ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked （DDX3X） in immune-mediated liver injury （ILI）， and to clarify its mechanism by regulating endoplasmic reticulum stress （ERS）-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A （ConA） via the caudal vein to establish a model of ILI， PBS （control group） and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice （DDX3X^ΔHep and DDX3X-flox mice （DDX3X^fl/fl）， respectively.. The log-rank survival analysis， measurement of the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）， and HE staining of liver tissue were performed to assess liver injury， and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid （4-PBA， 100 mg/kg） was performed to inhibit ERS. Serum samples （n=30） and liver tissue samples （n=6） were collected from healthy controls， chronic hepatitis B （CHB） patients， and hepatitis B virus-associated liver failure （HBV-LF） patients； ELISA was used to measure the serum level of DDX3X， and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice， the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury （P<0.05）， and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% （compared with 20% in the DDX3X^fl/fl group）， with significant reductions in the serum levels of ALT and AST （P<0.000 1） and the expression levels of the ERS markers GRP78 and CHOP （P<0.05）. After ERS was inhibited by 4-PBA， there was alleviation of liver injury （with reductions in ALT and AST， P <0.001） and a reduction in DDX3X expression （P<0.01）. The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls （all P<0.01）， and there was a significant increase in the serum level of DDX3X in HBV-LF patients （P<0.000 1）. ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway （GRP78/CHOP）， and its expression is associated with the progression of hepatitis B. Therefore， it can be used as a potential therapeutic target.

Metabolic diseases have seen a steady increase in incidence in recent years, becoming one of the main causes of sub-health status globally. Neutrophil extracellular traps(NETs) are reticular complexes containing DNA, which trap foreign microorganisms or induce an immune response. Current research indicates that NETs are widely active in various metabolic diseases and can cause severe damage to the body through multiple mechanisms, including promoting blood glucose elevation, damaging vascular endothelial cells, forming vascular embolisms, triggering intense inflammation, and promoting lipid accumulation. Therefore, intervening in NETs is an important approach to treating metabolic diseases. Research has shown a close relationship between the theory of spleen heat-turbid toxin theory and metabolic diseases-NETs mechanism. The basic pathogenesis include the internal accumulation of phlegm-dampness, qi stagnation and blood stasis, internal accumulation of dampness-heat, phlegm and blood stasis, and flourishing toxic heat. Various Chinese herbal medicines with the functions of dispelling dampness, resolving phlegm, promoting blood circulation to remove blood stasis, and clearing heat and toxins, along with their extracts and compound prescriptions, can treat metabolic diseases by regulating NETs and delaying disease progression. This paper systematically outlined the formation mechanisms of NETs, their connection to metabolic diseases, the theoretical basis in TCM, their roles in numerous metabolic diseases, and the current research status of TCM in regulating NETs to prevent and control metabolic diseases, aiming to provide effective reference ideas for developing therapeutic strategies for metabolic diseases.
Humans ; Extracellular Traps/metabolism* ; Metabolic Diseases/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Neutrophils/metabolism* ; Medicine, Chinese Traditional

In recent years， hyperuricemia （HUA） has shown a rapidly increasing incidence and tends to occur in increasingly young people， with a wide range of cardiac， renal， joint， and cancerous hazards and all-cause mortality associations. Western medicine treatment has limitations such as large liver and kidney damage， medication restriction， and easy recurrence. The intestine is the major extra-renal excretion pathway for uric acid （UA）， and the intestinal microecology can be regulated to promote UA degradation. It offers great potential to develop UA-lowering strategies that target the intestinal microecology， which are promising to provide safer and more effective therapeutic approaches. Traditional Chinese medicine （TCM） can treat HUA via multiple targets and multiple pathways from a holistic view， with low toxicity and side effects. Studies have shown that intestinal microecology is a crucial target for TCM in the treatment of HUA. However， its specific mechanism of action has not been fully elucidated. Focusing on the key role of intestinal microecology in HUA， this review explores the relationship between intestinal microecology and HUA in terms of intestinal flora， intestinal metabolites， intestinal UA transporters， and intestinal barriers. Furthermore， we summarize the research progress in TCM treatment of HUA by targeting the intestinal microecology， with the aim of providing references for the development of TCM intervention strategies for HUA and the direction of future research.

Objective:To investigate the clinical features, imaging characteristics, surgical strategies, and therapeutic outcomes of otitis media complicated with inflammatory response of local meninges.Methods:A retrospective analysis was conducted on the clinical data of 8 patients with chronic suppurative otitis media complicated with inflammatory response of local meninges, treated by the Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital from 2019 to 2023. Appropriate surgical strategies were selected based on the patient′s clinical manifestations, imaging characteristics, extent of lesions, and facial nerve function. Follow-up was performed postoperatively to assess the therapeutic outcomes.Results:Among the eight patients, there were six males and two females, with an average age of (55.9±12.6) years old. The primary clinical manifestations included otorrhea, hearing loss, facial paralysis, earache, headache, and fever. All patients had a history of chronic suppurative otitis media and tympanic membrane perforation, with varying degrees and types of hearing loss. Seven patients presented with peripheral facial palsy preoperatively, with the House-Brackmann (H-B) grading scale as follows: 4 cases (4/7) in grade Ⅳ, 1 case (1/7) in grade Ⅴ, and 2 cases (2/7) in grade Ⅵ. The mean duration of otorrhea and/or hearing loss was (24.68±12.18) years, while, the average duration of severe headache, aggravated otorrhea and facial paralysis was (2.73±3.92) months. Preoperative high-resolution CT scan of the temporal bone revealed soft tissue shadow in the middle ear and mastoid process, with partial defects in the mastoid cortex. Cranial MRI T1WI showed high signal in the meninges on the affected side, with contrast-enhanced MRI indicating localized meningeal thickening. Four patients (4/8) had diabetes mellitus, and 2 patients (2/8) had a history of middle ear/mastoid surgery. All patients underwent surgical treatment, including thorough removal of lesions, adequate drainage, and facial nerve decompression. Tympanoplasty and hearing reconstruction were performed when conditions permitted. Specifically, 5 patients underwent intact canal wall radical mastoidectomy with facial nerve decompression and tympanoplasty, 2 patients underwent canal wall down mastoidectomy with facial nerve exploration decompression, and 1 patient underwent modified radical mastoidectomy. Postoperatively, patients experienced significant relief and gradual disappearance of ear and head pain. The postoperative H-B grading scale of facial nerve function was as follows: 4 cases in grade Ⅰ (4/8, including 1 case without preoperatively facial palsy), 2 cases (2/8) in grade Ⅱ, and 2 cases (2/8) in grade Ⅲ. Postoperative cranial MRI showed a significant reduction in localized meningeal thickening on the affected side.Conclusions:Patients with long-term chronic suppurative otitis media and/or cholesteatoma who suddenly presented with headache, fever, aggravated otorrhea, and facial paralysis should be suspected of having inflammatory response of local meninges. High-resolution CT of temporal bone and cranial MRI provide crucial diagnostic information. Early surgical exploration and thorough lesion removal are effective treatment methods.

Objective To investigate the screening results and factors affecting abnormal detection rates among high-risk groups of esophageal cancer and to explore effective intervention measures. Methods We investigated and collected the information on gender, education level, age, marital status, symptoms of reflux esophagitis (heartburn, acid reflux, belching, hiccup, foreign body sensation in the pharynx, and difficulty swallowing), consumption of pickled vegetables, salt use, and esophageal cancer incidence of villagers in a natural village in Wenfeng District, Anyang City, Henan Province. Changes in reflux esophagitis symptoms in the high-incidence area of esophageal cancer before and after 16 years were observed, and the relationship of such changes with esophageal cancer was analyzed. Results In 2008, 711 cases were epidemiologically investigated, including 213 cases with one of the symptoms of reflux esophagitis such as heartburn, acid reflux, belching, hiccups, foreign body sensation in the pharynx, and difficulty swallowing (sorted in accordance with the abovementioned symptoms; if there are multiple symptoms, then the former is taken); 55 cases with at least two related symptoms, among which the most symptom was heartburn in 108 cases (15.1%); followed by acid reflux, belching, etc. In 2024, the same group of people was investigated, and eight people were missing because of relocation. A total of 703 people were successfully investigated, of which 189 cases (26.8%) had one of the symptoms of reflux esophagitis, such as heartburn (sorted in accordance with relevant symptoms, if there are multiple symptoms, then the former will be selected); 167 cases (23.7%) had at least two related symptoms, among which the most symptom was heartburn in 139 cases (19.7%); followed by acid reflux. Over 16 years, among the 703 people investigated, 45 cases had esophageal cancer and they had one or more of the abovementioned symptoms. No significant differences in the reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.26); no significant differences in the composition of reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.299). Conclusion The detection rate of reflux esophagitis-related symptoms in the population in a high-risk area of esophageal cancer has not decreased in the past 16 years, and the high-risk factors still exist. Esophageal cancer is closely related to reflux esophagitis, and clinical practice can provide early diagnosis and treatment for high-risk population.

Objective:To explore the efficacy and adverse reactions of CAG regimen combined with venetoclax,chidamide,and azacitidine in the treatment of elderly patients with acute myeloid leukemia(AML).Methods:15 elderly AML patients aged ≥ 60 years old who were admitted to the Hematology Department of our hospital from May 2022 to October 2023 were treated with the CAG regimen combined with venetoclax,chidamide and azacitidine,and the efficacy,treatment-related adverse events,overall survival(OS)and event-free survival(EFS)were analyzed.Results:After one course of treatment,11 out of 15 patients achieved complete response(CR),3 patients achieved CR with incomplete hematologic recovery(CRi),and 1 patient died due to prior infection before efficacy evaluation,and the overall response rate(ORR)was 93.3％(14/15).The median follow-up time was 131(19-275)days,with median OS and EFS both remaining unreached.Next-generation sequencing(NGS)analysis showed that among the 15 patients,13 were detected with gene mutations,and there were 7 genes with mutation frequencies of more than 10％,including ASXL1(4 cases),RUNX1(4 cases),BCOR(3 cases),DNMT3A(3 cases),STAG2(2 cases),IDH1/2(2 cases),and TET(2 cases).Among the 13 patients with detectable mutations,12 patients achieved composite response(CR+CRi).The average recovery time of white blood cell count was 14.6 days after chemotherapy,and the average recovery time of platelets was 7.7 days after chemotherapy.The main adverse event was myelosuppression,with 10 patients accompanied by infection.Except for 1 patient who died due to septic shock during chemotherapy,no patients experienced serious complications such as heart,liver,or kidney damage during the treatment process.Conclusion:The CACAG+V regimen,which combines the CAG regimen with venetoclax,chidamide,and azacitidine,can be applied in the treatment of elderly AML patients,demonstrating good safety and induction remission rate.

Objective:To investigate the clinical features, imaging characteristics, surgical strategies, and therapeutic outcomes of otitis media complicated with inflammatory response of local meninges.Methods:A retrospective analysis was conducted on the clinical data of 8 patients with chronic suppurative otitis media complicated with inflammatory response of local meninges, treated by the Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital from 2019 to 2023. Appropriate surgical strategies were selected based on the patient′s clinical manifestations, imaging characteristics, extent of lesions, and facial nerve function. Follow-up was performed postoperatively to assess the therapeutic outcomes.Results:Among the eight patients, there were six males and two females, with an average age of (55.9±12.6) years old. The primary clinical manifestations included otorrhea, hearing loss, facial paralysis, earache, headache, and fever. All patients had a history of chronic suppurative otitis media and tympanic membrane perforation, with varying degrees and types of hearing loss. Seven patients presented with peripheral facial palsy preoperatively, with the House-Brackmann (H-B) grading scale as follows: 4 cases (4/7) in grade Ⅳ, 1 case (1/7) in grade Ⅴ, and 2 cases (2/7) in grade Ⅵ. The mean duration of otorrhea and/or hearing loss was (24.68±12.18) years, while, the average duration of severe headache, aggravated otorrhea and facial paralysis was (2.73±3.92) months. Preoperative high-resolution CT scan of the temporal bone revealed soft tissue shadow in the middle ear and mastoid process, with partial defects in the mastoid cortex. Cranial MRI T1WI showed high signal in the meninges on the affected side, with contrast-enhanced MRI indicating localized meningeal thickening. Four patients (4/8) had diabetes mellitus, and 2 patients (2/8) had a history of middle ear/mastoid surgery. All patients underwent surgical treatment, including thorough removal of lesions, adequate drainage, and facial nerve decompression. Tympanoplasty and hearing reconstruction were performed when conditions permitted. Specifically, 5 patients underwent intact canal wall radical mastoidectomy with facial nerve decompression and tympanoplasty, 2 patients underwent canal wall down mastoidectomy with facial nerve exploration decompression, and 1 patient underwent modified radical mastoidectomy. Postoperatively, patients experienced significant relief and gradual disappearance of ear and head pain. The postoperative H-B grading scale of facial nerve function was as follows: 4 cases in grade Ⅰ (4/8, including 1 case without preoperatively facial palsy), 2 cases (2/8) in grade Ⅱ, and 2 cases (2/8) in grade Ⅲ. Postoperative cranial MRI showed a significant reduction in localized meningeal thickening on the affected side.Conclusions:Patients with long-term chronic suppurative otitis media and/or cholesteatoma who suddenly presented with headache, fever, aggravated otorrhea, and facial paralysis should be suspected of having inflammatory response of local meninges. High-resolution CT of temporal bone and cranial MRI provide crucial diagnostic information. Early surgical exploration and thorough lesion removal are effective treatment methods.

Objective:To identify the gene mutation types of 4 suspected β-thalassemia patients in Yunnan Province,and to analyze the genotypes and hematological phenotypes.Methods:Whole genome sequencing was performed on the samples of 4 suspected β-thalassemia patients from the Dai ethnic group in a thalassemia endemic area of Yunnan Province,whose hematological phenotypes were not consistent with the results of common thalassemia gene mutations.The mutations of β-globin gene clusters were confirmed by polymerase chain reaction(PCR)and Sanger DNA sequencing technology.Results:The 3.5 kb deletion in β-globin gene cluster(NC_000011.10:g.5224302-5227791 del3490bp)was detected in 4 patients'samples,of which 1 case was also detected with HbE mutation and 1 case with CD17 mutation.These 2 patients displayed moderate anemia phenotype,while the two patients with only the 3.5 kb deletion presented with other mild anemia phenotype.Conclusion:Heterozygous carriers with rare 3.5 kb deletion of the β-globin gene cluster may develop mild anemia,compound mutations of the 3.5 kb deletion with other mutations may led to intermediate thalasemia with moderate to sever anemia.In areas with a high incidence of thalassemia,suspected patients should undergo genetic testing to avoid missing or misdiagnosing rare mutations.

Objective To analyze the clinical characteristics and prognosis of patients with coronary slow flow(CSF)or no reflow(CNR)after emergency PCI.Methods A total of 443 elderly STEMI patients who underwent emergency PCI in Department of Cardiology of the First Affilia-ted Hospital of Tsinghua University from January 2017 to August 2023 were recruited,and ac-cording to thrombolysis in myocardial infarction(TIMI)flow grading after operation,they were divided into CSF/CNR group(TIMI grade≤2 flow,n=40)and normal flow(NCF)group(TIMI grade 3 flow,n=403).Logistic regression analysis was used to analyze the risk factors for CSF/CNR in STEMI patients after PCI.The prognosis was analyzed in the two groups.Results The CSF/CNR group had advanced age,longer durations from onset to admission and from onset to balloon opening,higher mortality rate,and larger proportions of chronic heart failure(CHF),type 2 diabetes mellitus(T2DM),pulse rate＞100 times/min,SBP＜100 mm Hg(1 mm Hg=0.133 kPa),Killip grade＞1,left anterior descending artery disease,LVEF＜50％,and using glycopro-tein Ⅱb/Ⅲa inhibitors and intraaortic balloon counterpulsation,but lower male ratio and DBP when compared with the control group(P＜0.05,P＜0.01).Multiple logistic regression analysis revealed that T2DM(OR=1.320,95％CI:0.618-2.123,P=0.046),mean SBP(OR=1.239,95％CI:0.752-1.525,P=0.04)and SBP＜100 mm Hg(OR=1.330,95％CI:0.836-1.675,P=0.013)were independent risk factors,while male was a protective factor(OR=-1.755,95％CI:-2.338--1.171,P=0.002)for CSF/CNR in STEMI patients after PCI.Conclusion T2DM and lower SBP are independent risk factors,while male is a protective factor for CSF/CNR in STEMI patients after emergency PCI.

Purpose: This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis. Methods: This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up. Results: No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered. Conclusion CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes.