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.

Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

ObjectiveTo explore the potential mechanism underlying electroacupuncture therapy with the midnight-noon ebb-low method with hour-prescription for chronic obstructive pulmonary disease （COPD） with lung-qi deficiency syndrome from the perspective of brain and muscle basic helix-loop-helix ARNT-like 1 （BMAL1） as well as neutrophil extracellular traps （NETs）. MethodsThe experiment was conducted in two phases. For the therapeutic effectiveness observation， 24 rats were randomly allocated into control group 1， model group 1， midnight-noon electro-acupuncture group 1 and conventional electro-acupuncture group， with 6 rats per group. Rat models of COPD with lung-qi deficiency syndrome were established via cigarette smoke exposure combined with intratracheal instillation of lipopolysaccharide （LPS）. After successful modelling， rats in midnight-noon electro-acupuncture group 1 received electro-acupuncture at acupoints "Taiyuan （LU 9）"， "Feishu （BL 13）" and "Zusanli （ST 36）" during 05：00—07：00， 30 minutes per treatment once every other day for 14 consecutive days （7 sessions in total）. Rats in the conventional electro-acupuncture group received identical electroacupuncture manipulation at random daytime hours （08：00—18：00）. Pulmonary function parameters including forced expiratory volume in 0.3 second （FEV_0.3）， forced vital capacity （FVC） and FEV_0.3/FVC ratio were detected. Pulmonary histopathological changes were observed via hematoxylin-eosin （HE） staining. Plasma levels of pro-inflammatory factors interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， as well as pulmonary reactive oxygen species （ROS） content， BMAL1 protein expression and the levels of neutrophil extracellular traps （NETs） biomarkers such as myeloperoxidase （MPO）， neutrophil elastase （NE）， and citrullinated histone H3 （CitH3） in lung tissue were determined. For the mechanistic verification phase， 36 rats were divided into control group 2， model group 2， midnight-noon electro-acupuncture group 2， overexpression empty group， overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group， with 6 rats in each group. At the 5th week of model construction， rats in the overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group received intratracheal instillation of 100 μl adenoviral suspension carrying overexpressed Bmal1 gene. Rats in the overexpression empty group were injected with an equal titer and equal volume of blank adenovirus without the Bmal1 coding sequence into the lung at the identical time point. Midnight-noon electro-acupuncture group 2 and overexpression with midnight-noon electro-acupuncture group were consistent with the aforementioned protocol. Finally， pulmonary levels of MPO， NE and CitH3 were measured in all groups. ResultsCompared with the control group 1， the model group 1 exhibited decreased FEV_0.3， FVC and FEV_0.3/FVC ratio， elevated plasma IL-1β， TNF-α and pulmonary ROS levels， downregulated lung BMAL1 protein expression， and increased contents of MPO， NE and CitH3 （all P＜0.05）； typical NETs-like structures with sparse granular substances attached to fibrous networks were observed under scanning electron microscopy； HE staining revealed damaged alveolar architecture accompanied by inflammatory cell infiltration. Compared with model group 1， both the midnight-noon electro-acupuncture group 1 and conventional electro-acupuncture group achieved obvious improvements in all above indicators， with superior therapeutic effects in midnight-noon electro-acupuncture group 1 （P＜0.05）. Consistently， midnight-noon electro-acupuncture group 1 showed more prominent alleviation of NETs-like structure formation and lung pathological injury compared to the conventional electro-acupuncture group. Mechanistic validation results demonstrated that compared with model group 2， the average optical density of MPO as well as the protein levels of MPO， NE and CitH3 were markedly reduced in midnight-noon electro-acupuncture group 2， overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group （P＜0.05）； furthermore， these parameters were significantly lower in the overexpression with midnight-noon electro-acupuncture group than in midnight-noon electro-acupuncture group 2 （P＜0.05）. ConclusionElectro-acupuncture based on the midnight-noon ebb-low method with hour-prescription may alleviate pulmonary inflammation in COPD by upregulating the expression of clock protein BMAL1 and inhibiting excessive accumulation of NETs in lung tissue.

Objective To analyze the overall characteristics, research hotspots, and development trends of immune cell-related studies in radiotherapy for rectal cancer. Methods A systematic search was conducted by using Web of Science Core Collection to retrieve articles related to radiation therapy and immune cells in rectal cancer published from 1991 to 2024. Advanced bibliometric tools, such as VOSviewer and CiteSpace, were utilized to facilitate analysis and describe publication trends, geographic contributions, institutional affiliations, journal prominence, author collaboration, and prominent keywords. Results The annual number of relevant publications has increased steadily, showing remarkable growth over the past five years. Studies focusing on adaptive immune cells (T and B cells) account for the largest proportion of works and form the most extensive collaboration networks, reflecting the central role of T cell–mediated antitumor immunity in radiotherapy. Meanwhile, innate immune cells, including myeloid-derived suppressor cells, macrophages, monocytes, and neutrophils, are increasingly investigated for their regulatory roles in shaping the tumor immune microenvironment and influencing therapeutic responses. Among countries, China and the United States have contributed the highest number of publications and demonstrated strong academic influence. While several stable research groups have been formed, intergroup collaboration remains limited. Keyword analysis revealed that radiotherapy-induced immune modulation, tumor immune microenvironment remodeling, and treatment response have emerged as major research hotspots. Conclusion Research on immune cells in rectal cancer radiotherapy has progressed rapidly in recent years. The emphasis of this field has gradually shifted from single-treatment approaches to mechanistic studies investigating the interaction between radiotherapy and the tumor immune microenvironment. The field still demonstrates considerable potential for future research and clinical translational applications.

AIM:To compare the clinical efficacy of defocus rigid gas permeable contact lenses(RGPCL)and highly aspherical lenslets(HAL)for myopia control in children and adolescents with moderate to high myopia.METHODS:A retrospective study was conducted, enrolling patients aged 8-17 y with moderate to high myopia who presented to Sichuan Eye Hospital, Aier Eye Hospital Group between January 2022 and January 2024. Subjects were divided into the RGPCL group and the HAL group according to myopia correction modalities. Refractive diopters, axial length, corneal curvature, and visual quality were examined at 6 and 12 mo after lens wear, and relevant data were statistically analyzed.RESULTS:A total of 96 eyes from 96 cases were enrolled, with 48 cases(48 eyes, 8 males and 40 females)allocated to the RGPCL group with a median age of 12.00(11.50, 15.00)y, and 48 cases(48 eyes, 14 males and 34 females)to the HAL group with a median age of 13.00(12.00,14.00)y. At the 6-month follow-up, no significant changes in spherical diopters were observed in either group relative to baseline. Spherical diopters increased in both groups at the 12-month visit, with a significantly smaller increment in the RGPCL group(P<0.01). At the 6- and 12-month follow-up visits, the magnitude of changes in cylindrical refractive power was markedly larger in the RGPCL group relative to the HAL group(P<0.01). At the 6-and 12-month follow-up visits, axial length in both groups had increased relative to baseline, and no significant intergroup difference was detected in axial elongation(P>0.05). At 6 and 12 mo of lens wear, no significant difference in K1,K2 was found in the HAL group compared with baseline, while the K2 value decreased significantly in the RGPCL group(P<0.0167). The RGPCL group achieved substantially higher scores in four domains including visual clarity, image scaling, glare tolerance, visual field range and total at both follow-up time points(all P<0.001).CONCLUSION:Defocus RGPCL yields superior performance in slowing the progression of spherical and cylindrical, as well as providing better overall visual experience, when compared with HAL.

ObjectiveTo systematically summarize the relevant pathophysiology underlying muscle fatigue in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). MethodsDatabases including PubMed, Web of Science Core Collection, Embase, Cochrane Library, EBSCO (CINAHL), CNKI, Wanfang Data and VIP Database were searched from their inception to July, 2025 for basic and clinical studies related to ME/CFS. Multidimensional evidence involving mitochondrial, neuromuscular junction dysfunction, autonomic dysregulation and immune-inflammatory responses was integrated. The role of muscles in the central-immune-metabolic-neural regulatory network and its association with clinical phenotypes were evaluated. ResultsPatients with ME/CFS commonly presented with impaired mitochondrial energy supply, oxidative stress, ion homeostasis disorders, reduced stability of neuromuscular junction transmission, insufficient central drive and postural intolerance. These abnormalities resulted in a predisposition to cross the anaerobic threshold and trigger post-exertional malaise. ConclusionMuscle pathophysiology plays a critical role in the pathogenesis and symptom persistence of ME/CFS. Rehabilitation practice should prioritize safety boundaries to avoid post-exertional malaise.

Objective: This study employed next-generation sequencing (NGS) for large-scale genotyping of 42 blood group systems in blood donors to evaluate its applicability in multi-system blood group identification and rare blood type repository construction, while exploring the complementary value of third-generation sequencing (TGS) in haplotype phasing and variant capture in regions with insufficient sequencing depth for ABO ambiguous samples. Methods: A total of 562 regular blood donors (median donation frequency 11 times) from a blood center were enrolled. NGS was used for genotyping of 42 blood group systems, with a focused analysis on 12 systems essential for rare blood type repository construction: MNS, Lutheran, Kell, Duffy, Kidd, Diego, Yt, Colton, Gerbich, Ok, H, and I. TGS was employed to resolve haplotype phasing (i. e., determining whether different mutation sites are located on the same chromosome) in 12 ABO samples with discrepancies between forward and reverse typing. Serological and genotyping results were compared for MNS, Duffy, Kidd, Lewis, and ABO systems. Results: NGS-based genotyping revealed that Fy (a-b+) in the Duffy system accounted for 0.87% (4/458), and Di (a+b+) in the Diego system accounted for 10.62% (31/292). The Lutheran, Kell, Yt, Colton, H, Ok, I, and Gerbich systems exhibited near-uniform phenotype distributions. Among the 12 ABO ambiguous samples, NGS yielded multiple possible genotype combinations in 5 cases due to inability to phase alleles, whereas TGS uniquely resolved the genotypes through long-read sequencing. In one case, NGS detected only 2 mutation sites due to insufficient sequencing depth, while TGS identified all 11 sites and assigned the A1 phenotype. Concordance rates between serology and genotyping were: Duffy 96.55% (140/145), ABO 96.43% (513/532), Kidd 94.17% (97/103), MNS 85.07% (57/67), and Lewis 68.18% (75/110). In the MNS system, 7 of 8 samples serologically typed as M+N+ but genotyped as M-N+ carried GYPB variants. Lewis discrepancies predominantly featured genotype Le (a-b+) with serological phenotypes of Le (a+b-), Le (a+b+), or Le (a-b-). The NGS platform completed sequencing of 192 samples within 2 weeks. Conclusion: The tiered genotyping strategy combining NGS, TGS, and serology enables multi-system blood group identification in large-scale blood donor populations. TGS provides complementary value in phasing ambiguous ABO samples and detecting variants in regions with insufficient sequencing depth. This study provides a technical framework and baseline frequency data for the expansion of a local rare blood type repository. However, standardization and cost-effectiveness of this strategy require further validation with expanded sample sizes, and serological confirmation should be retained for secretion status-related systems such as Lewis.

ObjectiveTo investigate the effect of icariin （ICA） on steroid-induced ferroptosis in bone microvascular endothelial cells （BMECs）. MethodsRat BMECs were selected and treated with 500 mg·L^-1 hydrocortisone for 1.5 h to establish a ferroptosis model of BMECs. The experimental cells were divided into a blank group， hormone group （500 mg·L^-1 hydrocortisone）， ICA group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA）， and ferroptosis agonist group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA + 2.7 mg·L^-1 erastin）. Cell viability was detected by CCK-8. The levels of ferrous ion， glutathione （GSH）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and reactive oxygen species （ROS） were detected by related kit species. The ferroptosis-related proteins， such as glutathione peroxidase 4（GPX4）， ferritin light chain （FTL）， and transferrin receptor protein1 （sTfR） were detected by Western blot， as well as autophagy-related proteins including microtubule-associated protein 1 light chain 3B （LC3B）， Beclin1， B-cell lymphoma-2 （Bcl-2）， and Caspase-3. Results500 mg·L^-1 hydrocortisone intervention for 1.5 h could effectively induce ferroptosis in BMECs， and ferroptosis levels could reach a peak as the intervention continued. In terms of cellular antioxidant capacity， compared with those in the blank group， the cell vitality， GSH in the hormone group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions were significantly increased （P<0.01）. Compared with those in the hormone group， the cell viability， GSH were significantly increased， and the levels of ROS， SOD， MDA， and ferrous ions were decreased in the ICA group （P<0.01）. Compared with those in the ICA group， the cell vitality， GSH in the ferroptosis agonist group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions increased significantly （P<0.01）. In terms of the relationship between ferroptosis and autophagy， compared with the blank group， the hormone group had significantly increased expression levels of LC3B， sTfR， Beclin1， and FTL and significantly decreased expression levels of GPX4 （P<0.01）. Compared with the hormone group， The ICA group had significantly decreased expression levels of LC3B， sTfR， and FTL and significantly increased expression levels of Beclin 1 and GPX4 （P<0.01）. Compared with those in the ICA group， the expression levels of LC3B， sTfR， and FTL increased in the rapamycin group， and those of Beclin 1 and GPX4 decreased （P<0.01）. In terms of cell ferroptosis and apoptosis，compared with the blank group， the hormone group had significantly increased expression levels of FTL， sTfR and Caspase-3 and significantly decreased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with the hormone group， the ICA group had significantly decreased expression levels of FTL， sTfR and Caspase-3 and significantly increased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with those in the ICA group， the expression levels of FTL， sTfR and Caspase-3 in the ferroptosis agonist group were increased， and the expression levels of GPX4， and Bcl-2 were decreased （P<0.01）. In terms of cell function，compared with that in the blank group， the ability of cell migration and tube formation was significantly decreased in the hormone group （P<0.01）. Compared with that in the hormone group， the cell migration and tube formation ability in the ICA group were significantly increased （P<0.01）. ConclusionFerroptosis is involved in steroid-induced damage in BMECs. ICA can inhibit steroid-induced ferroptosis in BMECs， and the mechanism may be associated with the inhibition of ferroptosis by regulating autophagy.

ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

OBJECTIVE: To compare the clinical efficacy of oblique lateral interbody fusion(OLIF) combined with lateral fixation and transforaminal lumbar interbody fusion(TLIF) in patients with lumbar spinal stenosis. METHODS: Totally 47 patients with lumbar stenosis from November 2018 to December 2021 were analyzed retrospectively and were divided into two groups according to the surgical methods. Among them, 21 cases underwent oblique lumbar interbody fusion supplemental anterolateral screw and rod instrumentation, including 5 males and 16 females, with a mean age of (68.19±6.13) years old ranging 55 to 74 years; the other 26 cases underwent posterior pedicle screw fixation and reduction were recorded, including 8 males and 18 females with a mean age of (65.35±7.64) years old ranging 54 to 78 years. Visual analogue scale(VAS) of pain was recorded to evaluate the degree of low back pain and lower extremity pain. The radiographic parameters were collected to evaluate the efficacy of two approaches including disc height, foraminal height, canal sagittal diameter and cross-sectional area. RESULTS: All operations were completed successfully. The wound healed normally and bone fusion was obtained in the last final follow up. No serious complication was occurred in both groups. One case of dural tear occurred in direct compression group. Four cases of left thigh weakness and pain were recorded in indirect decompression group. The average postoperative follow-up was(21.69±4.37)months in direct compression group, while(20.43±4.80)months in another group. There were no significant difference in bone density, body mass index(BMI), hospital stay, Cobb angel(P>0.05). The differences in intra-operative blood loss, operation time, disc height, foraminal height between two groups were statistically significant(P<0.05). The area and sagittal diameter of the spinal canal in the two groups were significantly improved after surgery(P<0.05). CONCLUSION Both two fusion methods have achieved good clinical results in the treatment of lumbar spinal stenosis, with the advantages of good stability, fast recovery and high fusion rate. Compared with TLIF, the advantage of OLIF has greater advantages in less bleeding and less trauma.
Humans ; Male ; Female ; Spinal Stenosis/surgery* ; Spinal Fusion/methods* ; Aged ; Middle Aged ; Lumbar Vertebrae/surgery* ; Retrospective Studies ; Treatment Outcome