OBJECTIVE: To illustrate the role of dehydrocorydaline (DHC) in chronic constriction injury (CCI)-induced neuropathic pain and the underlying mechanism. METHODS: C57BL/6J mice were randomly divided into 3 groups by using a random number table, including sham group (sham operation), CCI group [intrathecal injection of 10% dimethyl sulfoxide (DMSO)], and CCI+DHC group (intrathecal injection of DHC), 8 mice in each group. A CCI mouse model was conducted to induce neuropathic pain through ligating the right common sciatic nerve. On day 14 after CCI modeling or sham operation, mice were intrathecal injected with 5 µL of 10% DMSO or 10 mg/kg DHC (5 µL) into the 5th to 6th lumbar intervertebral space (L5-L6). Pregnant ICR mice were sacrificed for isolating primary spinal neurons on day 14 of embryo development for in vitro experiment. Pain behaviors were evaluated by measuring the paw withdrawal mechanical threshold (PWMT) of mice. Immunofluorescence was used to observe the activation of astrocytes and microglia in mouse spinal cord. Protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), phosphorylation of N-methyl-D-aspartate receptor subunit 2B (p-NR2B), and NR2B in the spinal cord or primary spinal neurons were detected by Western blot. RESULTS: In CCI-induced neuropathic pain model, mice presented significantly decreased PWMT, activation of glial cells, overexpressions of iNOS, TNF-α, IL-6, and higher p-NR2B/NR2B ratio in the spinal cord (P<0.05 or P<0.01), which were all reversed by a single intrathecal injection of DHC (P<0.05 or P<0.01). The p-NR2B/NR2B ratio in primary spinal neurons were also inhibited after DHC treatment (P<0.05). CONCLUSION An intrathecal injection of DHC relieved CCI-induced neuropathic pain in mice by inhibiting the neuroinflammation and neuron hyperactivity.
Animals ; Neuralgia/etiology* ; Mice, Inbred C57BL ; Analgesics/pharmacology* ; Neuroinflammatory Diseases/pathology* ; Constriction ; Male ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; Mice, Inbred ICR ; Microglia/pathology* ; Spinal Cord/drug effects* ; Female ; Mice ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Constriction, Pathologic/complications* ; Interleukin-6/metabolism* ; Astrocytes/metabolism* ; Chronic Disease ; Neurons/metabolism*

OBJECTIVES: Endometrial tuberculosis, which commonly affects women of reproductive age, is a significant cause of intrauterine adhesions (IUA), potentially leading to hypomenorrhea, amenorrhea, and infertility. Hysteroscopic adhesiolysis is the primary treatment for IUA; however, studies specifically addressing its efficacy in tuberculosis-induced IUA remain scarce. This study aims to evaluate the therapeutic outcomes of hysteroscopic adhesiolysis for IUA caused by endometrial tuberculosis. METHODS: This retrospective cohort study included patients diagnosed with tuberculosis-induced IUA who underwent hysteroscopic adhesiolysis at the Third Xiangya Hospital of Central South University between May 2014 and October 2022. Clinical data including age, medical history, adhesion severity, surgical treatment, and reproductive outcomes were analyzed. RESULTS: Among 39 patients identified, 2 were lost to follow-up. A total of 37 patients were included, with a follow-up duration ranging from 6 months to 9 years. Hypomenorrhea was reported in 24 (64.9%) patients, secondary amenorrhea in 10 (27.0%) patients, and normal menstruation in 3 (8.1%) patients. Most patients presented with primary infertility (59.5%), and only 2 (5.4%) had secondary infertility. The median American Fertility Society (AFS) score at initial assessment was 10 (range, 8-12); 8 (21.6%) patients had moderate IUA, and 29 (78.4%) had severe IUA. A total of 86 surgical procedures were performed across 37 patients, with 27 patients undergoing 2 or more surgeries. Postoperatively, 25 (67.6%) patients achieved normalization of the uterine cavity, while 12 (32.4%) still had a reduced cavity. Only 7 (18.9%) patients had a grossly normal endometrium at the final surgery, all of whom had moderate adhesions at the initial procedure. Menstrual flow returned to normal in 12 (32.4%) patients, while 25 (67.6%) continued to experience hypomenorrhea. Of 29 patients who attempted in vitro fertilization and embryo transfer (IVF-ET), only 6 (20.7%) conceived. Among these, 4 (13.8%) delivered at term via cesarean section; one case was complicated by postpartum hemorrhage due to uterine atony and another by placental adhesion. CONCLUSIONS Endometrial tuberculosis can lead to severe IUA. Hysteroscopic adhesiolysis facilitates cavity restoration and improvement of menstrual conditions, but the overall reproductive outcomes remain suboptimal.
Humans ; Female ; Hysteroscopy/methods* ; Tissue Adhesions/etiology* ; Retrospective Studies ; Adult ; Uterine Diseases/etiology* ; Infertility, Female/surgery* ; Treatment Outcome ; Tuberculosis, Female Genital/surgery* ; Fertility ; Pregnancy

Tubal ciliary movement is one of the essential transport mechanisms for female fertility, playing a key role in facilitating oocyte pickup and transporting the fertilized ovum. This movement is mediated by multiciliated cells and regulated by specific proteins and hormones that modulate ciliary number, length, polarity, beat frequency, and amplitude to ensure proper function. Genetic mutations, inflammatory stimuli, and hormonal fluctuations can impair ciliary activity or induce ciliary apoptosis, leading to ciliary dysfunction. Disorders of tubal ciliary movement are frequently observed in primary ciliary dyskinesia, pelvic inflammatory disease, polycystic ovary syndrome, and endometriosis, conditions commonly associated with female infertility. These disorders manifest as structural abnormalities of cilia, disrupted polarity, shortened ciliary length, reduced ciliary count, and decreased beat frequency and amplitude. Understanding the role of tubal ciliary movement in female infertility-related diseases, through immunohistochemistry and ultrastructural analysis, helps clarify underlying infertility mechanisms. Identifying abnormal inflammatory factors, hormonal environments, and gene expression, combined with advanced techniques for measuring ciliary protein and beat frequency, may offer novel clinical targets for early prevention and treatment of female infertility.
Humans ; Female ; Infertility, Female/etiology* ; Cilia/physiology* ; Polycystic Ovary Syndrome/physiopathology* ; Fallopian Tubes/physiopathology* ; Endometriosis/complications* ; Pelvic Inflammatory Disease/complications*

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is a rare autosomal dominant hereditary disorder characterized by multisystem vascular malformations, including mucocutaneous telangiectasia and arteriovenous malformations. This paper reports a case of a male patient with HHT admitted to the Second Xiangya Hospital of Central South University who presented with hemoptysis, an uncommon manifestation in HHT. Imaging revealed bilateral bronchial artery dilatation and tortuosity, as well as bilateral pulmonary artery enlargement. Whole-exome sequencing for monogenic disorders ultimately identified an ACVRL1 gene mutation, confirming a diagnosis of HHT type 2. Diagnosis of HHT is primarily based on clinical manifestations, imaging findings, and family history, while genetic testing facilitates definitive diagnosis and subtyping. Anti-angiogenic therapy has proven to be an effective and safe treatment approach for controlling hemoptysis, epistaxis, and gastrointestinal bleeding in HHT patients. This case highlights the importance of early genetic screening in suspected cases to enable timely etiological clarification and intervention.
Humans ; Telangiectasia, Hereditary Hemorrhagic/diagnosis* ; Hemoptysis/etiology* ; Male ; Activin Receptors, Type II/genetics* ; Mutation

OBJECTIVES: Hypertriglyceridemic acute pancreatitis (HTG-AP) has a rapid onset and is associated with a high risk of progression and recurrence. Early identification of patients at risk of severe disease can help reduce the likelihood of multiple organ failure and mortality. This study aims to investigate the changes in inflammatory composite markers and D-dimer (D-D) levels in young and middle-aged/elderly patients with HTG-AP and to evaluate their predictive value for disease progression. METHODS: A total of 230 patients with HTG-AP admitted to Chongqing University Jiangjin Hospital (Jiangjin Central Hospital) between 2017 and 2023 were retrospectively enrolled. Patients were first divided into a young group (≤45 years) and a middle-aged/elderly group (>45 years), and then stratified into mild and severe groups based on disease severity. Inflammatory composite markers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein-to-lymphocyte ratio (CLR), systemic inflammation response index (SIRI), systemic immune inflammation index (SII), as well as D-D levels, were compared among groups. Least absolute shrinkage and selection operator (LASSO) regression and Logistic regression were used to identify independent risk factors for disease progression in each age group. Receiver operating characteristic (ROC) curves and the DeLong test were used to assess and compare the predictive performance (area under the curve, AUC) of risk factors. Internal validation was performed using the bootstrap method (n=1 000). RESULTS: No significant differences in NLR, PLR, MLR, SIRI, SII, CLR, or D-D levels were observed between the young (n=127) and middle-aged/elderly (n=103) groups (all P>0.05). Among young patients, the severe group (n=59) had significantly higher NLR, SIRI, SII, CLR, and D-D levels compared to the mild group (n=68) (all P<0.05). Among middle-aged/elderly patients, CLR and D-D levels were significantly higher in the severe group (n=49) than in the mild group (n=54) (P<0.05). LASSO and Logistic regression analyses identified elevated D-D as an independent risk factor for disease progression in young patients (P=0.007, OR=1.458, 95% CI 1.107 to 1.920), while both D-D (P=0.001, OR=2.267, 95% CI 1.413 to 3.637) and CLR (P=0.003, OR=1.007, 95% CI 1.003 to 1.012) were independent risk factors in middle-aged/elderly patients. ROC analysis showed that D-D predicted disease progression in young and middle-aged/elderly patients with AUCs of 0.653 and 0.741, sensitivities of 67.8% and 57.1%, and specificities of 72.1% and 88.9%, respectively. CLR predicted progression in middle-aged/elderly patients with an AUC of 0.687, sensitivity of 63.3%, and specificity of 70.4%. DeLong test showed no significant difference in AUC between D-D and CLR for middle-aged/elderly patients (Z=0.993, P=0.321). Internal validation via bootstrap analysis yielded a D-D AUC of 0.732, with sensitivity and specificity of 68.1% and 91.0%, respectively. CONCLUSIONS Differences in inflammatory response and coagulation function exist across age groups and disease severities in HTG-AP patients. Elevated D-D is an independent predictor of disease progression in both young and middle-aged/elderly patients, while CLR also predicts progression in the latter group. D-D, in particular, demonstrates strong predictive value for severe disease in middle-aged/elderly patients with HTG-AP.
Humans ; Fibrin Fibrinogen Degradation Products/metabolism* ; Disease Progression ; Middle Aged ; Pancreatitis/etiology* ; Male ; Female ; Retrospective Studies ; Adult ; Biomarkers/blood* ; Hypertriglyceridemia/blood* ; Acute Disease ; Predictive Value of Tests ; Aged ; Inflammation ; C-Reactive Protein/analysis* ; Neutrophils ; Age Factors

OBJECTIVES: Psoriasis is associated with lipid metabolism disorders, but the underlying mechanisms remain unclear. This study aims to investigate the role of trimethylamine N-oxide (TMAO) in lipid metabolism dysregulation in psoriasis. METHODS: An imiquimod (IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters, TMAO levels, and liver flavin monooxygenase 3 (FMO3) mRNA expression. Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles. To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model, exogenous TMAO, choline, or 3,3-dimethyl-1-butanol (DMB) were administered via intraperitoneal injections or diet in IMQ-treated mice. Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways. RESULTS: IMQ-induced psoriatic mice exhibited abnormal glucose, insulin, and lipid levels. IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2 (Glut2) and silence information regulator 1 (Sirt1), while upregulating glucose transporter 4 (Glut4) and peroxisome proliferator-activated receptor gamma (PPARγ). Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice. Additionally, liver FMO3 mRNA expression was increased in the psoriatic mouse model. In patients, TMAO levels positively correlated with Psoriasis Area and Severity Index (PASI) scores, serum triglyceride (TG), and total cholesterol (TC) levels. The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice. A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice, whereas DMB treatment alleviated these effects. RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122 (miR-122), which may suppress the expression of gremlin 2 (GREM2), thus contributing to lipid metabolism disorder. CONCLUSIONS TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.
Animals ; Methylamines/blood* ; Mice ; Psoriasis/chemically induced* ; Lipid Metabolism/drug effects* ; Humans ; Male ; Liver/metabolism* ; Female ; Oxygenases/genetics* ; Disease Models, Animal ; Lipid Metabolism Disorders/etiology* ; Adult ; Mice, Inbred C57BL

OBJECTIVES: Transcervical resection of adhesions (TCRA) under hysteroscopy is the mainstay treatment for intrauterine adhesions (IUA), but its effectiveness varies depending on the surgical approach. This study aims to investigate the impact of different surgical techniques on endometrial repair and pregnancy outcomes in patients with secondary infertility and moderate-to-severe IUA. METHODS: A retrospective analysis was conducted on 225 patients who underwent TCRA followed by in vitro fertilization and embryo transfer between January 2021 and December 2022. Patients were grouped based on the surgical method: A cold knife group (n=127) and an electrosurgical group (n=98). Adhesions were separated using either cold knife or electrosurgical instruments. Postoperative visualization of uterine angle and tubal ostia, endometrial restoration, vascular endothelial growth factor (VEGF) expression in adhesion tissues, and clinical pregnancy outcomes were compared. Univariate and multivariate Logistic regression analyses were performed to identify factors influencing pregnancy outcomes. A LightGBM model was constructed to predict pregnancy outcomes. RESULTS: Compared with the electrosurgical group, patients in the cold knife group had significantly greater postoperative endometrial thickness [(8.86±0.53) mm vs (8.10±0.87) mm, P<0.05], higher live birth rates (64.57% vs 30.61%, P<0.05), and lower VEGF expression (1.31±0.09 vs 1.53±0.16, P<0.05). Logistic regression analyses identified age, number of visible tubal ostia postoperatively, and surgical method as significant factors affecting pregnancy outcomes (P<0.05). The LightGBM model based on surgical method had an area under the curve (AUC) of 0.882 (0.838-0.926), with internal validation AUC of 0.817 (0.790-0.840). CONCLUSIONS Cold knife surgery promotes faster recovery of the endometrial microenvironment and earlier improvement of fertility in patients with secondary infertility and IUA Surgical method is a key factor influencing pregnancy outcomes, and the LightGBM model based on surgical approach shows good predictive performance for pregnancy outcomes in patients with moderate-to-severe IUA.
Humans ; Female ; Pregnancy ; Tissue Adhesions/surgery* ; Retrospective Studies ; Adult ; Pregnancy Outcome ; Uterine Diseases/surgery* ; Hysteroscopy/methods* ; Infertility, Female/etiology* ; Electrosurgery/methods* ; Fertilization in Vitro ; Endometrium/surgery* ; Embryo Transfer ; Vascular Endothelial Growth Factor A/metabolism*

Mitochondrial encephalomyopathy is a multisystemic metabolic disorder caused by mutations in mitochondrial or nuclear genes. It commonly presents with stroke-like episodes or myopathy as initial symptoms. This paper reports a young male patient with mitochondrial encephalomyopathy whose early and prominent clinical manifestation was refractory shock, without typical neurological symptoms. The patient initially presented with abdominal pain and lower limb weakness, followed by severe hypotension requiring high-dose vasopressors to maintain blood pressure. His lactate level peaked at 20 mmol/L. After 10 days of symptomatic and supportive treatment, his hypotension resolved; lactate levels returned to normal by day 22. One month later, he still had difficulty weaning from mechanical ventilation and exhibited persistent limb weakness. Genetic testing of the biceps brachii revealed an m.3271T>C mutation in the mitochondrial tRNA gene. Mitochondrial encephalomyopathy may initially present with severe circulatory dysfunction. In patients with lactic acidosis not related to hypoperfusion, mitochondrial disease should be considered, and genetic testing of muscle or other peripheral tissues may improve diagnostic yield.
Humans ; Male ; Mitochondrial Encephalomyopathies/genetics* ; Mutation ; Shock/etiology*

Multiple myeloma (MM) is a common hematologic malignancy that originates from precursor conditions such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Identifying its risk factors is crucial for early intervention. The etiology of MM is multifactorial, involving race, familial clustering, gender, age, obesity, cytogenetic abnormalities, and environmental exposures. Among these, cytogenetic abnormalities and modifiable factors play pivotal roles in MM pathogenesis and progression. 1) cytogenetic abnormalities. Primary abnormalities [e.g., hyperdiploidy, t(11;14), t(14;16)] emerge at the MGUS stage, while secondary abnormalities [e.g., 1q+, del(17p)] drive disease progression. The accumulation of 1q+ promotes clonal evolution, and del(17p) is associated with significantly reduced survival. 2) modifiable risk factors. Obesity promotes MM via the acetyl-CoA synthetase 2 (ACSS2)-interferon regulatory factor 4 (IRF4) pathway. Vitamin D deficiency weakens immune surveillance. Exposure to herbicides such as Agent Orange and glyphosate increases MGUS incidence. Insufficient UV exposure, by reducing vitamin D synthesis, elevates MM risk. Gut microbiota dysbiosis (enrichment of nitrogen-cycle bacteria and depletion of short-chain fatty acids producers) induces chromosomal instability through the ammonium ion-solute carrier family 12 member 22 (SLC12A2)-NEK2 axis. Therefore, risk-based screening among high-risk populations (e.g., those who are obese, elderly, or chemically exposed), along with early interventions targeting cytogenetic abnormalities [e.g., B cell lymphoma 2 (Bcl-2) inhibitors for t(11;14), ferroptosis inducers for t(4;14)] and modifiable factors (e.g., vitamin D supplementation, gut microbiota modulation), may effectively delay disease progression and improve prognosis.
Humans ; Multiple Myeloma/epidemiology* ; Risk Factors ; Obesity/complications* ; Chromosome Aberrations ; Monoclonal Gammopathy of Undetermined Significance/etiology* ; Gastrointestinal Microbiome ; Vitamin D Deficiency/complications* ; Precancerous Conditions/genetics*

OBJECTIVES: Intracranial aneurysm (IA) has an insidious onset, and once ruptured, it carries high rates of mortality and disability. Cardiometabolic factors may be associated with the formation and rupture of IA. This study aims to summarize the application of Mendelian randomization (MR) methods in research on cardiometabolic factors and IA, providing insights for further elucidation of IA etiology and pathogenesis. METHODS: Literature about MR-based IA studies published up to February 21, 2024, was retrieved from PubMed, Embase, Web of Science, CNKI, and Wanfang. Two researchers independently performed literature screening, data extraction, and quality assessment. A narrative synthesis approach was used to conduct a qualitative systematic review of the included studies. RESULTS: A total of 11 MR-based studies on IA published between 2017 to 2024 were included, of which 4 were rated as high quality. These studies investigated the associations between blood pressure, blood lipids, blood glucose, obesity-related indicators, and inflammatory cytokines with IA and its subtypes, though issues of duplication were noted. Four MR studies based on the same European population but using different instrumental variable selection criteria, as well as another MR study in a different European cohort, consistently identified blood pressure as a risk factor for IA and its subtypes. Findings for blood lipids, blood glucose, obesity-related indicators, and inflammatory cytokines were inconsistent across MR studies. CONCLUSIONS Blood pressure appears to increase the risk of IA and its subtypes. Associations between other cardiometabolic factors and IA/subtypes require further in-depth investigation. Given the inherent limitations of MR studies, causal inferences should be made cautiously in combination with other lines of evidence.
Humans ; Mendelian Randomization Analysis ; Intracranial Aneurysm/etiology* ; Risk Factors ; Blood Pressure ; Blood Glucose ; Obesity/complications* ; Cardiometabolic Risk Factors ; Lipids/blood*