OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

In recent years， repetitive transcranial magnetic stimulation （rTMS） has garnered significant attention as a therapeutic approach for sleep disorders in the elderly. However， the prevailing rTMS protocols are predominantly developed based on normative neurophysiological data derived from young adults and fail to incorporate individualized parameters tailored to the brain characteristics of the elderly. To address this gap， the consensus development group synthesized the latest evidence from 2010 to 2025 and established a standardized rTMS protocol specifically for elderly patients with sleep disorders. Adhering to the Appraisal of Guidelines for Research and Evaluation II （AGREE II） framework， systematically screened randomized controlled trials （RCTs） and systematic reviews regarding rTMS in the treatment of sleep disorders across various conditions. Meanwhile， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system was employed to rigorously grade the quality of evidence and the strength of recommendations. This consensus guideline delineates precise rTMS protocols for the management of sleep disorders in the elderly， highlights the adjustment of stimulation intensity according to scalp-cortex distance recommends either MRI‑guided neuronavigation or the Beam F3/F4 heuristic approach for accurate target localization， thereby providing precise rTMS intervention protocol for sleep disorders in the elderly， aiming to enhance clinical efficacy while ensuring treatment safety. ［Funded by National Key Research and Development Program （number， 2023YFC3603200）； General Program of Shenzhen Science and Technology Innovation Commission （number， JCYJ20240813112859008， JCYJ20240813112900002）； Youth Program of Shenzhen Kangning Hospital （number， KN2023A004）； www.guidelines-registry.cn number， PREPARE-2026CN530］

Objective: To conduct screening for rare blood types within important blood group systems for the Chinese population, such as Rh, Duffy, Kidd, P1Pk, Diego, and MNS, in the Guangzhou region, and to establish a corresponding rare blood type database and physical repository. Methods: The saline medium microplate method was used to screen blood donors with the ccDEE phenotype combined with either Jk(a-) or Jk(b-). The polybrene microplate method was employed to screen for donors with Fy(a-), s(-), Lu(b-), Di(b-), k(-), and p phenotypes. The urea lysis microplate method was applied to screen for the Jk(a-b-) phenotype. A high-resolution melting (HRM) curve method was established for screening some donors with the Di(b-) phenotype. Subsequently, expanded phenotyping of antigens in the Rh, Kidd, MNS, Duffy, P1Pk, Lewis, Kell, and Lutheran blood group systems was performed on identified rare blood type donors using monoclonal antibodies. The test results are entered into the Rare Blood Type Bank Management System of the Guangzhou Blood Center, enabling functions such as confirmation reminders and cryopreservation storage when the donor donates again. Red blood cells of rare blood types are processed into frozen red blood cells for long-term storage. Results: Among voluntary blood donors, 16 cases of the ccDEE combined with Jk(a-) phenotype were identified (0.221 7%, 16/7 216); 10 cases of the ccDEE combined with Jk(b-) phenotype (0.138 6%, 10/7 216); 78 cases of the Fy(a-) phenotype (0.169 5%, 78/46 012); 39 cases of the Lu(b-) phenotype (0.138 2%, 39/28 214); 31 cases of the s(-) phenotype (0.081 8%, 31/37 913); 22 cases of the Di(b-) phenotype (0.029 9%, 22/73 691); 30 cases of the Jk(a-b-) phenotype (0.010 1%, 30/298 250); and 1 case of the k(-) phenotype (0.001 3%, 1/77 382), which was further identified as KELnull phenotype (K0). No p phenotype donors were identified (0/88 528). A total of 228 units of frozen red blood cells were prepared. The screening results were compared and analyzed with rare blood type data from other regions. Conclusion: This study, through a combination of different screening methods, significantly improved the efficiency of rare blood type screening while remaining cost-effective. By conducting large-scale screening and performing data informatization processing, a database and physical repository of rare blood types in the Guangzhou region were successfully established. This provides a strong guarantee for the timely supply of blood to patients with difficult-to-match and rare blood types in the region, effectively enhances the level of transfusion safety in the region, and offers a practical paradigm for constructing a comprehensive blood transfusion support system.

Objectives: . The prognostic value of the pretreatment albumin-to-alkaline phosphatase ratio (AAPR) in head and neck cancer (HNC) remains uncertain. This meta-analysis aimed to evaluate the predictive role of AAPR for survival outcomes in patients with HNC. Methods: . A comprehensive search of the Cochrane Library, PubMed, and Embase databases was conducted to identify relevant studies published up to July 30, 2024. We included studies on AAPR and survival outcomes in HNC patients. Results: . Eight studies comprising 1,737 HNC patients were analyzed using random-effects models. Lower AAPR values were significantly correlated with worse overall survival (hazard ratio [HR], 2.08), progression-free survival (HR, 2.00), and disease-free survival (HR, 2.18). Sensitivity analyses confirmed the robustness of these results, with no significant publication bias detected. Conclusion . Our findings suggest that pretreatment AAPR could serve as a valuable and cost-effective prognostic indicator in HNC, potentially aiding clinicians in risk stratification and treatment decision-making. However, additional validation studies are warranted to confirm its clinical applicability.

Objective: To characterize the sequence polymorphism of HLA-A, -B, and -C loci in the northern Han Chinese population and to evaluate their selection signals and phylogenetic patterns based on long-read sequencing data. Methods: A total of 408 unrelated healthy blood donors were enrolled. Long-read sequencing of HLA-A, -B, and -C loci was performed using the PacBio Sequel II platform. The Ewens-Watterson neutrality test, sliding-window nucleotide diversity (π) and Tajima′s D analyses were conducted, together with genetic distance heatmaps, principal coordinates analysis (PCoA), and maximum likelihood phylogenetic analysis to assess polymorphism distribution, selection signals, and phylogenetic structure across the three loci. Results: The analyzed sequence lengths for the HLA-A, -B, and -C loci were 3 257 bp, 3 794 bp, and 3 831 bp, respectively; the numbers of locus-specific sequence types were 44, 82, and 56, with corresponding locus-specific sequence type diversities of 0.905 2, 0.964 9, and 0.939 8, respectively. The Ewens-Watterson test showed no significant deviation from neutrality (P>0.05). Sliding-window analysis revealed elevated π and Tajima′s D values in exons 2 and 3 as well as in certain intronic regions of HLA-A and HLA-B, whereas HLA-C exhibited relatively lower overall diversity. Genetic distance heatmaps, PCoA, and phylogenetic analysis consistently showed clear clustering in HLA-A and HLA-C, while HLA-B displayed the highest phylogenetic heterogeneity. Conclusion: HLA-A, -B, and -C gene sequences in the northern Chinese Han population exhibit high levels of polymorphism and marked regional heterogeneity. HLA-B shows greater diversity, stronger signals of selection, and more complex phylogenetic structure compared with HLA-A and HLA-C.

ObjectiveTo investigate whether modified Taohe Chengqitang （JTCT） treats liver fibrosis by inhibiting hepatic sinusoidal capillarization， and to verify whether its specific mechanism is related to the Homologous genes responsible for the notches along the edges of Drosophila wings（Notch） signaling pathway and endothelial nitric oxide synthase （eNOS） signaling pathway. MethodsFifty C57BL/6 mice were randomized into 5 groups： Control， model （5 mL·kg^-1·3 d^-1）， low-dose JTCT， medium-dose JTCT， and high-dose JTCT （JTCT-L，JTCT-M，JTCT-H）. Except the control group， the other groups were intraperitoneally injected with 20% carbon tetrachloride （CCl₄） olive oil solution every 3 days for 4 weeks to induce liver fibrosis. Meanwhile， JTCT-L， JTCT-M， and JTCT-H groups were administrated with JTCT by gavage at doses of 16.6， 33.3， and 66.6 g·kg^-1·d^-1， respectively， for 4 consecutive weeks （the control and model groups received equal volumes of normal saline by gavage）. Primary liver sinusoidal endothelial cells （LSECs） were isolated from rat livers through in situ perfusion of collagenase， Percoll density gradient centrifugation， and selective removal of Kupffer cells. After verification of cell phenotype， LSECs were used for experiments. For cells at the logarithmic growth phase， the small interfering RNA（siRNA） kit was used to knock down the expression of soluble guanylate cyclase （sGC） through transient transfection. Subsequently， the Notch agonist Jagged-1 was applied. Cell counting kit-8 （CCK-8） was used to examine the cytotoxicity of JTCT on LSECs. Real-time PCR and Western blot were employed to measure the expression of molecules in the Notch and eNOS signaling pathways at mRNA and protein levels， respectively. Intracellular Ca²⁺ was labeled with the fluorescent probe Fluo-4 acetoxymethyl ester（Fluo-4/AM）. ResultsThe animal experiment showed that compared with the control group， the model group exhibited hepatic steatosis， inflammatory cell infiltration， hepatocyte degeneration and necrosis， lobular structural disorder， and fibrous tissue hyperplasia in the mouse liver tissue， significantly elevated serum levels of hydroxyproline （Hyp）， alanine transaminase （ALT）， and aspartate transaminase （AST） （P<0.01）， significantly upregulated expression levels of Notch1， Hes family bHLH transcription factor 1（Hes1）， Cluster of Differentiation 31（CD31）， and von Willebrand factor（vWF） （P<0.01）， and significantly downregulated phosphorylate（p）-eNOS/eNOS ratio and sGC expression （P<0.01）. Compared with the model group， all the JTCT groups showed significantly reduced serum Hyp， ALT， and AST levels （P<0.01）， downregulated expression of Notch1， Hes1， CD31， and vWF （P<0.05， P<0.01）， and upregulated p-eNOS/eNOS ratio and sGC expression （P<0.05， P<0.01） in the liver tissue， with the JTCT-H group showing the most significant changes （P<0.01）. The cell experiment showed that compared with the LSEC-1day group， the LSEC-5day group exhibited significantly increased expression of Notch1， Hes1， CD31， and vWF （P<0.01）， significantly decreased p-eNOS/eNOS ratio and sGC expression （P<0.01）， and elevated intracellular Ca²⁺ concentration （P<0.01）. Compared with the LSEC-5day group， the JTCT group showed decreased expression of Notch1， Hes1， CD31， and vWF （P<0.01）， significantly increased p-eNOS/eNOS ratio （P<0.01）， and significantly reduced intracellular Ca²⁺ concentration （P<0.01）. No significant differences were observed in the expression of Notch1， Hes1， eNOS， p-eNOS， CD31， vWF， sGC， or intracellular Ca²⁺ concentration between the Jagged1 group and the Jagged1+JTCT group. Compared with the LSEC-5day group， the sGC knockout group （sGC-KO） showed significantly increased expression of CD31 and vWF （P<0.01）. There was no significant difference in CD31 or vWF expression between the sGC-KO group and the sGC-KO+JTCT group. ConclusionJTCT inhibits the activation of the Notch signaling pathway and restores the activity of the eNOS signaling pathway to suppress sinusoidal capillarization of LSECs， thereby treating liver fibrosis.

ObjectiveTo investigate the effect and mechanism of cordycepin in inhibiting fat infiltration after rotator cuff injuries in rats by regulating the Wnt/β-catenin signaling pathway， providing a theoretical basis for clinical treatment of rotator cuff injuries. MethodsFifty SPF-grade female SD rats were used in this study， with 10 randomly selected as the blank group. A rotator cuff injury repair model was established by supraspinatus tendon and suprascapular nerve compression. The successfully modeled rats were randomized into model and low-dose （20 mg·kg^-1）， medium-dose （40 mg·kg^-1）， and high-dose （80 mg·kg^-1） cordycepin groups. After 6 weeks of treatment， the gait analysis was performed to assess the limb function in rats. Oil red O staining and Masson staining were employed to observe pathological changes in the muscle tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the serum. Immunohistochemistry （IHC） was employed to detect the expression of peroxisome proliferator-activated receptor γ （PPARγ） and CCAAT/enhancer-binding protein α （C/EBPα）， which are markers of adipogenesis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of Wnt3a， Wnt10b， and β-catenin. ResultsCompared with the blank group， the model group showed decreases in stride length and paw print area （P<0.01）， an increase in ratio of wet muscle mass reduction and a decrease in muscle fiber cross-sectional area （P<0.05）， and decreased ratios of fat infiltration area and collagen fiber area （P<0.01）. Additionally， the model group showed elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， up-regulated protein levels of PPARγ and C/EBPα （P<0.01）， and down-regulated mRNA and protein levels of Wnt3a， Wnt10b， and β-catenin （P<0.05， P<0.01）. Compared with the model group， the low-， medium-， and high-dose cordycepin groups showed increases in stride length and paw print area （P<0.01）， a decrease in ratio of wet muscle mass reduction and an increase in muscle fiber cross-sectional area （P<0.05）， and increases in ratios of fat infiltration area and collagen fiber area （P<0.05， P<0.01）. In addition， cordycepin lowered the serum levels of IL-1β， IL-6， and TNF-α （P<0.05， P<0.01）， down-regulated the protein levels of PPARγ and C/EBPα （P<0.01）， and up-regulated the mRNA and protein levels of Wnt3a， Wnt10b， and β-catenin （P<0.05， P<0.01）. ConclusionCordycepin can improve the limb function， alleviate rotator cuff muscle atrophy， fat infiltration， and fibrosis， and inhibit inflammation in rats by regulating the Wnt/β-catenin signaling pathway.

OBJECTIVE: To explore the clinical significance of preoperative neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and C-reactive protein (CRP) to albumin (ALB) ratio in spinal surgery patients with postoperative incision infection. METHODS: A total of 373 patients who underwent spinal surgery were collected and devided into two groups according to the postoperative incision infection situation. Among them, 65 cases in the incision infection group included 34 males and 31 females with a mean age of (56.01±9.78) years old;308 cases in the non incision infection group included 157 males and 151 females with a mean age of (55.54±10.19) years old. Blood cell analyzer was applied to detect neutrophils, lymphocytes, and platelets, and calculate NLR and PLR;immunoturbidimetry was applied to measure serum CRP and ALB levels and calculate CRP/ALB ratio;receiver operating characteristic (ROC) curve was applied to analyze the predictive value of preoperative NLR, PLR, and CRP/ALB ratio for postoperative spinal incision infection;Logistic multivariate regression was applied to analyze the influencing factors of incision infection after spinal surgery. RESULTS: The NLR(4.92±1.13), PLR (119.32±22.74), CRP/ALB ratio (10.19±2.51), operation time (3.02±0.64) h, history of diabetes 38.46%(25/65), and the proportion of patients with implant 32.31%(21/65) in the incision infection group were higher than those in the non incision infection group 3.72±0.81, 90.58±20.16, 7.23±2.21, (2.26±0.51) h, 16.88%(53/308), 11.69%(36/308), there were statistical differences(P<0.05). The AUC of preoperative NLR, PLR, and CRP/ALB ratio alone and in combination for predicting postoperative incision infection after spinal surgery was 0.786, 0.806, 0.839, and 0.926, respectively. Preoperative NLR, PLR, and CRP/ALB ratio were independent risk factors for postoperative incision infection in spinal surgery(P<0.05). CONCLUSION The determination of preoperative NLR, PLR, and CRP/ALB ratio is beneficial for early prediction of postoperative spinal incision infection, and the combined detection of the three can further improve the accuracy of the prediction results.
Humans ; Male ; Female ; Middle Aged ; Aged ; C-Reactive Protein/metabolism* ; Surgical Wound Infection/etiology* ; Adult ; Spine/surgery* ; Inflammation ; Preoperative Period

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.