Long-Term Follow-Up of Ultrasound-Guided Glossopharyngeal Nerve Block Treatment for Glossopharyngeal Neuralgia: A Retrospective Clinical Study of 43 Cases.

Background: Glossopharyngeal neuralgia (GPN) is a rare chronic neuropathic pain disorder that significantly impacts quality of life. Ultrasound-guided glossopharyngeal nerve blocks (UGPNB) have gained popularity due to their various advantages. However, there have been no studies reporting the long-term outcomes of UGPNB in a larger cohort of GPN patients. Aim: This study aims to evaluate the efficacy and safety of UGPNB in patients with GPN. Methods: We reviewed the electronic medical records of patients with GPN who received UGPNB at the Department of Pain Medicine of the First Medical Center, PLA General Hospital between June 1, 2011, and June 1, 2022. The effect of UGPNB was evaluated using the Barrow Neurological Institute (BNI) scale. Improvement was defined as a reduction in pain category by comparing pain categories before and after therapy. Recovery was defined as achieving BNI I after treatment. Patients who responded to treatment but then regressed to the category before therapy were considered to have experienced pain relapse. Results: A total of 43 patients with GPN who received UGPNB were included in the analysis. At discharge, 35 (81.4%) patients experienced pain improvement after treatment, and among them, 13 (30.2%) patients achieved recovery. After discharge, 13 patients (37.1%) out of the 35 effective patients experienced pain relapse at different time intervals: 0.5, 0.7, 1, 1, 3, 3, 4, 12, 15, 36, 45, 63, and 96 months. The cumulative recurrence-free survival rates were 88.85% at month 1, 82.83% at month 3, 77.04% at month 12, 70.31% at month 36, and 54.66% at month 120. Among the 13 patients who experienced relapse, four patients received a second UGPNB treatment, and pain improved in two patients (50%). No severe adverse reactions were documented. Conclusion: UGPNB is an effective, repeatable, safe, and minimally invasive treatment for patients with GPN. It may be preferable to consider UGPNB before undergoing invasive intracranial surgery or neurodestructive methods.

Sevoflurane exerts antidepressant-like effects via the BDNF-TrkB pathway.

Depression has emerged as the predominant psychiatric affliction affecting individuals. Prior research has substantiated the antidepressant properties exhibited by numerous anesthetics. Sevoflurane, a widely utilized inhalant anesthetic in clinical practice, remains relatively uncharted in terms of its specific antidepressant effects. In this study, we used open field test, forced swimming test and novelty-suppressed feeding test to investigate the anxiety and depression-like behaviors in C57BL/6 mice following the inhalation of sevoflurane. We then used western blotting to scrutinized the expression levels of proteins associated with the brain-derived neurotrophic factor (BDNF)-tryosine receptor kinase B (TrkB) pathway in the hippocampus and prefrontal cortex. To further investigate whether sevoflurane exerts antidepressant-like effects via the BDNF-TrkB pathway, we downregulated TrkB expression by administering siRNA into the lateral ventricle. We found that the inhalation of 2.5 % sevoflurane exerted a significant antidepressant-like effect, accompanied by an elevation in p-TrkB expression levels in the hippocampus and prefrontal cortex. Intriguingly, this antidepressant-like effect was abrogated following the downregulation of TrkB expression through the microinjection of siRNA into the lateral ventricle. In conclusion, this study provides evidence supporting the notion that sevoflurane exerts its antidepressant-like effect via the BDNF-TrkB signaling pathway.

Piezoionic High Performance Hydrogel Generator and Active Protein Absorber via Microscopic Porosity and Phase Blending.

Generating electricity in hydrogel is very important but remains difficult. Hydrogel with electricity generation capability is more capable in bio-relevant tasks such as tissue engineering, artificial skin, or medical treatment, because electricity is indispensable in regulating physiological activities. Here, a porous and phase blending hydrogel structure for effective piezoionic electricity generation is developed. Dynamic electric field is generated taking advantage of the difference in streaming speeds of sodium and chloride in the material. Microscopic porosity and hydrophilic-hydrophobic phase blending are the two key factors for prominent piezoionic performance. Voltages as high as 600 mV are first realized in hydrogels in response to medical ultrasound stimulation. The hydrogel structure is also subjective to effective substance exchange and can actively enrich proteins from surroundings under mechanical stimuli. Preliminary applications in neural stimulation, constructing complex spatial-temporal chemical and electric field distribution patterns, mimetic tactile sensor, sample pretreatment in fast detection, and enzyme immobilization are demonstrated.

Mental health changes in elderly patients undergoing non-cardiac surgery during the COVID-19 pandemic in China.

BACKGROUND: The COVID-19 pandemic has a heavy impact on the mental health of elderly surgical patients worldwide. In particular, the elderly patients faced considerable psychological stress due to various environmental and medical factors during the outbreak. This study aims to examine changes in mental health trends among non-cardiac surgical patients aged 65 and above in China during the COVID-19 pandemic. METHODS: This multi-center, convenient sampling, longitudinal observational study was conducted from April 1, 2020 to April 30, 2022. Primary outcome was the prevalence of postoperative depression. Secondary outcome was the prevalence of postoperative anxiety. Follow-up was conducted separately at 7 days and 30 days after surgery. Depression symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9) scale. Anxiety symptoms were assessed using Generalized Anxiety Disorder-7 (GAD-7) scale, with scores of ≥5 defining positive depression or anxiety symptoms. Multivariate logistic regression analysis was used to investigate risk factors of mental health status in more elderly patients undergoing non-cardiac surgery. RESULTS: A total of 4639 patients were included, of whom 2279 (46.0 %) were male, 752 (15.2 %) were over the age of 75, and 4346 (93.7 %) were married. The monthly prevalence trends demonstrated that compared to the outbreak period, a significant reduction in the prevalence of depression and anxiety symptoms in elderly patients who underwent surgery during the post-pandemic period. In post-pandemic period, a statistically significant decrease in the prevalence of all severity depression and anxiety patients was noted at the 7-day follow-up, but no significant decrease was observed for severe depression and anxiety in the 30-day follow-up. In COVID-19 low-risk area, a significant overall decrease in prevalence of mental health was observed during the post-pandemic period compared to the outbreak period, including 7-day depression, 7-day anxiety, 30-day depression, and 30-day anxiety (all with P < 0.001). Female and patients with ≥2 comorbidities appeared to be more susceptible to postoperative depression and anxiety during the pandemic. LIMITATION: The absence of data from the early days of the COVID-19 outbreak. CONCLUSIONS: This study analyzed the prevalence of depression and anxiety in elderly non-cardiac patients during and after the COVID-19 pandemic, focusing on dimensions such as severity, risk-areas, gender, and comorbidity. Our findings revealed a significant decrease in the prevalence of depression and anxiety in elderly surgery patients during the post-pandemic period.

Permeability Prediction of Nanoscale Porous Materials Using Discrete Cosine Transform-Based Artificial Neural Networks.

The permeability of porous materials determines the fluid flow rate and aids in the prediction of their mechanical properties. This study developed a novel approach that combines the discrete cosine transform (DCT) and artificial neural networks (ANN) for permeability analysis and prediction in digital rock images, focusing on nanoscale porous materials in shale formations. The DCT effectively captured the morphology and spatial distribution of material structure at the nanoscale and enhanced the computational efficiency, which was crucial for handling the complexity and high dimensionality of the digital rock images. The ANN model, trained using the Levenberg-Marquardt algorithm, preserved essential features and demonstrated exceptional accuracy for permeability prediction from the DCT-processed rock images. Our approach offers versatility and efficiency in handling diverse rock samples, from nanoscale shale to microscale sandstone. This work contributes to the comprehension and exploitation of unconventional resources, especially those preserved in nanoscale pore structures.

GABAergic neurons in the nucleus accumbens core mediate the antidepressant effects of sevoflurane.

General anaesthetics have been widely applied to induce reversible loss and recovery of consciousness in clinical practice and have been shown to have reliably safe profiles. Since brief exposure to general anaesthetics can result in long-lasting and global changes in neuronal structures and function, these drugs also exhibit strong therapeutic potential for mood disorders. Preliminary and clinical studies have suggested that the inhalational anaesthetic drug sevoflurane might relieve symptoms of depression. However, the antidepressant effects of sevoflurane and the underlying mechanisms remain elusive. In the present study, we confirmed that the antidepressant and anxiolytic effects of inhaling 2.5% sevoflurane for 30 min were comparable to those of ketamine and could be sustained for 48 h. Activation of GABAergic (γ-aminobutyric acidergic) neurons in the nucleus accumbens core by chemogenetics was shown to mimic the antidepressant effects of inhaled sevoflurane, whereas inhibition of these neurons significantly prevented these effects. Considered together, these results suggested that sevoflurane might exert rapid and long-lasting antidepressant effects via modulation of neuronal activities in the nucleus accumbens core nucleus.

The Roles of Aerobic Exercise and Folate Supplementation in Hyperhomocysteinemia-Accelerated Atherosclerosis.

Background: Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. Effective interventions to reduce HHcy-accelerated atherosclerosis are required. Objectives: This study aimed to investigate the effects of aerobic exercise (AE) and folate (FA) supplementation on plasma homocysteine (Hcy) level and atherosclerosis development in a mouse model. Methods: Six-week-old female apoE-/- mice were grouped into five groups (N = 6-8): HHcy (1.8 g/L DL-homocysteine (DL-Hcy) in drinking water), HHcy + AE (1.8 g/L DL-Hcy and aerobic exercise training on a treadmill), HHcy + FA (1.8 g/L DL-Hcy and 0.006% folate in diet), HHcy + AE + FA (1.8 g/L DL-Hcy, 0.006% folate, and aerobic exercise training on a treadmill), and a control group (regular water and diet). All treatment was sustained for 8 weeks. Triglyceride, cholesterol, lipoprotein, and Hcy levels were determined enzymatically. Plaque and monocyte chemoattractant protein-1 (MCP-1) expression levels in mouse aortic roots were evaluated by immunohistochemistry. Results: Compared to the HHcy group (18.88 ± 6.13 µmol/L), plasma Hcy concentration was significantly reduced in the HHcy + AE (14.79 ± 3.05 µmol/L, p = 0.04), HHcy + FA (9.4 ± 3.85 µmol/L, p < 0.001), and HHcy + AE + FA (9.33 ± 2.21 µmol/L, p < 0.001) groups. Significantly decreased aortic root plaque area and plaque burden were found in the HHcy + AE and HHcy + AE + FA groups compared to those in the HHcy group (both p < 0.05). Plasma MCP-1 level and MCP-1 expression in atherosclerotic lesions were significantly decreased in the HHcy + AE and HHcy + AE + FA groups compared to the HHcy group (all p < 0.05). Conclusions: AE reduced atherosclerosis development in HHcy apoE-/- mice independently of reducing Hcy levels. FA supplementation decreased plasma Hcy levels without attenuating HHcy-accelerated atherosclerosis. AE and FA supplementation have distinct mechanisms in benefiting atherosclerosis.

Activation of the ERK1/2 pathway mediates the neuroprotective effect provided by calycosin treatment.

Calycosin is a natural product extracted from some plant families and exhibits various biological properties. But the effect of calycosin on cerebral ischemia-reperfusion injury has not been fully elucidated. In this study, the neuroprotective effect of calycosin treatment on the differentiated SH-SY5Y cells exposed to OGD was evaluated using MTT and flow cytometry. Rats that were pretreatment with calycosin were subjected to MCAO, neurological behavior scores and brain infarct volume were evaluated. The protein expression of pERK/ERK were assessed using Western blot. siRNA-pERK and U0126 were administered to investigate the impact of the ERK pathway on calycosin preconditioning. The results demonstrated the neuronal viability in the calycosin-treated SH-SY5Y cells increased significantly, and the rate of apoptosis decreased compared with the Oxygen-glucose deprivation only SH-SY5Y cells. Calycosin pretreatment reduced infarct volume and improved neurological outcome in rats subjected to MCAO. Administration of calycosin increased the ratio of pERK/ERK expression, which was down-regulated in ischemia-reperfusion group. Down-regulation of pERK/ERK significantly attenuated the neuroprotective effect induced by calycosin pretreatment in vitro and in vivo. We concluded calycosin treatment could induce a neuroprotective effect against ischemia, which was related to the regulation of the ERK1/2 pathway.

Sacral Nerve Stimulation in Patients With Refractory Pudendal Neuralgia.

BACKGROUND: Pudendal neuralgia (PN) is one of the most common forms of genital pain. Only 42.2% of PN patients respond to the first-line treatment. Novel neuromodulation techniques in the treatment of refractory PN patients are urgently required. OBJECTIVES: The aim of this study was to evaluate the treatment effects and adverse events of sacral nerve stimulation (SNS) for patients with refractory PN. STUDY DESIGN: A prospective nonrandomized study. SETTING: This prospective analysis included 33 patients who received the phase II surgical implantation. METHODS: A total of 55 eligible PN patients were recruited for SNS treatment after informed consent, and 33 of 55 patients with a minimum 50% improvement were candidates for surgical implantation. Visual Analog Scale (VAS) scores, Self-rating Anxiety and Depression Scale, Quality of life score (SF-36), and sleep monitoring indicators before and after surgery were used to assess the effects of SNS on patients with refractory PN. RESULTS: Thirty-three patients were included in the final analysis, involving 24 women and 9 men with a mean age of 49.5 years (26-70 years). There was a favorable decrease in pain severity (VAS scores) from 7.1 ± 1.1 at baseline to 6.1 ± 1.0 on postoperative day 1, and 2.8 ± 0.7 at 1 week, 1.7 ± 0.5 at 1 month, 1.1 ± 0.7 at 6 months, and 1.0 ± 0.6 at 12 months after surgery, respectively (P < 0.05). The mean score of each section of SF-36 after SNS was significantly higher than that at baseline (P < 0.05). Total sleep time and sleep time in each period were significantly prolonged after SNS implantation compared with that before surgery (6 months vs Pre, total: 5.32 ± 1.49 hours vs 3.66 ± 1.19 hours, deep: 2.52 ± 0.63 hours vs 1.36 ± 0.43 hours, light: 1.78 ± 0.42 hours vs 0.99 ± 0.30 hours, rapid eye movement: 1.41 ± 0.29 hours vs 0.89 ± 0.27 hours, P < 0.05). No serious device complications were reported during the follow-up period. LIMITATIONS: Large-scale randomized clinical trials are warranted to evaluate the risk factors for prediction of refractory PN. CONCLUSIONS: These data imply that SNS can have beneficial effects on patients with refractory PN.

Sonic Hedgehog Signaling Contributes to Chronic Post-Thoracotomy Pain via Activating BDNF/TrkB Pathway in Rats.

PURPOSE: Some patients undergoing thoracotomy may suffer from chronic post-thoracotomy pain (CPTP). Treatment of CPTP has been a clinical challenge and the underlying mechanisms of CPTP remain elusive. Recently, sonic hedgehog (Shh) signaling has been shown to be associated with various pain states but its role in the pathogenesis of CPTP is still unclear. METHODS: CPTP was induced in rats by thoracotomy. Rats were divided into CPTP group and non-CPTP group based on the mechanical withdrawal threshold (MWT). Rats were administered with Shh signaling inhibitor cyclopamine and activator smoothened agonist (SAG), and then evaluated by MWT and cold allodynia testing. The expressions of Shh signaling (Shh ligand, patched and smoothened receptor, Gli transcription factors), brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase receptor B (Trk-B), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) in rat T4-5 spinal cord dorsal horn (SDH) were detected by Western blotting and immunohistochemistry. RESULTS: The expression of Shh signaling significantly increased and the BDNF/TrkB pathway was activated in T4-5 SDH of CPTP rats. Cyclopamine attenuated hyperalgesia and down-regulated the expressions of Gil1, BDNF, p-TrkB, p-PI3K and p-Akt in CPTP rats. SAG induced hyperalgesia in non-CPTP rats and elevated the expressions of Gil1, BDNF, p-TrkB, p-PI3K and p-Akt. CONCLUSION: Shh signaling may contribute to CPTP via activating BDNF/TrkB signaling pathway, and inhibition of Shh signaling may effectively alleviate CPTP.

Normal values of nasal NO and exhaled NO in young Chinese people aged 9 - 22 years.

OBJECTIVE: To assess the normal levels of nasal nitric oxide (NNO) and fractional exhaled nitric oxide (FENO) in healthy Chinese young people, and to determine whether the obtained values were associated with age, sex, height, weight, BMI (body mass index) or BSA (body surface area). METHODS: One hundred and twenty healthy people were selected from a total of 436 Chinese young people based on their answers to a questionnaire. An electrochemical analyzer (NIOX MINO system) was used to measure NNO and FENO. The relationship between NNO, FENO and age, sex, height, weight, BMI, BSA was analyzed using SPSS software. RESULTS: The values of NNO were normal distributed (mean 273.5 ppb; SD 112.3). The values of FENO were non-normally (Skewed) distributed (median: 14.00 ppb; interquartile range: 7.00 ppb). The obtained NNO values were independent of age, sex, height, weight, BMI and BSA, but were positively correlated to lnFENO (FENO log base e); lnFENO values were also independent of age, height, weight, BMI and BSA, but correlated with NNO and sex. CONCLUSIONS: NNO values positively correlate with lnFENO in healthy people and the levels of each may be predicted by the other. The results of this study are expected to serve as a reference for future studies in China.

[Diagnosis and clinical characteristics of patients with non-allergic rhinitis].

OBJECTIVE: To explore a step-by-step exclusive diagnosis and analyze the clinical characters of non-allergic rhinitis (NAR). METHODS: Patients with symptoms (nasal itching, sneezing, rhinorrhea, nasal congestion) were selected to take four-step exclusive diagnosis for NAR and we tried to eliminate the false NAR and retain the true NAR. First step was to exclude the patients who were not suitable for skin prick test (SPT, such as during pregnancy, breastfeeding, asthma, oral antihistamine medication in 7 day, severe skin diseases). The second step was to exclude the patients with positive SPT and the third step was to exclude the patients with 1 level or above of specific sero-immunoglobulin E (sIgE). The fourth step was to exclude the patients with infection rhinitis, clear abnormal nasal structure, drug-induced rhinitis, nasal neoplasm. The remained patients were finally diagnosed as NAR and who were further differential diagnosed as vasomotor rhinitis (VMR) or non-allergic rhinitis with eosinophilia syndrome (NARES) according to the eosinophilia counts in nasal secretion and venous blood. The common characters of patients with NAR were analyzed and their symptoms and quality of life were evaluated by visual analogue scale (VAS) and rhino-conjunctivitis quality of life questionnaire (RQLQ) separately. RESULTS: One thousand four hundred and thirty-seven patients were included after first step exclusion and 735 cases with negative SPT were remained after second step exclusion. Of 735 patients, 302 were tested in vitro for sIgE and 93 cases with 0 level of sIgE and total IgE were remained after third step exclusion. Sixty-two patients were finally diagnosed as NAR after fourth step exclusion. The NAR diagnosis rate was 51.15% (735/1 437) with negative SPT alone and the NAR diagnosis rate was 29.06% (93/302) with combination of negative SPT and sIgE. Of 62 patients with NAR, 47 patients (75.81%) were diagnosed as VMR and 15 cases (24.19%) as NARES. There were 23 males and 39 females in the 62 patients aged 11 - 77 years. The history was 11-47 months. The biggest numbers of patients with VMR or NARES were among 41-50 years. Their onset ages were among 21-30 years in both two groups. VAS scores of nasal congestion in VMR patients were the highest with significant difference among nasal symptoms (F = 3.958 0, P = 0.009 1). VAS scores of sneezing in NARES patients were the highest but without significant difference among nasal symptoms. There were no difference in seven domain scores of RQLQ and the total mean scores between VMR group and NARES group but the nasal symptoms got the highest scores with significant difference among the seven domains in each group (VMR group, F = 9.771 2, P = 0.000 0;NRAES group, F = 3.226 9, P = 0.006 2). CONCLUSIONS: SPT combined with sIgE may exclude much more patients with AR. Females with NAR are much more than males. Patients with NAR aged 21-30 years. The characters of NAR are helpful to improve our knowledge about NAR. VAS and RQLQ may be a suitable tool in assessment of NAR.

[Noninvasive measurement of nasal NO and fractional exhaled NO in healthy people and patients with allergic rhinitis].

OBJECTIVE: To measure the nasal nitric oxide (NNO) and fractional exhaled nitric oxide (FENO) in healthy people and patients with allergic rhinitis (AR), and to discuss the clinical significance of the results. METHODS: Ninety-six healthy volunteers and 51 patients with moderate-severe persistent AR, but without asthma, were enrolled. NNO and FENO concentrations were measured noninvasively by using of NIOX MINO (Aerocrine AB, Solna, Sweden).SPSS 13.0 software was used to analyze the data. RESULTS: The concentration of NNO in healthy people was 245.0 [189.8;331.3] ppb (median [25th percentile; 75th percentile], the followings were same as). The concentration of FENO was 14.0 [10.0; 18.0] ppb. The concentration of NNO in patients with AR was 304.0[179.5; 397.5]ppb. The concentration of FENO was 21.0 [16.0; 40.5] ppb. The concentration of NNO in the AR patients was higher than that in the healthy persons, but the difference did not reach statistical significance (Z = 1.349, P = 0.177).On the other hand, FENO concentrations were significantly increased in patients compared with concentrations in healthy persons (Z = 5.555, P = 0.000). CONCLUSIONS: FENO concentrations of patients with moderate-severe persistent AR are increased significantly even though the patients do not have typical symptoms of asthma. This finding suggests that AR patients should be treated actively in order to prevent asthma from developing in them.

[Clinical characteristics of primary ciliary dyskinesia].

OBJECTIVE: To analyze the clinical characteristics of primary ciliary dyskinesia(PCD) so as to improve the diagnostic level of this rarely seen disease. METHODS: Ten patients with PCD were retrospectively reviewed, the medical history, symptoms, signs, lung CT or chest X-ray, rhino-sinus CT scan, nasal nitric oxide (NO) levels, nasal ciliary ultrastructure, DNAH5 and DNAH11 genetic mutation, as well as treatment outcome were analyzed. RESULTS: All 10 patients had recurrent chronic sinusitis, otitis media, bronchitis/bronchiectasis since childhood. Nine cases with translocation of heart and big vessels were diagnosed as Kartagener syndrome. One woman was suffering from barrenness and one man sterility after marriage for long time without birth control. Nasal NO levels were significantly lower in 2 patients with PCD but it was almost normal in one patient. Ciliary ultrastructure investigated by transmission electron microscope were almost normal in 4 cases without missing of inner or outer dynein arms. Two cases taking exome capture sequencing showed that mutations happened in DNAH5 and DNAH11. Five subjects underwenting sanger sequencing on 6 common exon fragments of DNAH5 and DNAH11 did not show any abnormality. Ten cases took medication therapy, while 5 patients once underwent functional endoscope sinus surgery. All of the 10 patients had improvement of their symptoms and signs after treatment. CONCLUSIONS: The PCD is so rare in clinic that it is easily misdiagnosed. Clinical characteristics, nasal NO levels, ciliary ultrastructure and genetic testing are significant for clinical diagnosis.

Frequency of tuberculosis among diabetic patients in the People's Republic of China.

The People's Republic of China has nearly the highest incidence of both diabetes mellitus (DM) and tuberculosis (TB) worldwide. DM increases the risk of TB by two to three times and adversely affects TB treatment outcomes. The increasing epidemic of DM in the People's Republic of China is due to decreased physical activity, unhealthy diet, and obesity. Over the last 20 years, the excellent free China National Tuberculosis Program has been set up, and the "DOTS" (directly observed treatment + short-course chemotherapy) model for TB control has successfully reduced the burden of TB, but the disease is still a considerable problem. Given the high burden of TB and DM in the People's Republic of China and the relationship between the two diseases, it is sensible to screen DM patients for TB. A bidirectional screening of the two diseases was conducted in the People's Republic of China from 2011 to 2012, which identified a TB incidence in patients with DM of about 958 per 100,000. Here, we report the findings of our recent study on the incidence of TB among diabetic patients in the People's Republic of China. The data agree with those of previous reports.

[Early genetic diagnosis in patients with HHT induced severe nosebleed].

OBJECTIVE: To study the early gene diagnosis of hereditary hemorrhagic telangiectasia (HHT) induced severe nosebleed. METHOD: Clinical features of 23 family members in two HHT pedigrees were examined. Genomic DNA was extracted from peripheral blood samples. PCR amplification was conducted to screen ENG and ACVRL-1 genes with their specific primers. Direct sequencing was performed to detect the mutation. Mutation analysis was carried out to evaluate its significance. RESULT: A heterozygous c. 263A > G mutation was identified in exon 3 of ACVRL-1 in 6 out of 11 members in NMG-1 pedigree. In GD-2 pedigree, 5 of 11 members carried c. 199C > G mutation. Mutation detection rate was 100% in subjects with nosebleed history and 25% in family members without epistaxis. CONCLUSION: Gene diagnosis characterized by high sensitivity and specificity is of great practi-cal significance and early genetic screening should be a clinical routine test for HHT induced severe nosebleed.