Objective:To analyze the human immunodeficiency virus (HIV) screening status and the resulting residual risk (RR) among blood donors across 17 provincial blood centers in China.Methods:This study used a cross-sectional study. Data on HIV infection markers per 100 000 first-time donors (FD) and repeat donors (RD) from January 2015 to December 2024 were extracted from the National Blood Establishment Performance Comparison Information Management System. Questionnaires were used to collect each center′s HIV screening strategy, algorithm, serological test (ST) kit manufacturers, gray-zone setting for ST, and nucleic acid test (NAT) modality, method, and platform. The incidence-window-period model was used to calculate the residual risk for first-time donors (RR FD), repeat donors (RR RD), and total donors (RR TD) at each center. Horizontal and vertical analysis of RR FD, RR RD, and RR TD across centers and years were performed. Results:All 17 centers applied the same HIV screening strategy which was two rounds of ST followed by one round of NAT. Eight of them operated a single screening algorithm, six employed two algorithms and three used three. Eleven centers used both imported and domestic ST kits, five relied on domestic ST kits only, and one used imported ST kits only, while four centers never set a grey zone for ST throughout the decade. For NAT modalities, eight centers adopted both individual nucleic acid test (ID-NAT) and minipool nucleic acid test (MP-NAT), eight used MP-NAT only and one used ID-NAT only. Seven centers combined transcription mediated amplification (TMA) and polymerase chain reaction (PCR), nine used PCR only and one used TMA only, and fourteen centers ran both imported and domestic NAT systems, two used imported systems only and one used a domestic system only. Over the ten-year period, the mean RR FD across the centers ranged from 2.22 to 12.33 per 10 6 person-years, RR RD from 0.83 to 3.29 per 10 6 person-years and RR TD from 1.59 to 9.29 per 10 6 person-years, with center Z4 consistently showing the lowest values for all three metrics and center U4 recording the highest RR FD and RR TD, while center D2 had the highest RR RD. In 2024 compared with 2015, eleven centers achieved a lower RR FD and ten centers achieved lower RR RD and RR TD. The RR FD and RR TD of centers W2 and U4 displayed pronounced fluctuations and an upward trend in recent years. Conclusions:The 17 provincial blood centers maintain consistent HIV screening strategies, while demonstrating variations in screening algorithm, ST kit manufacturers, NAT modalities, methods, and platform. And the RR FD, RR RD, and RR TD differ across centers. Although most centers show declining trend in RR over the ten-year period, some centers exhibite data fluctuations with a rising trend, suggesting potential for further optimization of HIV screening protocols.

Locomotion, a fundamental motor function encompassing various forms such as swimming, walking, running, and flying, is essential for animal survival and adaptation. The mesencephalic locomotor region (MLR), located at the midbrain-hindbrain junction, is a conserved brain area critical for controlling locomotion. This review highlights recent advances in understanding the MLR’s structure and function across species, from lampreys to mammals and birds, with a particular focus on insights gained from optogenetic studies in mammals. The goal is to uncover universal strategies for MLR-mediated locomotor control. Electrical stimulation of the MLR in species such as lampreys, salamanders, cats, and mice initiates locomotion and modulates speed and patterns. For example, in lampreys, MLR stimulation induces swimming, with increased intensity or frequency enhancing propulsive force. Similarly, in salamanders, graded stimulation transitions locomotor outputs from walking to swimming. Histochemical studies reveal that effective MLR stimulation sites colocalize with cholinergic neurons, suggesting a conserved neurochemical basis for locomotion control. In mammals, the MLR comprises two key nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). Both nuclei contain glutamatergic and GABAergic neurons, with the PPN additionally housing cholinergic neurons. Optogenetic studies in mice by selectively activating glutamatergic neurons have demonstrated that the CnF and PPN play distinct roles in motor control: the CnF drives rapid escape behaviors, while the PPN regulates slower, exploratory movements. This functional specialization within the MLR allows animals to adapt their locomotion patterns and speed in response to environmental demands and behavioral objectives. Similar to findings in lampreys, the CnF and PPN in mice transmit motor commands to spinal effector circuits by modulating the activity of brainstem reticular formation neurons. However, they achieve this through distinct reticulospinal pathways, enabling the generation of specific behaviors. Further insights from monosynaptic rabies viral tracing reveal that the CnF and PPN integrate inputs from diverse brain regions to produce context-appropriate behaviors. For instance, glutamatergic neurons in the PPN receive signals from other midbrain structures, the basal ganglia, and medullary nuclei, whereas glutamatergic neurons in the CnF rarely receive inputs from the basal ganglia but instead are strongly influenced by the periaqueductal grey and inferior colliculus within the midbrain. These differential connectivity patterns underscore the specialized roles of the CnF and PPN in motor control, highlighting their unique contributions to coordinating locomotion. Birds exhibit exceptional flight capabilities, yet the avian MLR remains poorly understood. Comparative studies suggest that the pedunculopontine tegmental nucleus (PPTg) in birds is homologous to the mammalian PPN, which contains cholinergic neurons, while the intercollicular nucleus (ICo) or nucleus isthmi pars magnocellularis (ImC) may correspond to the CnF. These findings provide important clues for identifying the avian MLR and elucidating its role in flight control. However, functional validation through targeted experiments is urgently needed to confirm these hypotheses. Optogenetics and other advanced techniques in mice have greatly advanced MLR research, enabling precise manipulation of specific neuronal populations. Future studies should extend these methods to other species, particularly birds, to explore unique locomotor adaptations. Comparative analyses of MLR structure and function across species will deepen our understanding of the conserved and evolved features of motor control, revealing fundamental principles of locomotion regulation throughout evolution. By integrating findings from diverse species, we can uncover how the MLR has been adapted to meet the locomotor demands of different environments, from aquatic to aerial habitats.

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.

Objective:To analyze the human immunodeficiency virus (HIV) screening status and the resulting residual risk (RR) among blood donors across 17 provincial blood centers in China.Methods:This study used a cross-sectional study. Data on HIV infection markers per 100 000 first-time donors (FD) and repeat donors (RD) from January 2015 to December 2024 were extracted from the National Blood Establishment Performance Comparison Information Management System. Questionnaires were used to collect each center′s HIV screening strategy, algorithm, serological test (ST) kit manufacturers, gray-zone setting for ST, and nucleic acid test (NAT) modality, method, and platform. The incidence-window-period model was used to calculate the residual risk for first-time donors (RR FD), repeat donors (RR RD), and total donors (RR TD) at each center. Horizontal and vertical analysis of RR FD, RR RD, and RR TD across centers and years were performed. Results:All 17 centers applied the same HIV screening strategy which was two rounds of ST followed by one round of NAT. Eight of them operated a single screening algorithm, six employed two algorithms and three used three. Eleven centers used both imported and domestic ST kits, five relied on domestic ST kits only, and one used imported ST kits only, while four centers never set a grey zone for ST throughout the decade. For NAT modalities, eight centers adopted both individual nucleic acid test (ID-NAT) and minipool nucleic acid test (MP-NAT), eight used MP-NAT only and one used ID-NAT only. Seven centers combined transcription mediated amplification (TMA) and polymerase chain reaction (PCR), nine used PCR only and one used TMA only, and fourteen centers ran both imported and domestic NAT systems, two used imported systems only and one used a domestic system only. Over the ten-year period, the mean RR FD across the centers ranged from 2.22 to 12.33 per 10 6 person-years, RR RD from 0.83 to 3.29 per 10 6 person-years and RR TD from 1.59 to 9.29 per 10 6 person-years, with center Z4 consistently showing the lowest values for all three metrics and center U4 recording the highest RR FD and RR TD, while center D2 had the highest RR RD. In 2024 compared with 2015, eleven centers achieved a lower RR FD and ten centers achieved lower RR RD and RR TD. The RR FD and RR TD of centers W2 and U4 displayed pronounced fluctuations and an upward trend in recent years. Conclusions:The 17 provincial blood centers maintain consistent HIV screening strategies, while demonstrating variations in screening algorithm, ST kit manufacturers, NAT modalities, methods, and platform. And the RR FD, RR RD, and RR TD differ across centers. Although most centers show declining trend in RR over the ten-year period, some centers exhibite data fluctuations with a rising trend, suggesting potential for further optimization of HIV screening protocols.

Objective:To investigate the influencing of preoperative total bilirubin (TBil) on perioperative complications of hepatolithiasis receiving liver resection.Methods:The retrospective cohort study was conducted. The clinical data of 300 patients with hepatolithiasis who were admitted to 2 medical centers from January 2010 to January 2022 were collected. There were 115 males and 185 females, aged (54±13)years. Measurement data with normal distribution were represented as Mean± SD, and the independent sample t test was used for comparison between groups. Measurement data with skewed distribution were represented as M( Q1, Q3), and the Mann-Whitney U test was used for comparison between groups. Count data were expressed as absolute numbers, and the chi-square test was used for comparison between groups. Variables with P<0.10 in the univariate analysis were included into the multivariate analysis. Univariate analysis was conducted using the Logistic regression model,and multivariate analysis was conducted using the Logistic stepwise regression model with backward Wald method. Continuous variables were converted into categorical variables based on commonly reported cutoff values when conducting Logistic regression analysis. Results:(1) Comparison of clinical data of patients with different preoperative TBil. Of 300 patients with hepatolithiasis, there were 252 cases with low level of preoperative TBil as 14.4(11.1,19.7)μmol/L, and there were 48 cases with high level of preoperative TBil as 44.0(31.3,59.8)μmol/L. Of the pati-ents with low level of preoperative TBil, neutrophils percentage was 62%±10%, cases with intra-operative blood transfusion was 29, and cases undergoing anatomical liver resection was 166. Of the patients with high level of preoperative TBil, neutrophils percentage was 70%±11%, cases with intraoperative blood transfusion was 22, and cases undergoing anatomical liver resection was 15. There were significant differences in cases classified as>grade 2 of ASA classification, neutrophils percentage, cases with intraoperative blood transfusion and cases undergoing anatomical liver resection between patients with low and high level of preoperative TBil ( t=5.182, χ2=33.669, 18.775, P<0.05). (2) Comparison of perioperative complications of patients with different preoperative TBil. Of the 252 patients with low level of TBil, there were 151 cases with complications including 35 cases of serious complications, there was 1 case with postoperative liver failure, the duration of postoperative hospital stay was 13.0(10.0,16.0)days. Of the 48 patients with high level of TBil, there were 32 cases with complications including 17 cases of serious complications, there were 6 cases with postoperative liver failure, the duration of postoperative hospital stay was 14.0(10.0,18.8)days. There were significant differences in cases with serious complications and cases with postoperative liver failure between patients with low and high level of preoperative TBil ( χ2=13.041, 20.879, P<0.05). (3) Analysis of factors influencing postoperative serious complications in patients undergoing liver resection. Results of multivariate analysis showed that age, body mass index (BMI), preoperative TBil and volume of intraoperative blood loss were independent factors influencing postoperative serious complications in patients undergoing liver resection for hepatolithiasis ( odds ratio=3.852, 2.358, 2.935, 5.135, 95% confidence interval as 1.478?9.979, 1.110?5.009, 1.398?6.158, 2.088?12.626, P<0.05). Conclusions:Patients with high level of preoperative TBil have a significantly increased risk of postoperative serious complications and liver failure who receive liver resection for hepatolithiasis. Age, preoperative BMI, TBil and volume of intraoperative blood loss are independent factors influencing postoperative serious complications in patients undergoing liver resection for hepatolithiasis.

Nitazenes are a class of synthetic opioids that have recently emerged in the illegal drug market.They are characterized by high potency and a narrow therapeutic window.Compared with tradi-tional opioids,these substances are more likely to cause severe respiratory depression.In recent years,the abuse of nitazenes has occurred frequently,causing hundreds of overdose deaths worldwide,and posing a serious threat to individual health and public safety.As more nitazenes continue to emerge,research on the identification of these substances has received increasing attention.This paper reviews the structural characteristics,in vivo and in vitro pharmacological characterizations and analysis methods of common nitazenes,aiming to provide a basis and reference for the study of these substances in fo-rensic toxicology.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the role of p-AKT-mTOR-P70S6K signaling pathway in radiation therapy for polyploid cervical cancer cells.Methods:Human cervical cancer HeLa cell lines were selected and HeLa cells were radiated under 7 Gy of 6 MV X-ray. The morphological changes of the cells were observed with an inverted microscope on day 5 after radiation induction. All cells were divided into the 7 Gy group (7 Gy X-ray radiation but not transfected polyploidy HeLa cells) and the control group (the non-radiation-induced and not transfected HeLa cells). In addition, the plasmid carrying pcDNA3 negative control sequence and the plasmid carrying pcDNA3-TT-AKT sequence were transfected into HeLa cells, respectively, which were induced by 7 Gy X-ray radiation after 48 h of transfection, and then they were recorded as the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group. Cell proliferation ability was detected by using CCK-8 assay, cell cycle was detected by using flow cytometry, cell apoptosis was detected by using mitochondrial membrane potential assay, the relative expression levels of cell proliferation, cell cycle, apoptosis and autophagy related proteins were tested by using Western blot.Results:Most of the normal HeLa cells in the 7 Gy group died on day 5 after radiation induction, and only a few surviving cells increased in size with multiple nuclei. The results of Western blot showed that the relative expression levels of p-AKT, p-mTOR and p-P70S6K in HeLa cells of the 7 Gy group were lower than those of the control group (all P < 0.05). CCK-8 assay showed that the absorbance ( A) values were 0.45±0.06, 0.65±0.06 after 48 h of culture and 0.75±0.05, 1.05±0.02 after 72 h of culture, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the differences were statistically significant (all P < 0.05), and the A values in the pcDNA3-TT-AKT + 7 Gy group were all higher than those in the pcDNA3 +7 Gy group. Flow cytometry results showed that the proportion of cells was (29.2±3.6)%, (26.7±1.7)% in G 0/G 1 phase and (29.6±1.6)%, (30.3±0.6)% in G 2/M phase, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the differences were not statistically significant (all P > 0.05); the proportion of cells in S phase was (10.2±0.9)% and (14.6±1.5)%, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the differences were statistically significant ( t = 2.86, P = 0.043). Mitochondrial membrane potential assay showed that the green fluorescence proportion was (23.1±2.5)% and (14.3±1.9)%, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the different was statistically significant ( t = 4.82, P = 0.009). Western blot results showed that the relative expression level of p-cdc25c (Ser216) in the pcDNA3-TT-AKT+7 Gy group was higher than that in the pcDNA3+7 Gy group ( P < 0.001); and the relative expression levels of Bak and LC3-Ⅱ/Ⅰ in the pcDNA3-TT-AKT+7Gy group were lower than those in the pcDNA3 +7 Gy group, respectively (all P < 0.05). Conclusions:The p-AKT-mTOR-P70S6K signaling pathway may be involved in the regulation of radiation-induced polyploidy HeLa cell proliferation, cell cycle and cell apoptosis.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*