general hospitals or specialized hospitals， the old institutions were better than the new institutions in the number of approved beds， the number of outpatients， the number of inpatients， the number of specialties， and the number of PI； both old and new institutions had separate offices； all new institutions were set up with GCP pharmacy. The adoption of clinical trial management system in new institutions is significantly less than in old institutions. In the general hospital， both the number of full-time managers and the number of quality controllers in old institutions were significantly more than in the new institutions， while the opposite was true at the level of specialized hospitals. In terms of centralized training on GCP， new institutions were all better than the old ones. Whether in general hospitals or specialized hospitals， the number of drug registration clinical trial projects undertaken by new institutions was significantly less than that of old ones. CONCLUSIONS The new institutions are worse than the old institutions in comprehensive strength and information construction of hospitals， and the number of clinical trials undertaken by new institutions is also less than old institutions.

[Objective] To establish a cryopreservation protocol for small-volume (≤1 mL) red blood cells (RBCs) and to evaluate the reactivity and stability of blood group antigens after cryopreservation, so as to explore its potential application in immunohematology reference laboratories. [Methods] Small-volume RBCs were cryopreserved for 120 days, followed by thawing and deglycerolization to restore the RBC components. The quality of the RBCs was assessed. Serum antibodies were serially diluted and reacted with RBCs before and after cryopreservation, and agglutination scores were recorded to quantitatively evaluate the reactivity and stability of blood group antigens such as Rh, Duffy, Lewis, Kidd, M, and H. Flow cytometry was used to analyze the percentage and mean fluorescence intensity of ABO antigen expression on RBCs before and after cryopreservation to assess the usability of cryopreserved RBCs in flow immunophenotyping and blood group subtype studies. [Results] The hemolysis rate of thawed and deglycerolized RBCs was (0.27±0.10)%, with a supernatant free hemoglobin level of (0.52±0.14) g/L, and the RBC recovery rate was (69.12±7.91)%. The direct antiglobulin test (DAT) was negative for all thawed RBCs. There was no difference in the reactivity of blood group antigens before and after cryopreservation, and no difference in the percentage and mean fluorescence intensity of A and B antigen expression on RBCs before and after cryopreservation. [Conclusion] The small-volume RBC cryopreservation protocol can be applied to immunohematology analysis in reference laboratories and is expected to be widely used in blood group identification, antibody screening, identification, and blood group-related research.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

OBJECTIVE To summarize the current status of position training for clinical pharmacists in China and provide references for the continuous optimization of such training programs. METHODS SinoMed， CNKI，VIP and Wanfang Data were electronically searched to collect position training of clinical pharmacists studies from the inception until November 5th 2024. After data extraction and quality evaluation， descriptive analysis was performed on the results of the included studies. RESULTS & A total of 68 pieces of relevant literature were included in the study. Among them， 50 studies reported on training content， 49 involved the allocation of teaching resources in the bases， 48 addressed training methods， and 39 focused on training evaluation； only 2 studies mentioned faculty development. There were notable variations in the clinical pharmacist training programs across different bases， particularly in the allocation of teaching resources， such as the composition of the teaching team and the utilization of auxiliary teaching tools. Additionally， differences existed in training approaches， such as those employing a single method versus a blended approach. Conversely， the core training content of each base generally revolved around clinical pharmacy practice， demonstrating a degree of consistency. Moreover， the overall emphasis on teacher training and assessment tended to be obviously insufficient. Each base can focus on enhancing the competence of clinical pharmacists by allocating teaching resources， selecting training methods， improving training content， and using evaluation tools， to further enhance the quality of clinical pharmacist training.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

OBJECTIVE: To investigate correlation between preoperative C ₂ slope (C2S) and effectiveness at 2 years after short-segment anterior cervical discectomy and fusion (ACDF), with the aim of providing reliable indicators for predicting effectiveness. METHODS: One hundred and eighteen patients with cervical spondylotic myelopathy, who received short-segment ACDF between January 2018 and December 2022 and met the selection criteria, were enrolled in the study. There were 46 males and 72 females, aged from 26 to 80 years, with a mean age of 53.6 years. The operative duration was (127.6±33.46) minutes and the intraoperative blood loss was (34.75±30.40) mL. All patients were followed up 2 years. The pre- and post-operative Neck Disability Index (NDI), Japanese Orthopaedic Association (JOA) score, and visual analogue scale (VAS) score for pain were recorded. Based on the anteroposterior and lateral cervical X-ray films, the sagittal parameters of the cervical spine were measured [C ₂-C ₇ Cobb angle, C ₀-C ₂ Cobb angle, T ₁ slope, C2S, sagittal segmental angle (SSA) of the surgical segment, and average surgical disc height (ASDH) of the surgical segment]. Statistical analyses were performed to assess the differences in these indicators between pre- and post-operation, as well as the correlations between the preoperative C2S and the JOA score, NDI, and VAS score at 2 years after operation. The patients were allocated into group A (C2S >11.73°) and group B (C2S≤ 11.73°) according to the median value of the preoperative C2S (11.73°). The JOA score, NDI, and VAS score before operation and at 2 years after operation, as well as the differences between pre- and post-operative values (change values), were compared between the two groups. RESULTS: The T ₁ slope, C ₂-C ₇ Cobb angle, C ₀-C ₂ Cobb angle, SSA, and ASDH at immediate after operation and JOA score, NDI, and VAS score at 2 years after operation significantly improved in 118 patients when compared with preoperative ones ( P<0.05). Pearson correlation analysis showed that preoperative C2S was not correlated with JOA score and NDI at 2 years after operation ( P>0.05), but negatively correlated with VAS score ( P<0.05). There were 59 patients with preoperative C2S>11.73° (group A) and 59 with C2S≤11.73° (group B). There was no significant difference in preoperative JOA score, NDI, and VAS score between the two groups ( P>0.05). There were significant differences in VAS score at 2 year after operation and the change value between the two groups ( P<0.05); there was no significant difference in the JOA score and NDI ( P>0.05). CONCLUSION Patients with cervical spondylotic myelopathy and a higher preoperative C2S exhibited superior long-term pain relief and effectiveness following short-segment ACDF.
Humans ; Male ; Spinal Fusion/methods* ; Female ; Middle Aged ; Cervical Vertebrae/diagnostic imaging* ; Diskectomy/methods* ; Aged ; Adult ; Treatment Outcome ; Aged, 80 and over ; Spondylosis/diagnostic imaging* ; Pain Measurement ; Preoperative Period ; Follow-Up Studies

OBJECTIVE: To investigate the relationship between peripheral blood T-cell immunoglobulin mucin-3 (TIM-3) and iron overload in patients with myelodysplastic syndrome (MDS) undergoing red blood cell transfusion. METHODS: 120 MDS patients who received treatment at Wuhan Third Hospital from June 2020 to May 2022 were included and analyzed as research subjects, all of whom met the indications for red blood cell transfusion. Blood routine and biochemical indicators were tested before transfusion, and general clinical data of the patients were statistically analyzed. The iron metabolism status of the patients were evaluated. The clinical characteristics of patients with iron overload and the factors affecting iron overload were analyzed. And a correlation analysis was conducted between TIM-3 and other factors affecting iron overload. RESULTS: Among the 120 MDS patients included in this study, 82 cases (68.33%) were detected to have iron overload after red blood cell transfusion. The occurrence time of iron overload was 20-42 weeks, with an average time of 32.35±5.26 weeks, calculated from the first transfusion of red blood cells. The proportion of patients with high-risk and extremely high-risk according to the revised International Prognostic Scoring System (IPSS-R) and WHO classification-based Prognostic Scoring System (WPSS), the volume of blood transfusions, the proportion of transfusion-dependent patients, and the levels of serum hepcidin (Hepc), erythropoietin (EPO), and TIM-3 in patients with iron overload were higher than those in patients with normal iron metabolism, and the differences were statistically significant (P < 0.05). Logistic regression analysis showed that high-risk and extremely high-risk according to WPSS, blood transfusion volume, transfusion dependence, and upregulation of serum Hepc, EPO, and TIM-3 expression were factors affecting iron overload in MDS patients undergoing red blood cell transfusion (P < 0.05). Pearson correlation analysis showed that serum TIM-3 level in MDS patients were positively correlated with the other factors affecting iron overload (P < 0.05). CONCLUSION Serum TIM-3 is associated with iron overload in MDS patients undergoing red blood cell transfusion, and upregulation of serum TIM-3 expression increases the risk of iron overload after red blood cell transfusion.
Humans ; Myelodysplastic Syndromes/blood* ; Iron Overload/blood* ; Hepatitis A Virus Cellular Receptor 2/blood* ; Erythrocyte Transfusion ; Male ; Female ; Middle Aged ; Aged ; Iron

Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.

ObjectiveTo investigate the application of the novel inflammatory factor adsorption column CA280 combined with low-dose plasma exchange （LPE） in patients with acute-on-chronic liver failure （ACLF）. MethodsA prospective cohort study was designed， and a total of 93 ACLF patients who were admitted to The Ninth Hospital of Nanchang from June 2023 to January 2025 were enrolled and randomly divided into DPMAS+LPE group with 50 patients and CA280+LPE group with 43 patients. In addition to comprehensive medical treatment， the patients in the DPMAS+LPE group received DPMAS and LPE treatment， and those in the CA280+LPE group received CA280 and LPE treatment. The two groups were observed in terms of routine blood test results， liver function parameters， renal function markers， electrolytes， coagulation function parameters， cytokines， adverse events， and 28-day prognosis before surgery （baseline）， during surgery （DPMAS or CA280）， and after surgery （after sequential LPE treatment）. The paired t-test was used for comparison of normally distributed continuous data before and after treatment within each group， and the independent-samples t test was used for comparison between groups； the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment within each group， and the Mann-Whitney U test was used for comparison between groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups， and the Spearman test was used for correlation analysis. ResultsAfter CA280 treatment， the ACLF patients had significant reductions in the levels of cytokines （IL-6， IL-8， IL-10， TNF-α， and IFN-γ）， liver function parameters （ALT， AST， ALP， TBil， DBil， Alb， and glutathione reductase）， and the renal function marker urea nitrogen （all P<0.05）， and in terms of coagulation function parameters， there were significant increases in prothrombin time， activated partial thromboplastin time （APTT）， thrombin time， and international normalized ratio （INR） and significant reductions in prothrombin activity （PTA） and fibrinogen （FIB） （all P<0.05）. Compared with the DPMAS+LPE group， the CA280+LPE group showed better improvements in the serum cytokines IL-8 （Z=-2.63， P=0.009）， IL-10 （Z=-3.94， P<0.001）， and TNF-α （Z=-1.53， P=0.023）， and the two artificial liver support systems had a similar effect in improving liver function （ALT， AST， GGT， GR， TBil， and DBil） （all P >0.05）， but the CA280+LPE group showed a significantly greater reduction in Alb （Z=-2.08， P=0.037）. CA280+LPE was more effective in reducing uric acid （Z=-2.97， P=0.003）. Compared with DPMAS+LPE， CA280+LPE treatment resulted in a significant reduction in INR （Z=-4.01， P<0.001）， a significant increase in APTT （Z=-2.53， P=0.011）， and significant greater increases in PTA （Z=-6.28， P<0.001） and FIB （Z=-3.93， P<0.001）. There were no significant differences in the incidence rates of adverse reactions and the rate of improvement at discharge between the two groups （all P>0.05）. The Spearman correlation analysis showed that IL-6 was significantly correlated with WBC （r=0.22， P=0.042）， TBil （r=0.29， P=0.005）， and FIB （r=-0.33， P=0.003）； IL-8 was positively correlated with APTT （r=0.37， P<0.001） and INR （r=0.25， P=0.013）； TNF-α was significantly correlated with WBC （r=0.40， P<0.001） and TBil （r=0.34， P<0.001）. ConclusionCompared with DPMAS， CA280 combined with LPE can effectively clear proinflammatory cytokines and improve liver function in ACLF patients， but it has a certain impact on Alb and coagulation function. This regimen provides a new option for the individualized treatment of ACLF and can improve the short-term prognosis of patients， but further studies are needed to verify its long-term efficacy.