Objective: To investigate the effects of clinical routine X-ray irradiation dose (average irradiation dose: 29.7±0.54 Gy) on the function, apoptosis, activation state and mitochondrial function of platelets during in vitro storage, so as to provide experimental evidence for optimizing platelet irradiation strategies. Methods: A paired experimental design was adopted. Platelets were collected from 12 healthy donors, and each sample was equally divided into the irradiated group and the control group (non-irradiated). All samples were stored for 5 days under standard platelet preservation conditions (22±2℃, continuous oscillation). Flow cytometry was used to detect platelet count, apoptosis rate (Annexin V+ positive rate), activation markers (CD62P, PAC-1, CD42b) and reactive oxygen species (ROS) level. Meanwhile, mitochondrial-specific probes were used to evaluate changes in mitochondrial count, membrane potential and adenosine triphosphate (ATP) content. Additionally, transmission electron microscopy (TEM) was employed to observe the ultrastructure of platelets, with a focus on mitochondrial morphology, platelet membrane integrity and granule distribution. Results: Within 5 days of storage, the platelet count was (841±89.16)×10 /L in the irradiated group and (824.5±92.88)×10 /L in the control group, with no statistically significant difference between the two groups (P=0.54). The apoptosis rate was (4.94±1.39) % in the irradiated group and (5.50±0.83) % in the control group, showing no significant difference (P=0.31). For activation indicators, the CD62P expression rate was (24.32±7.57) % in the irradiated group versus (25.21±8.13) % in the control group (P=0.43). The PAC-1 positive rates were (12.15±4.43) % and (11.75±3.40) % in the irradiated group and control group, respectively (P=0.44). The CD42b expression rates were (12.14±4.43) % and (11.75±3.4) % in the two groups, respectively (P=0.47). The ROS levels were (31.98±8.1) % and (30.64±5.89) % in the two groups, respectively (P=0.45). No significant differences were found in the above indicators. For mitochondrial function indicators, the mitochondrial count was (55.88±11.49) % in the irradiated group and (53.5±7.24) % in the control group (P=0.57). The ATP contents were (42.45±5.29) % and (41.58±9.50) % in the irradiated group and control group, respectively (P=0.77). The relative membrane potential values were (59.53±10.89) % and (57.49±6.54) % in the two groups, respectively (P=0.47). No significant difference were observed on the mitochondrial function-related indicators. TEM further confirmed that the ultrastructure of platelets in the irradiation group was intact, the mitochondrial morphology was normal, and no pathological changes such as swelling or vacuolization were observed. Conclusion: This study evaluated the impact of conventional-dose X-ray irradiation on platelet storage quality, confirming that this dose does not significant impair platelet count, apoptosis rate, activation status, or mitochondrial function. This finding provides important experimental evidence for the clinical promotion of X-ray irradiation technology and suggests its potential as a safe alternative to γ irradiation. Future studies could further expand the sample size and extend the observation period to verify the effects of X-ray irradiation on long-term platelet storage and post-transfusion in vivo survival rate.

Objective: To validate the performance of the Procleix UltrioPlex E assay (Grifols, Spain) on the Procleix Panther automated nucleic acid detection platform, which employs the TMA method to simultaneously detect HIV-1/HIV-2/HCV/HBV/HEV viruses, and to evaluate its value for screening transfusion-associated infectious diseases. Methods: In accordance with the requirements of ISO15189"Application of the Guidelines for the Accreditation of Quality and Capabilities of Medical Laboratories in the Field of Molecular Diagnostics (CNAS-CL02-A009: 2018)", "Guidelines for Performance Validation of Molecular Diagnostic Testing Procedures (CNAS-GL039: 2019)", and the "Technical Operating Procedures for Blood Banks (2019 Edition)", this study validated the reagent's performance in terms of analytical sensitivity validation, performance consistency validation, interference resistance, and cross-contamination resistance. Results: Probit analysis revealed that the 95% detection limits (95% confidence interval) for HBV, HCV, HIV, and HEV were 2.0 IU/mL, 1.5 IU/mL, 18.0 IU/mL and 3.7 IU/mL, respectively, which were consistent with the minimum detection limits stated in the kit's package insert and were comparable to the Procleix Ultrio Elite kit. Both kits were used to test the performance validation serum plate simultaneously, yielding results consistent with the serum plate (Kappa=1), indicating stable performance. Detection of medium-and low-concentration lipemia and weakly positive hemolysis samples demonstrated good interference resistance. Cross-contamination performance validation showed that the kit exhibited excellent cross-contamination resistance. Conclusion: The Procleix UltrioPlex E nucleic acid detection kit enables combined detection of HIV-1, HIV-2, HCV, HBV, and HEV, allowing single-test screening for multiple viruses in donor blood. The kit's analytical performance is stable and meets basic laboratory requirements, making it suitable for screening transfusion-associated infectious diseases in blood banks.

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVE: To explore the safety and efficacy of high-dose etoposide (VP-16) combined with recombinant human granulocyte colony-stimulating factor (rhG-CSF) as salvage mobilization for peripheral blood stem cells (PBSC) in newly diagnosed multiple myeloma (NDMM) patients. METHODS: From April 2021 to May 2023, eight NDMM patients who had failed to yield sufficient PBSC during initial mobilization with high-dose cyclophosphamide (CTX) combined with rhG-CSF underwent salvage mobilization with 1.2 g/m2 etoposide combined with rhG-CSF 10 μg/(kg·d). The effects and adverse reactions of initial mobilization and salvage mobilization were analyzed. RESULTS: For salvage mobilization and initial mobilization, the numbers of PBSC collections were 16 and 18, respectively. The mean value of total collected CD34⁺ cells were (11.90±5.75)×10⁶/kg and (1.67±0.75)×10⁶/kg (P =0.0010) in salvage mobilization group and initial mobilization group, respectively. The proportion of patients with a total collection of CD34⁺ cell count≥2×10⁶/kg were 100% and 37.5% (P =0.0625), and the proportion of patients with a total collection of CD34⁺ cell count≥5×10⁶/kg were 87.5% and 0% (P =0.0156) in salvage mobilization group and initial mobilization group, respectively. For five patients who underwent high-dose CTX initial mobilization but had a total CD34⁺ cell count < 2×10⁶/kg, successful collection was achieved through salvage mobilization with high-dose VP-16. Salvage mobilization with high-dose VP-16 was scheduled 2-3 weeks after failure of CTX mobilization. Adverse reactions of high-dose VP-16 mobilization did not increase compared to the initial mobilization with high-dose CTX. CONCLUSION As a salvage mobilization regimen, VP-16 1.2 g/m² combined with rhG-CSF is safe and highly effective in NDMM patients who failed to initial mobilization with high-dose CTX combined with rhG-CSF.
Humans ; Multiple Myeloma/therapy* ; Etoposide/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Cyclophosphamide/therapeutic use* ; Granulocyte Colony-Stimulating Factor ; Salvage Therapy ; Peripheral Blood Stem Cells ; Male ; Middle Aged ; Female ; Peripheral Blood Stem Cell Transplantation

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Objective:To construct a predictive model for urinary tract infection in patients with cervical spine fracture based on the random forest (RF) algorithm and evaluate its predictive performance.Methods:A retrospective cohort study was conducted to analyze the clinical data of 400 patients with cervical spine fracture admitted to West China Hospital of Sichuan University from October 2020 to February 2025, including 311 males and 89 females, aged 12-87 years [(48.5±14.8)years]. According to the occurrence of urinary tract infection during hospital stay, the patients were divided into urinary tract infection group ( n=57) and non-urinary tract infection group ( n=343). General information, disease-related data, and serological laboratory indicators during hospital stay were recorded in both groups. Viriables for urinary tract infection in patients with cervical spine fracture were analyzed and identified through univariate analysis and Lasso regression analysis. Using the bootstrap method with 500 resamples, the data were randomly allocated into the training set ( n=281) and test set ( n=119) at a ratio of 7∶3. An RF prediction model for urinary tract infection in patients with cervical spine fracture was constructed in the training set and the variable importance for the model was calculated. The constructed RF prediction model was validated in the test set, with the predictive accuracy, sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC) calculated to evaluate its predictive performance. Results:Univariate analysis showed that age, body mass index (BMI), length of hospital stay, concurrent hepatic impairment, concurrent benign prostatic hyperplasia, indwelling catheterization, duration of indwelling catheterization, immunosuppressant use, fracture site, cervical spinal cord injury, Frankel grade, time from injury to surgery, red blood cell count (RBC), hemoglobin (Hb), white blood cell count (WBC), albumin (Alb), globulin (GLO), blood urea nitrogen (BUN), and C-reactive protein (CRP) were significantly associated with urinary tract infection in patients with cervical spine fracture ( P<0.05). Among them, 9 viriables screened through Lasso regression analysis were age, length of hospital stay, concurrent hepatic impairment, concurrent benign prostatic hyperplasia, indwelling catheterization, duration of indwelling catheterization, Frankel grade, time from injury to surgery, and RBC. Based on the 9 viriables, a predictive model for urinary tract infection in patients with cervical spine fracture was constructed using the RF algorithm. Based on the mean decrease in Gini coefficient in the RF model, the top 6 important variables were duration of indwelling catheterization, length of hospital stay, RBC, age, time from injury to surgery, and Frankel grade in sequence. In the test set, the model achieved a prediction accuracy of 87.4%, sensitivity of 88.2%, specificity of 82.4%, and AUC of 0.89 (95% CI 0.80, 0.93). Conclusion:The RF prediction model for urinary tract infection in patients with cervical spine fracture is constructed based on 9 predictors including duration of indwelling catheterization, length of hospital stay, RBC, age, time from injury to surgery, Frankel grade, concurrent hepatic impairment, concurrent benign prostatic hyperplasia, and indwelling catheterization, with the first 6 viriables ranked as the most important factors, and demonstrates favorable predictive performance.

Objective:To investigate the use of non-vitamin K antagonist oral anticoagulants(NOACs)and their associated comorbidities in patients aged 80 years and older with non-valvular atrial fibrillation(NVAF), as well as to understand the challenges faced by elderly patients receiving NOAC therapy.Methods:We retrospectively enrolled elderly patients(≥80 years old)with NVAF who were treated with NOACs at a hospital in Beijing from January 2018 to August 2023.Patients were categorized into two age groups: 80-89 years and ≥90 years.We collected baseline data, including demographic characteristics, details of atrial fibrillation, comorbidities, laboratory test results, and medication combinations, for descriptive statistical analysis and intergroup comparisons.Results:A total of 695 elderly patients with NVAF receiving NOACs were included in the study, with a median age of 84 years.Among these patients, there were 328 males(47.19%, 328/695)and 422 cases of paroxysmal atrial fibrillation(60.72%, 422/695).The age group of 80-89 years comprised 640 cases(92.09%, 640/695), while the group aged 90 years and above included 55 cases(7.91%, 55/695).The use of NOACs in patients aged 90 and older exhibited an increasing trend over the years.Inter-group comparisons indicated that the ≥90 years group had lower body mass index, longer hospital stays, increased bedridden time, poorer renal function, lower levels of albumin and hemoglobin, and higher D-dimer levels.Inappropriate dosing of DOACs occurred in 49.64%(345/695)of cases, with 90.72%(313/345)receiving doses lower than recommended.Lower-than-recommended doses were more prevalent in the ≥90 years group, while higher-than-recommended doses were more common in the 80-89 years group.Polypharmacy was noted in 61.29%(426/695)of patients.The concurrent use of antiplatelet drugs, rhythm control medications, and ventricular rate control drugs was observed in 12.52%(87/695), 19.57%(136/695), and 54.53%(379/695)of patients, respectively, with no significant differences between groups.Conclusions:Inappropriate dosing and polypharmacy are prevalent issues among elderly NVAF patients.Therefore, it is essential to enhance multidisciplinary collaboration to optimize anticoagulation treatment strategies.

ObjectiveTo study the effect of the herb pair Mori Folium-Ginseng Radix et Rhizoma （HMG） on glucose and lipid metabolism in the mouse model of type 2 diabetes mellitus and decipher the possible treatment mechanism. MethodsThe db/db mice were chosen as the mouse model of type 2 diabetes mellitus and then treated with HMG at low and high doses （1.56， 3.12 g∙kg^-1， respectively） or metformin （0.26 g∙kg^-1） by gavage for 6 weeks. The normal group and the model group were treated with double distilled water at the same time according to body weight. The 8-h fasting blood glucose and body weight were measured once a week. The oral glucose tolerance test （OGTT） was conducted at the 6th week of dosing. The mice were sacrificed after the end of dosing. Serum levels of lipids ［total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL）， and low-density lipoprotein cholesterol （LDL）］， liver function indicators ［aspartate aminotransferase （AST） and alanine aminotransferase （ALT）］， non-esterified fatty acids （NEFA）， glycosylated serum protein （GSP）， serum glucose （GLU）， fasting insulin （FINS）， and renal function indicators ［creatinine （Crea） and blood urea nitrogen （BUN）］ were measured by enzyme-linked immunosorbent assay. The protein levels of peroxidase proliferator-activating receptor gamma （PPARγ）， acetyl coenzyme A carboxylase （ACC）， and sterol regulatory element-binding protein-1 （SREBP-1） were determined by Western blot. The pathological changes in the liver and pancreas were examined. ResultsCompared with the normal group， the model group presented increased body weight， elevated levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， GSP， and HDL-C， up-regulated protein levels of ACC and SREBP-1， and down-regulated protein level of PPARγ （P<0.01）. Meanwhile， the model group presented a large amount of lipid droplets and steatosis in the liver， as well as karyopyknosis and lymphocyte infiltration in the pancreas. Compared with the model group， the high- and low-dose HMG groups showed decreased body weight， declined levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， and GSP， and elevate level of HDL-C （P<0.05， P<0.01）. Moreover， the two groups showcased reduced lipid droplets and steatosis in the liver， as well as enlarged islets with clear boundaries and alleviated lymphocyte infiltration and karyopyknosis. Western blot results showed that the high-dose herb pair group demonstrated down-regulated protein levels of ACC and SREBP-1 and up-regulated protein level of PPARγ （P<0.01）. ConclusionThe HMG can effectively improve the glucose and lipid metabolism in db/db mice by regulating the expression of PPARγ， SREBP-1， and ACC.

ObjectiveTo study the effect of the herb pair Mori Folium-Ginseng Radix et Rhizoma （HMG） on glucose and lipid metabolism in the mouse model of type 2 diabetes mellitus and decipher the possible treatment mechanism. MethodsThe db/db mice were chosen as the mouse model of type 2 diabetes mellitus and then treated with HMG at low and high doses （1.56， 3.12 g∙kg^-1， respectively） or metformin （0.26 g∙kg^-1） by gavage for 6 weeks. The normal group and the model group were treated with double distilled water at the same time according to body weight. The 8-h fasting blood glucose and body weight were measured once a week. The oral glucose tolerance test （OGTT） was conducted at the 6th week of dosing. The mice were sacrificed after the end of dosing. Serum levels of lipids ［total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL）， and low-density lipoprotein cholesterol （LDL）］， liver function indicators ［aspartate aminotransferase （AST） and alanine aminotransferase （ALT）］， non-esterified fatty acids （NEFA）， glycosylated serum protein （GSP）， serum glucose （GLU）， fasting insulin （FINS）， and renal function indicators ［creatinine （Crea） and blood urea nitrogen （BUN）］ were measured by enzyme-linked immunosorbent assay. The protein levels of peroxidase proliferator-activating receptor gamma （PPARγ）， acetyl coenzyme A carboxylase （ACC）， and sterol regulatory element-binding protein-1 （SREBP-1） were determined by Western blot. The pathological changes in the liver and pancreas were examined. ResultsCompared with the normal group， the model group presented increased body weight， elevated levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， GSP， and HDL-C， up-regulated protein levels of ACC and SREBP-1， and down-regulated protein level of PPARγ （P<0.01）. Meanwhile， the model group presented a large amount of lipid droplets and steatosis in the liver， as well as karyopyknosis and lymphocyte infiltration in the pancreas. Compared with the model group， the high- and low-dose HMG groups showed decreased body weight， declined levels of blood glucose， TG， TC， AST， ALT， GLU， NEFA， and GSP， and elevate level of HDL-C （P<0.05， P<0.01）. Moreover， the two groups showcased reduced lipid droplets and steatosis in the liver， as well as enlarged islets with clear boundaries and alleviated lymphocyte infiltration and karyopyknosis. Western blot results showed that the high-dose herb pair group demonstrated down-regulated protein levels of ACC and SREBP-1 and up-regulated protein level of PPARγ （P<0.01）. ConclusionThe HMG can effectively improve the glucose and lipid metabolism in db/db mice by regulating the expression of PPARγ， SREBP-1， and ACC.

OBJECTIVES: To propose a hypothesis that aloe-emodin may inhibit scar tissue fibrosis through thrombospondin-1(THBS1)-PI3K-Akt pathway. METHODS: By cultivating fibroblasts derived from scar tissue after cleft palate surgery in humans, aloe emodin of different concentrations (10, 20, 30, 40 and 50 μmol/L) was added to the cells which activity was detected. At the same time, transcriptome sequencing was performed on scar tissue and cells, and bioinformatics methods were used to explore potential targets and signaling pathways of scar tissue fibrosis. RESULTS: Aloe-emodin had a concentration dependent inhibitory effect on fibroblast proliferation,with the 40 μmol/L concentration group showing the most significant effect. The results of tissue and cell sequencing indicated that differentially expressed genes were significantly enriched in extracellular matrix-receptor interaction pathway, and shared a common differential gene which was THBS1. The ORA analysis results indicated that differentially expressed genes, including THBS1, were significantly enriched in the PI3K-Akt signaling pathway. CONCLUSIONS Aloe emodin may inhibit the PI3K-Akt pathway by downregulating THBS1, thereby reducing the proliferation activity of fibroblasts derived from postoperative palatal scar tissue.
Thrombospondin 1/genetics* ; Humans ; Signal Transduction/drug effects* ; Fibroblasts/cytology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Fibrosis ; Phosphatidylinositol 3-Kinases/metabolism* ; Cicatrix/metabolism* ; Cell Proliferation/drug effects* ; Anthraquinones/pharmacology* ; Cells, Cultured