OBJECTIVE To explore the improvine mechanism of Yifei xuanfei jiangzhuo formula （YFXF） on vascular dementia （VAD） model rats based on the growth factor receptor-bound protein 2 （GRB2）/extracellular signal-regulated kinase （ERK）/cardiolipin synthase 1 （CRLS1） pathway. METHODS VAD rat model was established by permanent bilateral common carotid artery ligation. Forty-eight successfully modeled rats were randomly divided into the model group （normal saline）， donepezil hydrochloride group （positive control group， 0.2 g/kg）， and YFXF low- and high-dose groups （12.18 and 24.36 g/kg， calculated based on the total amount of crude drug）， respectively. In addition， a sham operation group （normal saline） was set up. There were 12 rats in each group. Daily intragastric administration of drug or normal saline was performed for 30 consecutive days. After the last administration， the spatial cognitive ability of the rats was evaluated， the pathological morphology of the hippocampus was observed， the contents of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） in serum were detected， the expression levels of GRB2/ERK/CRLS1 pathway-related proteins and the mRNA levels of GRB2， CRLS1， NADH dehydrogenase subunit 1（ND1）， Tafazzin （TAZ）， phospholipid scramblase 3（PLSCR3） and the ATP content in hippocampal tissue were measured. RESULTS Compared with the sham operation group， the escape latency of rats in the model group was significantly prolonged （ P ＜0.05）， and the number of crossing platform was significantly reduced （ P ＜0.05）， while the number of pyramidal cells and Nissl bodies in the hippocampus decreased sharply； the content of TNF-α in serum was significantly increased （ P ＜0.05）， and the content of IL-4 was significantly decreased （ P ＜0.05）； the expression levels of GRB2 and CRLS1 proteins， the phosphorylation level of ERK protein， the relative expression levels of GRB2， CRLS1，ND1， TAZ， and PLSCR3 mRNA， and the content of ATP in hippocampal tissue were significantly decreased （ P ＜0.05）. Compared with the model group， the above pathological changes in the hippocampal tissue of each administration group were alleviated， and the quantitative indicators were significantly restored （ P ＜0.05）. CONCLUSIONS YFXF may improve hippocampal neuron injury in VAD rats by activating the GRB2/ERK/CRLS1 pathway, maintaining cardiolipin homeostasis， and improving mitochondrial energy metabolism.

ObjectiveTo investigate the mechanism by which adrenoceptor alpha 2A (Adra2a) regulates lipopolysaccharide (LPS)-induced inflammation in primary hepatocytes from lipopolysaccharide-binding protein (LBP) knockout mice (Lbp^-/-). MethodsPrimary hepatocytes from C57BL/6J and Lbp^-/- mice were isolated using a two-step perfusion method. An in vitro inflammatory model was established by LPS stimulation, and an in vivo inflammatory mouse model was established by intraperitoneal injection of LPS. The in vitro experiments were grouped as follows: Control group, LPS group, BRL+LPS group, OE-NC+LPS group, and OE-Adra2a+LPS group. The Control group served as the blank control. The LPS group involved stimulating primary hepatocytes with LPS. The BRL+LPS group involved pretreating primary hepatocytes with BRL-44408 maleate followed by LPS stimulation. The OE-NC+LPS group involved transfecting primary hepatocytes with an empty vector followed by LPS stimulation. The OE-Adra2a+LPS group involved transfecting primary hepatocytes with a lentivirus overexpressing Adra2a, followed by LPS stimulation. The in vivo experimental groups were divided into Control', LPS', BRL+LPS', OE-NC+LPS', and OE-Adra2a+LPS' groups. The Control' group served as the blank control. The LPS' group received intraperitoneal injection of LPS. The BRL+LPS' group received intraperitoneal injection of BRL-44408 maleate for pretreatment, followed by LPS injection. The OE-NC+LPS' group received intraperitoneal injection of empty vector for pretreatment, followed by LPS injection. The OE-Adra2a+LPS' group received intraperitoneal injection of a lentivirus overexpressing Adra2a for pretreatment, followed by LPS injection. Cell viability after Adra2a inhibition and overexpression was assessed via the Cell Counting Kit-8 (CCK-8) assay. RT-qPCR measured changes in gene expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) after Adra2a inhibition and overexpression. Western blotting was performed to detect Adra2a protein expression and phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase (JNK) following LPS stimulation. ResultsIn vitro experiments revealed that LPS stimulation significantly decreased Adra2a protein expression in primary hepatocytes from C57BL/6J mice compared to the Control group (P<0.05), whereas it increased in primary hepatocytes from Lbp^-/- mice (P<0.001). Compared to the LPS group, the BRL+LPS group exhibited significantly increased cell viability (P<0.01), reduced TNF-α, IL-6, and IL-1β gene transcription levels (P<0.01, P<0.001, P<0.001), and decreased phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.01, P<0.001, P<0.001). Compared with the OE-NC+LPS group, the OE-Adra2a+LPS group showed significantly decreased cell viability (P<0.001), increased gene transcription levels of TNF-α, IL-6, and IL-1β genes (P<0.001, P<0.01, P<0.001), and elevated phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.001). In vivo experiments showed that, compared with the LPS' group, the BRL+LPS' group exhibited significantly reduced phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.01). In the OE-Adra2a+LPS' group, the phosphorylation levels of ERK1/2, p38, and JNK were significantly elevated compared to the OE-NC+LPS' group (P<0.01, P<0.001, P<0.01). ConclusionLPS stimulation can cause a significant increase in Adra2a protein expression in primary hepatocytes of Lbp^-/- mice. Adra2a protein can regulate the level of LPS-induced inflammation in primary hepatocytes of Lbp^-/- mice through the MAPK signaling pathway.

OBJECTIVE: To summarize the clinical and genetic characteristics of children with Silver-Russell syndrome (SRS) and improve the recognition of this disease. METHODS: A retrospective analysis was conducted on the clinical manifestations and genetic testing results of 29 children with SRS diagnosed at the Children's Hospital Affiliated to Zhengzhou University between March 2016 and June 2025. RESULTS: The 29 children had included 18 boys and 11 girls, with the age ranging from 2 months to 16 years. Their primary clinical manifestations included postnatal growth retardation (100%), small for gestational age (SGA) (100%), characteristic facial features (90%), limb asymmetry (83%), feeding difficulties (76%), ulnar deviation of the fifth finger (69%), body mass index (BMI) of < -2 SD (62%), and abnormal bone age (55%), including 15 cases with delayed bone age for an average of 1.5 years and 1 case with advanced bone age for 2.5 years. Additional manifestations included abnormal sexual development in 11 cases (38%), dental malocclusion in 11 cases (38%), allergic diseases in 10 cases (34%), cardiac diseases in 9 cases (31%), skeletal abnormalities in 7 cases (24%), renal hypoplasia in 5 cases (17%), and abnormal cranial MRI findings in 5 cases (17%). Twenty children were treated with recombinant human growth hormone (rhGH) at a dose of 0.1 ~ 0.15 U/(kg.d). Among them, 7 cases achieved annual height increase of ≥ 10 cm, 11 cases achieved annual height increase of ≥ 5 ~ 9 cm, and 2 cases achieved annual height increase < 5 cm. Twenty three children exhibited hypomethylation of imprinted genes in the chromosome region of 11p15, 4 presented maternal uniparental disomy of chromosome 7 [UPD(7)mat], and 2 had harbored nonsense variants of the HMGA2 gene. CONCLUSION SRS patients may present with diverse clinical manifestations including postnatal growth retardation, SGA, characteristic facial features, limb asymmetry, feeding difficulties, and ulnar deviation of the fifth finger. Most patients may exhibit abnormal methylation in the 11p15 region. rhGH therapy can improve the height of these patients.
Humans ; Silver-Russell Syndrome/diagnosis* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Retrospective Studies

BACKGROUND:With changing lifestyles and aging,sagittal spinal imbalance has become a common orthopedic issue significantly affecting knee and pelvic function.Understanding the impact of sagittal spinal imbalance and its compensatory mechanisms is crucial for improving the clinical management of chronic pain.OBJECTIVE:To evaluate the alignment of the spine-pelvis-lower extremities using whole-body EOS imaging,analyze the correlation between spinal sagittal imbalance and knee joint parameters,and explore their compensatory mechanisms.METHODS:A total of 71 patients with chronic low back pain or patellofemoral pain who visited Department of Orthopedics,First Affiliated Hospital of Soochow University between January 1,2021 and December 31,2023 were included.Radiographic measurements were performed using whole-body EOS to determine pelvic tilt,pelvic incidence,lumbar lordosis,sagittal vertical axis,global tilt,hip-knee-angle,knee flexion angle,lateral distal femoral angle,and medial proximal tibial angle.Patients were classified into normal group(pelvic incidence-lumbar lordosis＜10°),compensated group(10°＜pelvic incidence-lumbar lordosis＜20°),and decompensated group(pelvic incidence-lumbar lordosis＞20°)based on the SRS-Schwab spinal deformity classification according to pelvic incidence-lumbar lordosis difference.The differences in radiographic parameters among the groups were analyzed.The differences in American Knee Society Knee Score and Oswestry Disability Index scores were compared among each group.Patients were divided into chronic low back pain group and non-chronic low back pain group,patellofemoral pain group and non-patellofemoral pain group based on clinical symptoms,and the relationship between radiographic parameter differences and clinical symptoms was analyzed.RESULTS AND CONCLUSION:(1)When pelvic incidence-lumbar lordosis was less than 20°,lateral distal femoral angle and medial proximal tibial angle tended to stabilize.When pelvic incidence-lumbar lordosis was greater than 20°,it showed a linear correlation with lateral distal femoral angle and medial proximal tibial angle,with lateral distal femoral angle increasing and medial proximal tibial angle decreasing with increasing pelvic incidence-lumbar lordosis values.(2)Compared with the normal group,the compensated group had significantly increased pelvic tilt(P＜0.01),while knee joint parameters hip-knee-angle and knee flexion angle showed no significant differences;the decompensated group showed significant increases in pelvic tilt(P＜0.01),and decreases in hip-knee-angle,and knee flexion angle(P＜0.01).Compared with the compensated group,the decompensated group showed a significant decrease in hip-knee-angle(P＜0.05),but had no significant differences in pelvic tilt and knee flexion angle.(3)Compared with the non-patellofemoral pain group,patients with patellofemoral pain had significant decreases in spinal lumbar lordosis,lateral distal femoral angle,and medial proximal tibial angle(P＜0.05)and a significant increase in pelvic incidence-lumbar lordosis(P＜0.05).(4)Patients with low back pain had significant differences in radiographic parameters compared with the non-chronic low back pain group(P＜0.05).(5)Compared with the normal group,both the compensated and decompensated groups showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P＜0.05).Compared with the compensated group,the decompensated group showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P＜0.05).(6)Pelvic incidence-lumbar lordosis values increased with age and were higher in females compared with males.(7)This study systematically reveals the spine and lower limbs play an important role in disease progression and clinical symptoms.Associated symptoms low back pain and patellofemoral pain are related to the stability of the spine-pelvis-lower extremity alignment.Furthermore,spinal sagittal imbalance is more severe in elderly and female patients.

BACKGROUND:Peripheral nerve axon rupture seriously affects patients' physical function and mental health.Microsurgery,nerve autograft,nerve allograft,fibrin glue and catheter technology are the main treatments for peripheral nerve injury,each of which has its own advantages and disadvantages,but the overall treatment effect is not satisfactory.Despite the clinical success of Schwann cells in promoting axonal regeneration,there are still many challenges in the treatment with Schwann cells,such as slow expansion of Schwann cells,immune rejection,and low survival rate of transplanted cells.OBJECTIVE:To summarize the role and mechanism of Schwann cells in promoting the regeneration of peripheral nerve axons,and the difficulties and challenges of Schwann cells in the process of nerve regeneration treatment.METHODS:PubMed,Medline,WanFang,VIP,and CNKI were searched by computer using the search terms of"Schwann cells,synaptic Schwann cell,macrophage,peripheral nerve axon rupture,Wallerian degeneration,Peripheral nerve axon regeneration,Central nervous system repair"in English and Chinese.Literature related to Schwann cell proliferation and differentiation,promotion of peripheral nerve regeneration,and clinical applications was retrieved from database inception to October 2024,and a total of 95 articles were finally included for review.RESULTS AND CONCLUSION:Schwann cells interact with macrophages,T cells and other cells,to initiate the regeneration process through signaling pathways,including Krox20/C-Jun,NRG-1/ErbB,Notch,MAPK,and PI3K/Akt/mTOR,synthesize and release nerve growth factors,and thus promote regeneration of the peripheral nervous system.Schwann cells have been experimentally demonstrated to have great potential in peripheral nerve repair and are expected to become the key target of therapeutic intervention.However,there are still problems such as difficulties in cell harvest and culture,as well as the occurrence of other diseases during the treatment process.

The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

Obesity， a global chronic disease， is associated with adipose tissue dysfunction， which is one of the contributing factors to obesity. The cyclic adenosine monophosphate （cAMP） signaling pathway， a key regulator of lipid metabolism， plays a pivotal role in obesity development. Various of traditional Chinese medicine monomers， such as flavonoids， lignans， phenols， and terpenoids， as well as traditional Chinese medicine compound formulas like Xiaoyao powder， Shengmai powder， and Zexie decoction， can maintain energy homeostasis， balance adipose tissue function， regulate glucose metabolism， improve insulin resistance， and suppress inflammatory responses through cAMP signaling pathway regulation， thereby intervening in lipid metabolism for obesity treatment. Although a substantial amount of basic research has preliminarily elucidated the potential mechanisms by which traditional Chinese medicine intervenes in obesity through the cAMP signaling pathway， clinical translational research remains inadequate. There is an urgent need for large-sample， high-quality randomized controlled trials to validate these findings.

Objective: Blood safety surveillance is a critical measure for the objective assessment of blood quality and enhancing transfusion safety. This study aims to comprehensively understand the current status of blood safety surveillance and management in blood collection and supply institutions in Sichuan Province, systematically analyze existing problems and vulnerabilities, and provide a basis for optimizing management strategies and improving capabilities to ensure blood safety. Methods: The Blood Safety Surveillance questionnaire was designed, covering adverse donor reaction reporting, management of adverse events, and transfusion adverse reaction feedback. An online survey was conducted via Questionnaire Star platform among 21 blood collection and supply institutions in the province, gathering information on management systems, process implementation, and utilization of monitoring data. The collected data were organized and statistically analyzed using Excel. Results: The questionnaire response rate and validity rate were both 100%. Blood collection and supply institutions in Sichuan Province have generally established a blood safety surveillance system and achieved positive outcomes. Regarding adverse events in blood collection and supply, 95.24% (20 institutions) have established reporting procedures, and 66.67% (14) collect information through multiple channels such as internal reports, external reports, and statistical trend feedback. A total of 90.48% (19) institutions regularly summarize and analyze adverse event data, and 85.71% (18) produce reports with improvement recommendations based on this analysis.71.43% (15) institutions implement reward and penalty measures, and 71.43% (15) report underreporting or omission due to accountability or performance concerns. In terms of monitoring adverse blood donation reactions, all blood collection and supply institutions have established full-process management systems.76.19% (16) collect data through multiple approaches, including on-site donation records, voluntary donor reports, and donor follow-ups. Adverse reactions were followed up in 95.24% (20) of institutions with 65% (13) completing follow-ups within 24 hours.80.95% (17) have established investigation procedures, while 66.67% (14) believe underreporting or omission still occurs. All blood collection and supply institutions regularly compile statistics on adverse donation reactions. Of these, 85.71% (18) institutions providing feedback to management departments and 90.48% (19) analyzing the data and making recommendations.76.19% (16) institutions use monitoring data for return donor management and targeted care, and 71.43% (15 stations) incorporate it into management reviews. Regarding adverse transfusion reactions, 95.24% (20) institutions have established and implemented procedures for isolating, recalling, and tracing of problematic blood units. However, only 42.86% (9) have established feedback mechanisms of adverse transfusion reaction with hospitals, and only 19.05% (4) support direct reporting via information systems.47.62% (10) institutions regularly analyze adverse transfusion reaction data, and 19.05% (4) provide feedback and recommendations to relevant hospitals. All blood collection and supply institutions reported challenges in collecting hospital feedback, citing complexities in data collection and reporting processes. Conclusion: Blood safety surveillance systems have been preliminarily established in Sichuan Province. However, further strengthening is still required, including conducting in-depth data analysis and utilization, standardizing the configuration of emergency medications and equipment, and improving feedback mechanisms for adverse transfusion reactions. To improve the overall level of blood safety management, it is recommended to strengthen closed-loop data management, improve feedback mechanisms between blood collection and supply institutions and hospitals, foster a non-punitive reporting culture, and systematically advance the regionalization and standardization of the monitoring system. These efforts will contribute to sustainably improving the overall effectiveness and sustainability of blood safety management.

AIM:To investigate the effect of ranibizumab on blood flow density in different regions of the macula in patients with macular edema(ME)secondary to ischemic and non-ischemic branch retinal vein occlusion(BRVO).METHODS:This retrospective study enrolled patients with BRVO-ME who were treated at the hospital from September 2019 to March 2021. Patients were divided into ischemic and non-ischemic groups based on fundus findings. All patients received intravitreal injections of ranibizumab once monthly for three consecutive months. Best corrected visual acuity(BCVA), central macular thickness(CMT), and macular blood flow density were measured before treatment and at 1 d, 1 wk, 1 and 3 mo after treatment.RESULTS: A total of 46 patients(46 eyes)with BRVO-ME were included, comprising 21 eyes in the ischemic group(7 males, 14 females; mean age 55.81±10.36 y)and 25 eyes in the non-ischemic group(11 males, 14 females; mean age 54.84±9.81 y). At 3 mo after treatment, BCVA(LogMAR)in the non-ischemic group was superior to that in the ischemic group(0.19±0.19 vs 0.38±0.27, P=0.009). Analysis of CMT changes showed that the reduction amplitude in the ischemic group was significantly greater than that in the non-ischemic group at both 1 and 3 mo after treatment(all P<0.05). Blood flow densities in the whole, parafoveal, and perifoveal regions of the superficial capillary plexus(SCP), as well as in the whole and perifoveal regions of the deep capillary plexus(DCP), were significantly lower in ischemic patients than in non-ischemic patients, while blood flow density in the foveal region of DCP was significantly higher in the ischemic group(all P<0.05).CONCLUSION: Ranibizumab is effective for both types of patients. Non-ischemic patients have a better long-term visual prognosis, and the advantage may be related to better blood flow perfusion patterns in specific areas 3 mo after treatment. Monitoring changes in blood flow density in these areas can help provide personalized treatment for patients.