Objective: To explore the distribution characteristics and influencing factors of adverse reactions in whole blood donation in Jinan, Shandong, so as to provide evidence for the prevention and control of such adverse reactions in this region. Methods: A retrospective analysis was conducted on whole blood donors and adverse reaction cases in Jinan during 2023. To explore influencing factors of adverse reactions, univariate and multivariate logistic regression analyses were used to examine the relationships between adverse reactions and factors such as gender, age, donation organization mode, donation frequency, donation volume, time slot, and health examination results. Results: A total of 122 961 whole blood donations were recorded in Jinan in 2023. Donation-related adverse reactions occurred in 2 054 cases, with an incidence rate of 1.67%. Univariate analysis revealed significant differences in the incidence of adverse reactions across donor characteristics: the rate was higher in females (2.35%, 921/39 192) than in males (1.35%, 1 133/83 769), donors aged 18-25 years had the highest incidence (3.48%, 1 799/51 733), the incidence in group donations (3.13%, 1,737/55 534) was significantly higher than in individual donations (0.47%, 317/67 427), and insufficient blood collection was closely associated with adverse reactions (all P<0.001). Multivariate logistic regression analysis identified group donation, female gender, and a pulse rate of 81-99 beats per minute as risk factors for adverse reactions (all P<0.001), while systolic blood pressure of 116-139 mmHg and diastolic blood pressure of 76-89 mmHg were protective factors (all P<0.05). Compared to younger and lower-weight donor groups, older and higher-weight donors had a significantly lower risk of adverse reactions (all P<0.05). Donors giving 400 mL had a higher risk than those giving 200 mL (P<0.001). In addition, compared with the donation time slot of 7:00-8:59, the risk of adverse reactions was significantly higher during 9:00-16:59, with the time slot of 13:00-14:59 showing the most prominent risk (all P<0.05). However, no statistically significant difference was observed between the time slot of 17:00-20:59 and that of 7:00-8:59 (P>0.05). The primary clinical manifestation of adverse reactions was donation-related vasovagal reaction, with mental tension being the leading precipitating factor, accounting for 69.08% (1 419/2 054) of cases. Conclusion: The occurrence of adverse reactions in whole blood donation in the Jinan is influenced by multiple factors, including donor demographic characteristics, donation organization mode, physiological indicators, and time of donation. It is recommended to enhance the identification and intervention for high-risk groups, and optimize donation processes and service models to reduce the incidence of adverse reactions, thereby ensuring donor safety and blood quality.

Human lactate dehydrogenase A (LDHA) is an NADH-dependent oxidoreductase that catalyzes the conversion of pyruvate to lactate, playing a crucial role in the aerobic glycolysis of tumor cells. Additionally, LDHA is responsible for catalyzing the conversion of glyoxylate to oxalate in the liver, excessive accumulation of which leads to hyperoxaluria. Representative LDHA inhibitors reported to date include GNE-140, NCATS-SM1441, and CHK-336. In this study, NCATS-SM1441 was used as the lead compound. Based on the analysis of its cocrystal binding mode with LDH, the key carboxythiazole and aromatic pharmacophores were retained, while the original substituted pyrazole linker was replaced with urea linker moieties to simplify the structure. As a result, nine urea derivatives were designed and synthesized. Subsequently, on the basis of structure-activity relationship and molecular docking studies, nine target triazole compounds were further designed. Ultimately, triazole compound 25 was found to exhibit the most potent LDHA inhibitory activity (IC50 = 1.59 μmol/L) in vitro. Molecular dynamics simulations were employed to analyze the interactions between compound 25 and key amino acid residues. Finally, the prediction of physicochemical properties and the evaluation of cell viability were performed for compound 25. The study provides an experimental basis for future development of novel LDHA inhibitors with improved drugability.

ObjectiveThe Golgi apparatus serves as a central hub in the eukaryotic secretory pathway, responsible for the processing, sorting, and trafficking of proteins and lipids. In mammalian cells, the Golgi typically forms a perinuclear ribbon-like structure composed of laterally connected cisternae stacks.The maintenance of Golgi ribbon structure depends on the balance of membrane flux across multiple intracellular trafficking pathways, yet the specific contributions of distinct trafficking branches to Golgi macroscopic morphology remain elusive. In mammalian cells, the Golgi ribbon is typically organized as a perinuclear, laterally connected structure composed of stacked cisternae, and its integrity is highly dynamic and sensitive to perturbations in membrane trafficking. This study aims to elucidate the role of coat protein complex I (COPI)-mediated retrograde transport in maintaining the Golgi ribbon and to dissect the functional relationship between the transmembrane cargo receptors LEPROT/LEPROTL1 (LEPROTs) and the COPI adaptor GOLPH3. MethodsUsing siRNA interference and gene-deficient cell lines, we selectively perturbed COPI- or adaptor protein complex 1 (AP-1)-mediated trafficking pathways in HeLa cells. To quantitatively evaluate Golgi morphology, we employed a “Golgi Angle”-based measurement to assess its circumferential distribution around the nucleus. The spatial distribution of the Golgi ribbon was quantitatively analyzed using confocal microscopy, while Golgi ultrastructure and vesicle density were examined via transmission electron microscopy. Additionally, the subcellular distribution of COPI components was assessed by immunofluorescence co-localization. ResultsSelective inhibition of COPI retrograde transport significantly induced the circumferential extension of the Golgi ribbon around the nucleus, whereas blocking AP-1-mediated anterograde transport resulted in Golgi compaction, indicating opposing roles. These results suggest that different trafficking branches downstream of ARF1 exert distinct and even antagonistic effects on Golgi morphology. LEPROTs-deficient cells exhibited a Golgi extension phenotype highly consistent with COPI impairment. Furthermore, knockdown of GOLPH3 in a LEPROTs double-knockout background produced a significant additive effect on Golgi extension, suggesting that LEPROTs and GOLPH3 play non-redundant roles in regulating COPI-related trafficking processes. Mechanistically, loss of either LEPROTs or GOLPH3 led to the aberrant accumulation of COPI components at endoplasmic reticulum exit sites, accompanied by a reduction in COPI-like vesicles around the Golgi. This redistribution indicates a defect in COPI recycling between the ER-Golgi interface and the Golgi apparatus. Ultrastructural analysis revealed that Golgi cisternae in defective cells became shorter and thicker while maintaining a stable number of stacks. In parallel, the density of Golgi-associated vesicles was markedly decreased, further supporting an impairment in COPI vesicle formation or budding processes. ConclusionThis study demonstrates that active COPI retrograde transport is a critical factor in restricting the over-connection of the Golgi ribbon and maintaining its compactness. Rather than causing fragmentation, partial disruption of COPI function leads to a distinct morphological outcome characterized by Golgi ribbon extension at the light microscopy level and cisternal remodeling at the ultrastructural level. LEPROTs and GOLPH3 cooperatively promote the recycling and vesiculation of COPI components, thereby imposing a structural constraint on the Golgi periphery. Our findings support a model in which multiple adaptor proteins act in parallel to sustain efficient COPI cycling, thereby maintaining Golgi structural homeostasis. These findings provide new cell biological evidence for the membrane trafficking basis of Golgi morphological homeostasis.

BACKGROUND:Neuregulin 1 has been shown to be characterized in cell proliferation,differentiation,and vascular growth.Human amniotic mesenchymal stem cells are important seed cells in the field of tissue engineering,and have been shown to be involved in tissue repair and regeneration. OBJECTIVE:To construct human amniotic mesenchymal stem cells overexpressing neuregulin 1 and investigate their proliferation and migration abilities,as well as their effects on wound healing. METHODS:(1)Human amniotic mesenchymal stem cells were in vitro isolated and cultured and identified.(2)A lentivirus overexpressing neuregulin 1 was constructed.Human amniotic mesenchymal stem cells were divided into empty group,neuregulin 1 group,and control group,and transfected with empty lentivirus and lentivirus overexpressing neuregulin 1,or not transfected,respectively.(3)Edu assay was used to detect the proliferation ability of the cells of each group,and Transwell assay was used to detect the migration ability of the cells.(4)The C57 BL/6 mouse trauma models were constructed and randomly divided into control group,empty group,neuregulin 1 group,with 8 mice in each group.Human amniotic mesenchymal stem cells transfected with empty lentivirus or lentivirus overexpressing neuregulin-1 were uniformly injected with 1 mL at multiple local wound sites.The control group was injected with an equal amount of saline.(5)The healing of the trauma was observed at 1,7,and 14 days after model establishment.Histological changes of the healing of the trauma were observed by hematoxylin-eosin staining.The expression of CD31 on the trauma was observed by immunohistochemistry. RESULTS AND CONCLUSION:(1)Human amniotic mesenchymal stem cells overexpressing neuregulin-1 were successfully constructed.The mRNA and protein expression of intracellular neuregulin 1 was significantly up-regulated compared with the empty group(P<0.05).(2)The overexpression of neuregulin 1 promoted the migratory ability(P<0.01)and proliferative ability of human amniotic mesenchymal stem cells(P<0.05).(3)Human amniotic mesenchymal stem cells overexpressing neuregulin 1 promoted wound healing in mice(P<0.05)and wound angiogenesis(P<0.05).The results showed that overexpression of neuregulin 1 resulted in an increase in the proliferative and migratory capacities of human amniotic mesenchymal stem cells,significantly promoting wound healing and angiogenesis.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To evaluate safety and clinical effect of Ommaya reservoir combined with external ventricular drainage for intraventricular hematoma(IVH),and to analyze the effects on neurological recovery,blood-brain-barrier(BBB)protection and the incidence of complications.Methods A total of 100 patients admitted to Yichun People's Hospital of Jiangxi Province for IVH and underwent surgical treatment from January 2021 to January 2023 were selected as the study subjects.Using a random number table,the patients were divided into control group(n=50)and treatment group(n=50).The treatment group received Ommaya reservoiv combined with external ventricular drainage,while the control group received conventional external ventricular drainage.The postoperative improvement rate,neurological recovery,BBB index,S100 calcium binding protein beta(neural)(S100β),myelin basic protein(MBP)levels,and hematoma clearance rate were compared between two groups.The incidence of complications in both groups was monitored over a 24-month follow-up period.Results At 3d,7d,and 14d post-surgery,the hematoma clearance rate in treatment group was higher than that in control group.At 3,12,and 24 months post-surgery,the patients of treatment group showed a higher improvement rate then that of control group,with better performance in National Institutes of Health stroke scale and Canadian stroke scale scores for neurological recovery,all differences being statistically significant(P＜0.05).During follow-ups at 1,3,12,and 24 months post-surgery,the BBB index,S100β,and MBP levels in treatment group were all lower than those in the control group,with all differences being statistically significant(P＜0.05).At 24 months post-surgery,the patients of treatment group had a lower incidence of complications than that of control group(P＜0.05).Conclusion Ommaya reservoir combined with exteral ventricular drainage can significantly improve neurological function,protect the BBB,and show good long-term efficacy in follow-up.

Objective:To investigate the situation of computed tomography(CT)equipment and socio economic development of various grades and classifications of medical institutions in Jiangsu Province,and to analyze the interrelationship between them.Methods:From October 20,2023 to November 20,2023,a questionnaire survey was conducted on imported and domestic CT equipment of various grades and classifications of medical institutions in 13 prefecture-level cities in Jiangsu Province through online questionnaire survey of"questionnaire star".The gross domestic product(GDP)of each prefecture-level city in Jiangsu province was used as an indicator of measuring the level of socio-economic development in the region.The CT number,the row number of detector,quality of image,the total examination case number of daily average and the daily average case number of single machine examination of medical institutions of various grades and classifications of 13 prefecture-level cities were used to conduct correlation analysis with GDP values of various districts.Results:A total of 910 questionnaires were distributed,and 512 questionnaires were retrieved.There were 482 valid questionnaires in the 512 questionnaires,and the valid rate was 94.15,which involved to 482 various grade and classification institutions of 13 prefecture-level cities in Jiangsu province.The number of imported and domestic CT equipment in the 13 prefecture-level cities of Jiangsu Province positively correlated with the GDP of each city(r=0.882,0.880,P<0.001).The number of imported CT equipment with 64 rows and more than 64 rows,and with less than 64 rows,and the number of domestic CT equipment with 64 rows and more than 64 rows,and with less than 64 rows all positively correlated with the GDP of each city(r=0.880,0.881,0.736,0.897,P<0.05).The total number of daily average of examinations for imported and domestic CT equipment of 13 prefecture-level cities positively correlated with the GDP of each city(r=0.774,0.814,P<0.05).There were no significant difference in the image quality and the daily average case number of single machine examination between the domestic CT equipment and the imported CT equipment(P>0.05).Conclusion:The medical institutions of city with high level of economic development have more quantitative and more high-end CT equipment,and the quality of image of domestic CT equipment is equal to that of imported CT equipment regardless of the high and low level of economic development.

Objective:To summarize the clinical characteristics of invasive Group A Streptococcus (GAS) infection in children and to provide reference for its clinical treatment and diagnosis. Methods:The medical records of inpatients whose sterile body fluids tested positive for GAS in Beijing Children′s Hospital from February 2013 to June 2024 were reviewed in this case series study.The clinical information of the patients was collected and summarized as a case report.Non-normally distributed measurement data were represented by the median ( M), and count data were represented by cases (%). Results:There were 42 cases of invasive GAS infection, with a median age of 6 years and 3 months (range: 14 days to 13 years and 7 months).Twenty-seven patients (64.3%) developed this disease in winter.In terms of susceptibility factors, there were 4 cases of trauma, 2 cases of influenza A, 1 case of neuroblastoma chemotherapy myelosuppression, 1 case of acute lymphoblastic leukemia chemotherapy myelosuppression, 1 case of varicella, and 1 case of scald among these 42 patients, there are no other obvious susceptibility factors.The types of specimens in which GAS was detected included 23 blood specimens, 9 pleural effusions, 9 sterile-site pus specimens, and 5 cerebrospinal fluids.GAS was detected in 4 children from two types of specimens simultaneously.The methods for detecting GAS included bacterial culture in 35 cases and next-generation sequencing in 9 cases.Two children tested positive for GAS by both methods.According to clinical diagnoses, there were 17 cases of pneumonia, 13 cases of streptococcus toxic shock syndrome, 10 cases of purulent meningitis, 6 cases of purulent osteomyelitis, 6 cases of purulent arthritis, 5 cases of cellulitis, 3 cases of necrotizing fasciitis, 2 cases of infectious myositis, and 2 cases of cervical abscess.Two or more clinical manifestations were detected in 26 patients.Drug sensitivity reports were available for 26 cases.All strains were sensitive to Penicillin, Vancomycin, Linezolid, Ceftriaxone and Cefepime.All except 2 were resistant to Clindamycin, and all were resistant to Erythromycin.All 42 cases were treated with intravenous antibiotics, and 21 of them also received human immunoglobulin.Three of the patients died and 39 were discharged from hospital. Conclusions:Pediatric invasive GAS infection occurs mainly in winter and manifests as pneumonia, purulent meningitis, purulent osteomyelitis, and purulent arthritis.The strains are sensitive to β-lactam antibiotics, Vancomycin and Linezolid, and most are resistant to Clindamycin and Erythromycin.

Objective:To summarize the clinical characteristics of invasive Group A Streptococcus (GAS) infection in children and to provide reference for its clinical treatment and diagnosis. Methods:The medical records of inpatients whose sterile body fluids tested positive for GAS in Beijing Children′s Hospital from February 2013 to June 2024 were reviewed in this case series study.The clinical information of the patients was collected and summarized as a case report.Non-normally distributed measurement data were represented by the median ( M), and count data were represented by cases (%). Results:There were 42 cases of invasive GAS infection, with a median age of 6 years and 3 months (range: 14 days to 13 years and 7 months).Twenty-seven patients (64.3%) developed this disease in winter.In terms of susceptibility factors, there were 4 cases of trauma, 2 cases of influenza A, 1 case of neuroblastoma chemotherapy myelosuppression, 1 case of acute lymphoblastic leukemia chemotherapy myelosuppression, 1 case of varicella, and 1 case of scald among these 42 patients, there are no other obvious susceptibility factors.The types of specimens in which GAS was detected included 23 blood specimens, 9 pleural effusions, 9 sterile-site pus specimens, and 5 cerebrospinal fluids.GAS was detected in 4 children from two types of specimens simultaneously.The methods for detecting GAS included bacterial culture in 35 cases and next-generation sequencing in 9 cases.Two children tested positive for GAS by both methods.According to clinical diagnoses, there were 17 cases of pneumonia, 13 cases of streptococcus toxic shock syndrome, 10 cases of purulent meningitis, 6 cases of purulent osteomyelitis, 6 cases of purulent arthritis, 5 cases of cellulitis, 3 cases of necrotizing fasciitis, 2 cases of infectious myositis, and 2 cases of cervical abscess.Two or more clinical manifestations were detected in 26 patients.Drug sensitivity reports were available for 26 cases.All strains were sensitive to Penicillin, Vancomycin, Linezolid, Ceftriaxone and Cefepime.All except 2 were resistant to Clindamycin, and all were resistant to Erythromycin.All 42 cases were treated with intravenous antibiotics, and 21 of them also received human immunoglobulin.Three of the patients died and 39 were discharged from hospital. Conclusions:Pediatric invasive GAS infection occurs mainly in winter and manifests as pneumonia, purulent meningitis, purulent osteomyelitis, and purulent arthritis.The strains are sensitive to β-lactam antibiotics, Vancomycin and Linezolid, and most are resistant to Clindamycin and Erythromycin.

Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725～0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.