Objective To investigate the role of activating transcription factor 4 (ATF4) in benign prostatic hyperplasia (BPH) in order to elucidate the molecular mechanism underlying BPH progression. Methods Firstly, we analyzed the correlation between the expression of ATF4 and the volume of prostate transition zone in BPH tissues using publicly available datasets. Subsequently, we explored the potential association among ATF4, epithelial-mesenchymal transition (EMT) and BPH through single-cell RNA sequencing (scRNA-seq). Finally, we validated the findings by silencing ATF4 and treating BPH cells with ATF4 protein inhibitors, followed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), CCK-8 assay, and Western blot. Results The expression of ATF4 in BPH tissues exhibited a significant positive correlation with the volume of prostate transition zone (r=0.64, P＜0.05). scRNA-seq analysis revealed that ATF4 was significantly upregulated in the prostate epithelial cells of BPH patients (P＜0.05), and its expression demonstrated a significant positive correlation with the Hallmark EMT singscore (r=0.14, P＜0.05). In vitro experiments further indicated that knockdown of ATF4 led to a significant reduction in the proliferative activity of BPH-1 cells (P＜0.05). Similarly, inhibition of ATF4 activity resulted in a marked decrease in the proliferative capacity and EMT of BPH-1 cells (P＜0.05). Conclusion ATF4 may exert a promoting effect on BPH by modulating the EMT signaling pathway;therefore, ATF4 may serve as a novel therapeutic target of BPH.

Fungal keratitis represents a significant cause of blindness, with current therapeutic approaches yielding limited success. The disease's onset and progression are primarily driven by fungal virulence factors and the host's immune response. The innate immune system is the first to respond, with neutrophils playing a pivotal role in the antifungal defense. Although neutrophils are critical for pathogen clearance, their excessive or abnormal activation can lead to tissue damage, exacerbating the disease. Thus, elucidating the mechanisms underlying neutrophil activity in fungal keratitis is crucial for refining treatment strategies. This article aims to systematically review the principal antimicrobial mechanisms employed by neutrophils, including phagocytosis, degranulation, and the formation of neutrophil extracellular traps(NETs). Furthermore, it explores the crosstalk between neutrophils and macrophages, alongside their collective impact and underlying mechanisms in the context of fungal keratitis. Exploration of the mechanisms of fungal keratitis facilitates precise intervention and enhances the efficacy of treatment.

Background: and Purpose Essential tremor with a midline distribution (Mid-ET) may represent a distinct subtype of essential tremor (ET) that primarily affects midline structures, often indicating advanced disease stage and increased severity. Recent studies have highlighted the complexity of Mid-ET, but research on neurological soft signs (NSS) in Mid-ET remains insufficient. Methods: The patients with ET included in this cross-sectional study were divided into two subgroups based on whether or not the ET had a midline distribution: Mid-ET and No-MidET. Comparative analyses were performed to assess clinical features and NSS prevalence in these subgroups. Results: Among 1,160 patients, 567 (48.9%) were Mid-ET and 593 (51.1%) were No-Mid-ET.The prevalence rates of head, face (including the jaw), and voice tremors were 31.9%, 23.0%, and 25.8%, respectively. In Mid-ET, tremor often affects multiple midline structures simultaneously. In the entire cohort, 24.7%, 16.6%, and 7.6% of patients exhibited tremors in one, two, and three midline structures, respectively. The prevalence of common NSS, including mild cognitive impairment, impaired tandem gait, and questionable dystonic posturing, was significantly higher in the Mid-ET than the No-Mid-ET subgroup (all p<0.001). Furthermore, we found that female sex (p<0.001), olfactory dysfunction (p=0.003), and questionable dystonic posturing (p=0.004) were associated with Mid-ET. Conclusions Mid-ET and No-Mid-ET presented significant clinical differences. The presence of questionable dystonic posturing may contribute to the distinct characteristics of Mid-ET, suggesting the presence of pathophysiological differences between the subgroups. Further investigations are warranted to determine the potential pathophysiological link between NSS and Mid-ET.

Background: and Purpose Essential tremor with a midline distribution (Mid-ET) may represent a distinct subtype of essential tremor (ET) that primarily affects midline structures, often indicating advanced disease stage and increased severity. Recent studies have highlighted the complexity of Mid-ET, but research on neurological soft signs (NSS) in Mid-ET remains insufficient. Methods: The patients with ET included in this cross-sectional study were divided into two subgroups based on whether or not the ET had a midline distribution: Mid-ET and No-MidET. Comparative analyses were performed to assess clinical features and NSS prevalence in these subgroups. Results: Among 1,160 patients, 567 (48.9%) were Mid-ET and 593 (51.1%) were No-Mid-ET.The prevalence rates of head, face (including the jaw), and voice tremors were 31.9%, 23.0%, and 25.8%, respectively. In Mid-ET, tremor often affects multiple midline structures simultaneously. In the entire cohort, 24.7%, 16.6%, and 7.6% of patients exhibited tremors in one, two, and three midline structures, respectively. The prevalence of common NSS, including mild cognitive impairment, impaired tandem gait, and questionable dystonic posturing, was significantly higher in the Mid-ET than the No-Mid-ET subgroup (all p<0.001). Furthermore, we found that female sex (p<0.001), olfactory dysfunction (p=0.003), and questionable dystonic posturing (p=0.004) were associated with Mid-ET. Conclusions Mid-ET and No-Mid-ET presented significant clinical differences. The presence of questionable dystonic posturing may contribute to the distinct characteristics of Mid-ET, suggesting the presence of pathophysiological differences between the subgroups. Further investigations are warranted to determine the potential pathophysiological link between NSS and Mid-ET.

Background: and Purpose Essential tremor with a midline distribution (Mid-ET) may represent a distinct subtype of essential tremor (ET) that primarily affects midline structures, often indicating advanced disease stage and increased severity. Recent studies have highlighted the complexity of Mid-ET, but research on neurological soft signs (NSS) in Mid-ET remains insufficient. Methods: The patients with ET included in this cross-sectional study were divided into two subgroups based on whether or not the ET had a midline distribution: Mid-ET and No-MidET. Comparative analyses were performed to assess clinical features and NSS prevalence in these subgroups. Results: Among 1,160 patients, 567 (48.9%) were Mid-ET and 593 (51.1%) were No-Mid-ET.The prevalence rates of head, face (including the jaw), and voice tremors were 31.9%, 23.0%, and 25.8%, respectively. In Mid-ET, tremor often affects multiple midline structures simultaneously. In the entire cohort, 24.7%, 16.6%, and 7.6% of patients exhibited tremors in one, two, and three midline structures, respectively. The prevalence of common NSS, including mild cognitive impairment, impaired tandem gait, and questionable dystonic posturing, was significantly higher in the Mid-ET than the No-Mid-ET subgroup (all p<0.001). Furthermore, we found that female sex (p<0.001), olfactory dysfunction (p=0.003), and questionable dystonic posturing (p=0.004) were associated with Mid-ET. Conclusions Mid-ET and No-Mid-ET presented significant clinical differences. The presence of questionable dystonic posturing may contribute to the distinct characteristics of Mid-ET, suggesting the presence of pathophysiological differences between the subgroups. Further investigations are warranted to determine the potential pathophysiological link between NSS and Mid-ET.

Xiao Chaihutang， originating from the Treatise on Typhoid and Miscellaneous Diseases， is a classic formula for harmonizing the Shaoyang. It excels in regulating the pivotal mechanism and unblocking the triple energizer， corresponding to the pathogenesis of digestive system tumors characterized by the interlocking of deficiency， stasis， phlegm， and toxicity， as well as disharmony between Yin and Yang. This paper systematically reviews research findings from China and abroad over the past decade， exploring the anti-tumor effects of Xiao Chaihutang on digestive system tumors from three dimensions： theoretical rationale， clinical efficacy， and molecular mechanisms. At the level of principle and method， Xiao Chaihutang takes "harmonization" as its core therapeutic guideline. By reconciling the exterior and interior to restore the Shaoyang pivot， harmonizing Yin and Yang to improve the tumor microenvironment， and regulating the liver and spleen to consolidate and protect the foundation of postnatal essence， it promotes the restoration of the body's dynamic balance of Yin and Yang. Clinical studies have demonstrated that Xiao Chaihutang， used alone or in combination with modern medical therapies， shows definite efficacy against digestive system tumors such as hepatocellular carcinoma， pancreatic carcinoma， and gastrointestinal carcinoma. It can significantly improve patients' quality of life， inhibit tumor progression， effectively relieve concomitant symptoms such a s cancer-related fever， anxiety， depression， and insomnia， and alleviate postoperative embolic syndromes as well as adverse reactions to radiotherapy and chemotherapy. Experimental studies have revealed that Xiao Chaihutang can inhibit tumor cell proliferation， induce apoptosis， arrest the cell cycle， suppress tumor cell invasion and metastasis， and improve the tumor microenvironment. Through the above analysis， this study elucidates the current clinical and experimental research status of Xiao Chaihutang in the treatment of digestive system tumors， aiming to provide theoretical support for its precise clinical application. On this basis， it further explores key issues in the identification of pharmacodynamic substances and the accumulation of evidence in evidence-based medicine， thereby offering a new perspective for the innovative development of integrative Chinese and Western medicine in synergistic cancer therapy.

Objective:To investigate the effect of extracorporeal membrane oxygenation (ECMO) in assisting neonates with complex congenital heart diseases (CHD) and the survival rate of the patients.Methods:A retrospective case-control study was made on 22 newborns with complex CHD assisted by ECMO during the perioperative period in Fuwai Central China Cardiovascular Hospital from January 2018 to June 2024.There were 19 males and 3 females in the newborns included, with an average age of (10.4±8.7) days (range: 1-26 days) and an average weight of (3.1±0.3) kg.Complex CHD included total anomalous pulmonary venous connection in 9 cases (40.9%), interrupted aortic arch and coarctation in 8 cases (36.4%), transposition of great arteries in 3 cases (13.6%), double outlet right ventricle in 1 case (4.5%) and cardiac tumor in 1 case (4.5%).The patients were divided into the <5 d group, 5-12 d group, and >12 d group according to the duration of ECMO support.Data were compared using the t-test or χ2 test. Results:There were 8 cases (36.4%) successfully weaned from ECMO support and 6 cases (27.3%) survived.ECMO support was used routinely in 15 cases (68.2%), and for extracorporeal cardiopulmonary resuscitation in 7 cases (31.8%).The duration of ECMO support was (5.9±3.7) days.There were no statistically differences in age, weight, gender, disease composition, operation time, cardiopulmonary bypass time, cross-clamp time, assistant time, blood routine, liver and kidney function and other biochemical indicators, preoperative cardiac ejection fraction value, procalcitonin, C-reactive protein and other infection indicators between the death group and the survival group (all P>0.05).The highest lactate values 24 hours before [(8.1±5.4) mmol/L] and after ECMO support [(10.5±7.1) mmol/L] in the survival group were significantly lower than those in the death group [(18.7±9.2) mmol/L, (21.3±8.6) mmol/L] ( t=2.606, P=0.018; t=2.729, P=0.013).It was found that the survival rate was 0/9 (0) in the <5 d group, 6/12 (50.0%) in the 5-12 d group, and 0/1 (0) in the >12 d group.The survival rate of the 5-12 d group was the highest, which was significantly higher than that of the <5 d group ( χ2=6.300, P=0.012). Conclusions:ECMO support is an effective treatment for severe circulatory failure in neonates with complex CHD in the perioperative period.The highest lactate levels 24 hours before and after ECMO support affect the survival rate.Patients receiving 5-12 d ECMO support can achieve the highest survival rate.

Objective To investigate the distribution of A subgroups in the A and AB blood type populations among voluntary blood donors in Zhongshan,study the antigen-antibody characteristics of A subgroups,establish a local A subgroup database,and support the development of precision medicine.Methods ABO subgroup screening was performed using the microplate method.Specimens negative for monoclonal anti-A1 reactivity underwent sequencing of exons 1～7 of the ABO gene to confirm genotypes.Cryopreservation and thawing of glycerolized subgroup red blood cells(RBCs),as well as preservation efficacy of concentrated human-derived antibodies with preservatives,were studied.Results Among 1 212 blood donor specimens,28 subgroup specimens were identified,with a prevalence of 1.54%(15/971)in blood type A and 5.39%(13/241)in blood type AB.Sequencing of 10 specimens revealed 7 ABO genotypes:ABO*A2.01/O.01.02(2 cases),ABO*A1.02/B.01(3 cases),ABO*BA.02/O.01.02,ABO*AW.31.02-05/A2.05,ABO*A2.05/B.01,ABO*A2new/O.01.01,and ABO*A1.02/O.01.01(1 case each).Additionally,one rare allele mutation(c.700C>G)and one novel allele mutation(c.203G>T)(GenBank accession number:PQ152337)were identified.Human anti-A1 antibodies with a titer of 8 were successfully concentrated.Optimal preservation conditions included 0.1%preservative concentration and cryopreserved subgroup RBCs stored at 4℃for 3 days post-thaw.Conclusion The predominant A subgroups in Zhongshan donors are A2 and B(A).A preliminary database for A2 and A2B subgroups is established,along with the discovery of a novel ABO allele mutation.Cryopreservation with glycerol,PEG antibody concentration,and ProClin 300 preservative demonstrate effective applications in preserving ABO blood group antigens and antibodies.

Essential tremor (ET) is one of the most common movement disorders, and its main clinical feature is action tremor at 4-12 Hz in both upper limbs. With the development and progress of disease, the cognition of ET has changed from benign, single-symptomatic and age-related disease to the disease with heterogeneity in etiology, pathology and clinical manifestation. At present, the etiology and pathogenesis of ET have not been fully defined. With the development of technology, magnetic resonance imaging has been widely used in the research of ET due to its advantages of high temporal and spatial resolution, multi-angle, multi-parameter imaging, and no ionizing radiation, and many new discoveries have been made in the neuropathophysiological mechanism. In this regard, this paper summarizes the latest progress of magnetic resonance imaging in ET, including structural magnetic resonance imaging, functional magnetic resonance imaging, etc., for the purpose of exploring the pathophysiology of ET and looking forward to clinical application prospects of magnetic resonance imaging.

Objective:To report a case of spastic paraplegia type 76 (SPG76) caused by a novel mutation of the CAPN1 gene, and collect the SPG76 cases published in recent years to summarize the clinical phenotype and genetic characteristics and improve the understanding of this disease. Methods:The clinical data of a patient with SPG76 caused by a mutation of the CAPN1 gene were collected, who admitted to Xiangya Hospital of Central South University on April 22, 2024. Relevant literature was searched in PubMed and China National Knowledge Infrastructure databases using the search terms "hereditary spastic paraplegia 76" "spastic paraplegia type 76" "SPG76" and a literature review was performed. Results:The patient was a 44-year-old male with the main symptoms of unsteady walking. Physical examination showed spasticity of both lower limbs, increased muscle tension of the limbs, hyperreflexia of the tendons. Brain and spinal cord magnetic resonance imaging showed no significant abnormalities. Neuroelectrophysiological examination showed no abnormalities in nerve conduction study and needle electromyography, and high amplitude F-waves were observed in the bilateral median nerves. Whole exome sequencing showed that there were compound heterozygous mutations of the CAPN1 gene: c.759+1G>A and c.1341+2T>G, of which c.1341+2T>G had not been reported. A total of 80 SPG76 cases related to CAPN1 gene mutations were reported in the literature, with an average age of onset of 25.68 years, and the clinical manifestations were mainly bilateral lower limb spasticity and tendon hyperreflexia, and about half of the patients were accompanied by upper limb spasticity and tendon hyperreflexia, ataxia, dysarthria, or lower limb weakness. Magnetic resonance imaging of the brain and spinal cord was mostly normal, and 13.8% (11/80) of the patients showed varying degrees of changes in the brain, mainly involving the cerebellum, and 5.0% (4/80) of the patients had cervical and thoracic spinal cord atrophy. The mutation types of CAPN1 gene included missense, nonsense, frameshift, and splice site variation, and the mutation sites were scattered and had no special aggregation tendency, and a total of 14 patients from 9 families carried the c.1176 G>A mutation. Conclusions:SPG76 is a rare subtype of hereditary spastic paraplegia caused by CAPN1 gene mutation, which is more common in young and middle-aged people, and patients have spasticity and tendon hyperreflexia in both lower limbs as the main clinical manifestations, most of which are accompanied by changes in the upper limbs, ataxia, etc., and a small number of patients can show atrophy of the cerebellum and (or) cervical and thoracic spinal cord by magnetic resonance of the head and spinal cord. The CAPN1 gene variants mainly include missense and nonsense variants, and c.1176G>A variant is the most prevalent pathogenic mutation site in the CAPN1 gene.