This paper summarizes the clinical experience in applying jiao （角） medicine to treat diabetes mellitus from the perspective of qi， blood， and fluids. It is believed that impaired spleen transportation and transformation is the key pathomechanism of diabetes， leading to metabolic disturbances in qi， blood， and fluids， and resulting in a sequential pathological progression of "qi → thick fluids → thin fluids → blood". At the qi level， the disease is mainly characterized by spleen qi deficiency and stagnation， and is commonly treated with Hongshen （Panax Ginseng）， Huangqi （Astragalus Mongholicus）， and Baizhu （Atractylodes Macrocephala） to tonify the spleen and regulate qi. At the thick fluids level， the condition manifests as abdominal distension， internal heat， and turbid pathogens， requiring Zexie （Alisma Orientale）， Huanglian （Coptis Chinensis）， and Dahuang （Rheum Palmatum） to clear the spleen and drain turbidity. At the thin fluids level， with qi and yin deficiency and predominant yin damage， Gegen （Pueraria Lobata）， Wuweizi （Schisandra Chinensis）， and Maidong （Ophiopogon Japonicus） are used to nourish yin and generate fluids. At the blood level， where vascular damage is predominant， Shuizhifen （Whitmania Pigra Powder）， Danshen （Salvia Miltiorrhiza）， and Sanqifen （Panax Notoginseng Powder） are applied to activate blood circulation， resolve stasis， and unblock the channels. Clinicians may flexibly select appropriate jiao medicine based on the specific pathological layer affected in each patient.

Objective:To discuss the clinical efficacy of low-temperature radiofrequency ablation assisted by endoscopy combined with resection and drainage of cervical abscess for the treatment of congenital pyriform sinus fistula （CPSF） in the acute inflammatory period of children. Methods:Clinical data of 30 patients with CPSF in the acute inflammatory period who received low-temperature radiofrequency ablation assisted by endoscopy under laryngoscope, combined with resection and drainage of cervical abscess, from January 2018 to December 2023 were reviewed. After the operation, patients were followed up closely at different stages. All patients underwent color Doppler ultrasound and electronic laryngoscopy, and the results were analyzed. Results:All 30 children successfully completed the surgery without pharyngeal fistula, dysphagia, perifistula, or distal fistula infection, and the incision in the neck healed well. The follow-up survey ranged from 6 months to 2 years, and no recurrences were observed. Conclusion:Low-temperature radiofrequency ablation assisted by endoscopy combined with resection and drainage of cervical abscess is a promising method for treating CPSF in the acute inflammatory period. It is less traumatic, simple, safe, has a significant curative effect, and a low recurrence rate. This approach can be used as a supplementary operation for CPSF in children and provides a new way for clinical treatment.
Humans ; Pyriform Sinus/abnormalities* ; Abscess/surgery* ; Drainage ; Fistula/congenital* ; Female ; Male ; Child ; Radiofrequency Ablation ; Treatment Outcome ; Postoperative Period ; Endoscopy ; Laryngoscopy ; Inflammation ; Child, Preschool

Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

Gastric cancer (GC) is characterized by high morbidity and mortality rates. Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis (Lour.) Gilg., traditionally utilized for treating asthma, cardiac ischemia, and tumors. However, comprehensive research regarding its anti-GC effects and underlying mechanisms remains limited. In this study, Chinese agarwood petroleum ether extract (CAPEE) demonstrated potent cytotoxicity against human GC cells, with half maximal inhibitory concentration (IC₅₀) values for AGS, HGC27, and MGC803 cells of 2.89, 2.46, and 2.37 μg·mL^-1, respectively, at 48 h. CAPEE significantly induced apoptosis in these GC cells, with B-cell lymphoma-2 (BCL-2) associated X protein (BAX)/BCL-2 antagonist killer 1 (BAK) likely mediating CAPEE-induced apoptosis. Furthermore, CAPEE induced G₀/G₁ phase cell cycle arrest in human GC cells via activation of the deoxyribonucleic acid (DNA) damage-p21-cyclin D1/cyclin-dependent kinase 4 (CDK4) signaling axis, and increased Fe²⁺, lipid peroxides and reactive oxygen species (ROS) levels, thereby inducing ferroptosis. Ribonucleic acid (RNA) sequencing, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses revealed CAPEE-mediated upregulation of heme oxygenase-1 (HO-1) in human GC cells. RNA interference studies demonstrated that HO-1 knockdown reduced CAPEE sensitivity and inhibited CAPEE-induced ferroptosis in human GC cells. Additionally, CAPEE administration exhibited robust in vivo anti-GC activity without significant toxicity in nude mice while inhibiting tumor cell growth and promoting apoptosis in tumor tissues. These findings indicate that CAPEE suppresses human GC cell growth through upregulation of the DNA damage-p21-cyclin D1/CDK4 signaling axis and HO-1-mediated ferroptosis, suggesting its potential as a candidate drug for GC treatment.
Animals ; Humans ; Mice ; Antineoplastic Agents, Phytogenic ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cyclin D1/genetics* ; Cyclin-Dependent Kinase 4/genetics* ; DNA Damage/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Ferroptosis/drug effects* ; G1 Phase Cell Cycle Checkpoints/drug effects* ; Heme Oxygenase-1/genetics* ; Mice, Inbred BALB C ; Mice, Nude ; Plant Extracts/pharmacology* ; Stomach Neoplasms/physiopathology* ; Thymelaeaceae/chemistry* ; Up-Regulation/drug effects*

Objective:This study aims to summarize the surgical efficacy of macroglossia reduction combined with radiofrequency ablation of Beckwith-Wiedemann Syndrome (BWS).Methods:A retrospective analysis was conducted on the clinical data of patients with macroglossia who received treatment at the Department of Otolaryngology-Head and Neck Surgery, Xiamen Children’s Hospital between May 2019 and July 2022. All patients with macroglossia underwent either one-stage or staged anterior tongue V-shaped incision massive resection, followed by needle tip low-temperature plasma radiofrequency ablation on the lateral and base of the tongue. The postoperative complications in pediatric patients were monitored, including the incision shape of the tongue body, restoration of tongue body structure and function. MRI scans of the tongue were performed at 3 and 12 months post-operation to evaluate tissue healing, changes in tongue volume, and whether there was successful retraction of the enlarged tongue into the oral cavity for evaluating treatment efficacy (cured or not cured).Results:The study included 70 cases, comprising 31 male and 39 female patients, with an average age of 15.4 months (ranging from 5 months to 4 years old). Among them, 68 cases underwent macroglossia reduction combined with radiofrequency ablation at the same time, and 2 cases underwent macroglossia reduction surgery first in other hospitals, and tongue body radiofrequency ablation was performed one year after the surgery. All children were followed up foran average follow-up time of 18 months (6 to 36 months). There were no serious complications such as massive hemorrhage and tongue hematoma. After the operation, 14 cases of superficial rupture of tongue tip wound were gradually improved after 5-7 days of no oral eating, and recovered after 4-12 weeks of liquid diet. Thirteen cases had suture reactions in the tongue back, which were self-resolving within 2 to 3 weeks with no special treatment. All patients showed significant reduction in tongue size after the surgery, which could be completely inserted into the oral cavity, and the treatment effect was satisfactory.Conclusion:Macroglossia reduction combined with radiofrequency ablation is a feasible and effective method for the treatment of BWS with macroglossia and is recommended for application.

Objective:This study aims to summarize the surgical efficacy of macroglossia reduction combined with radiofrequency ablation of Beckwith-Wiedemann Syndrome (BWS).Methods:A retrospective analysis was conducted on the clinical data of patients with macroglossia who received treatment at the Department of Otolaryngology-Head and Neck Surgery, Xiamen Children’s Hospital between May 2019 and July 2022. All patients with macroglossia underwent either one-stage or staged anterior tongue V-shaped incision massive resection, followed by needle tip low-temperature plasma radiofrequency ablation on the lateral and base of the tongue. The postoperative complications in pediatric patients were monitored, including the incision shape of the tongue body, restoration of tongue body structure and function. MRI scans of the tongue were performed at 3 and 12 months post-operation to evaluate tissue healing, changes in tongue volume, and whether there was successful retraction of the enlarged tongue into the oral cavity for evaluating treatment efficacy (cured or not cured).Results:The study included 70 cases, comprising 31 male and 39 female patients, with an average age of 15.4 months (ranging from 5 months to 4 years old). Among them, 68 cases underwent macroglossia reduction combined with radiofrequency ablation at the same time, and 2 cases underwent macroglossia reduction surgery first in other hospitals, and tongue body radiofrequency ablation was performed one year after the surgery. All children were followed up foran average follow-up time of 18 months (6 to 36 months). There were no serious complications such as massive hemorrhage and tongue hematoma. After the operation, 14 cases of superficial rupture of tongue tip wound were gradually improved after 5-7 days of no oral eating, and recovered after 4-12 weeks of liquid diet. Thirteen cases had suture reactions in the tongue back, which were self-resolving within 2 to 3 weeks with no special treatment. All patients showed significant reduction in tongue size after the surgery, which could be completely inserted into the oral cavity, and the treatment effect was satisfactory.Conclusion:Macroglossia reduction combined with radiofrequency ablation is a feasible and effective method for the treatment of BWS with macroglossia and is recommended for application.

Background::The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.Methods::We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.Results::We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.Conclusions::REDH is accessible at http://www.redhdatabase.com/. This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

Objective:Trigeminal neuralgia(TN)is a severe chronic neuropathic pain that mainly affects the distribution area of the trigeminal nerve with limited treating efficacy.There are numerous treatments for TN,but currently the main clinical approach is to suppress pain by carbamazepine(CBZ).Brain-derived neurotrophic factor(BDNF)is closely related to chronic pain.This study aims to determine the effects of CBZ treatment on BDNF expression in both the trigeminal ganglion(TG)and serum of TN via a chronic constriction injury of the infraorbital nerve(ION-CCI)rat model. Methods:The ION-CCI models were established in male Sprague-Dawley rats and were randomly divided into a sham group,a TN group,a TN+low-dose CBZ treatment group(TN+20 mg/kg CBZ group),a TN+medium-dose CBZ treatment group(TN+40 mg/kg CBZ group),and a TN+high-dose CBZ treatment group(TN+80 mg/kg CBZ group).The mechanical pain threshold in each group of rats was measured regularly before and after surgery.The expressions of BDNF and tyrosine kinase receptor B(TrkB)mRNA in TGs of rats in different groups were determined by real-time PCR,and the expression of BDNF protein on neurons in TGs was observed by immunofluorescence.Western Blotting was used to detect the protein expression of BDNF,TrkB,extracellular regulated protein kinases(ERK),and phospho-extracellular regulated protein kinases(p-ERK)in TGs of rats in different groups.The expression of BDNF in the serum of rats in different groups was detected by enzyme-linked immunosorbent assay(ELISA). Results:The results of mechanical pain sensitivity showed that there was no significant difference in the mechanical pain threshold in the right facial sensory area of the experimental rats in each group before surgery(all P>0.05).From the 3rd day after operation,the mechanical pain threshold of rats in the TN group was significantly lower than that in the sham group(all P<0.01),and the mechanical pain threshold of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 CBZ mg/kg group was higher than that in the TN group(all P<0.05).The BDNF and TrkB mRNA and protein expressions in TGs of rats in the TN group were higher than those in the sham group(all P<0.05),and those in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than the TN group(all P<0.05).The p-ERK levels in TG of rats in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were significantly decreased compared with the TN group(all P<0.05).The BDNF and neuron-specific nuclear protein(NeuN)were mainly co-expressed in neuron of TGs in the TN group and they were significantly higher than those in the sham group(all P<0.05).The co-labeled expressions of BDNF and NeuN in TGs of the TN+ 80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).The results of ELISA showed that the level of BDNF in the serum of the TN group was significantly higher than that in the sham group(P<0.05).The levels of BDNF in the TN+80 mg/kg CBZ group,the TN+40 mg/kg CBZ group,and the TN+20 mg/kg CBZ group were lower than those in the TN group(all P<0.05).Spearman correlation analysis showed that the BDNF level in serum was negatively correlated with mechanical pain threshold(r=-0.650,P<0.01). Conclusion:CBZ treatment can inhibit the expression of BDNF and TrkB in the TGs of TN rats,reduce the level of BDNF in serum of TN rats and the phosphorylation of ERK signaling pathway,so as to inhibit TN.The serum level of BDNF can be considered as an indicator for the diagnosis and prognosis of TN.

Purpose To explore the clinical and pathologi-cal features and the relationships between pathological features and drugs of patients with drug-induced liver injury(DILI)based on the hepatotoxicity injury patterns.Methods The clin-ical data,laboratory indicators,drugs,and liver biopsy of 50 cases of DILI were collected,the expression of CK19 was detec-ted by immunohistochemistry EnVision two-step method,and the reticular scaffold of liver tissue was displayed by Reticular fiber staining.Results Among the 50 patients with DILI,there were 29 cases of hepatocellular DILI,11 cases of cholestatic DILI,and 10 cases of mixed DILI,respectively,with the hepatocellu-lar DILI accounting for the highest proportion(58％).7 catego-ries of drugs induced DILI,with herbal ranking first(52％).Different types of drugs could cause different types of DILI,with herbal induced 17 cases hepatocellular DILI(58.62％)and an-ti-infectious and anticancer drugs induced all 3 cases cholestatic DILI(27.27％).Different types of DILI displayed various pathological characteristics.Hepatocellular congestion,feathery degeneration,and small bile duct thrombosis primarily occur in cholestasis and mixed DILI,while bridging necrosis,sub-large and large necrosis were mainly seen in hepatocellular DILI.Conclusion Based on hepatotoxicity injury patterns,DILI ex-hibits a variety of clinical and pathological characteristics,and there is some relationship between pathological characteristics and drugs.Liver puncture pathological biopsy plays an important role in improving the diagnosis and treatment of DILI.