OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

Objective: To analyze the correlation between serum homocysteine (Hcy) and both folic acid (FA) and sperm DNA fragmentation index (DFI), so as to provide the evidence for male fertility assessment. Methods: Males who visited and measured the serum Hcy in the Reproductive Medicine Center of Huzhou Maternal and Child Health Care Hospital from September 2022 to September 2023 were selected as the study subjects. Sperm quality parameters and sperm DFI were analyzed by collecting sperm. Hcy and FA were measured by collecting venous blood. Participants were stratified into a high Hcy group (Hcy≥15.0 μmol/L) and a normal group (Hcy<15.0 μmol/L). The correlations between serum Hcy and FA and sperm DFI were evaluated using linear regression models. Results: A total of 173 participants were enrolled, including 39 in the high Hcy group and 134 in the normal group. The sperm concentration in the high Hcy group was significantly lower than that in the normal group [(91.77±61.11)×106/mL vs. (144.21±106.82)×106/mL, P<0.05]. No statistically significant differences were observed in semen volume, sperm motility, curvilinear velocity, straight-line velocity, average path velocity, or sperm morphology normal rate (all P>0.05). The FA level in the high Hcy group was lower than that in the normal group [(4.44±1.79) nmol/L vs. (7.64±3.68) nmol/L, P<0.05]. The sperm DFI in the high Hcy group was higher than that in the normal group [(19.21±8.85)% vs. (13.07±6.43)%, P<0.05]. Serum Hcy level showed a negative correlation with FA level (r=-0.369, P<0.05) and a positive correlation with sperm DFI (r=0.351, P<0.05). Conclusion Serum Hcy level is associated with sperm concentration, FA and sperm DFI, suggesting that serum Hcy may affect sperm quality.

OBJECTIVE: To observe the clinical efficacy of electroacupuncture (EA) at "four points of sacral region" for mild-to-moderate benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). METHODS: A total of 58 patients with BPH/LUTS were randomly divided into a sacral four-point EA group (29 cases, 1 case dropped out) and a conventional EA group (29 cases, 1 case dropped out). EA was applied at bilateral points 0.5 cun lateral to the sacrococcygeal joint and Huiyang (BL35) in the sacral four-point EA group; and was applied at Guanyuan (CV4), Zhongji (CV3), Qugu (CV2) and bilateral Shuidao (ST28), Sanyinjiao (SP6), Zusanli (ST36) in the conventional EA group. Both groups received continuous wave, 2 Hz in frequency, 30 min a time, once every other day, 3 times a week for 4 weeks. Before treatment, after 2 and 4 weeks of treatment, and in follow-up of 1 month after treatment completion, the international prostate symptom score (IPSS), the overactive bladder symptom score (OABSS), the quality of life (QOL) score were observed; before and after treatment, the prostate volume (PV) was measured by abdominal ultrasound; and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: Compared before treatment, the scores of IPSS, OABSS and QOL were decreased after 4 weeks of treatment and in follow-up in both groups (P<0.01, P<0.05). In the sacral four-point EA group, the scores of IPSS and QOL after 4 weeks of treatment and in follow-up were lower than those in the conventional EA group (P<0.05, P<0.01), and the OABSS score in follow-up was lower than that in the conventional EA group (P<0.05). After 4 weeks of treatment and in follow-up, the reductions of IPSS and OABSS scores compared before treatment in the sacral four-point EA group were larger than those in the conventional EA group (P<0.01, P<0.05); After 2, 4 weeks of treatment and in follow-up, the reductions of QOL score compared before treatment in the sacral four-point EA group were larger than those in the conventional EA group (P<0.01). No significant difference in PV was observed after treatment between the two groups (P>0.05). The total effective rate was 75.0% (21/28) in the sacral four-point EA group, which was higher than 39.3% (11/28) in the conventional EA group (P<0.01). CONCLUSION EA at "four points of sacral region" can effectively improve the LUTS, overactive bladder symptom and quality of life in patients with mild-to-moderate BPH, and has good short-term and long-term efficacy, although it can not reduce prostate volume.
Humans ; Male ; Electroacupuncture ; Prostatic Hyperplasia/complications* ; Aged ; Middle Aged ; Lower Urinary Tract Symptoms/physiopathology* ; Acupuncture Points ; Treatment Outcome ; Quality of Life

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

Purpose To analyze and discuss the clinicopathological,molecular pathological characteristics,as well as diagnostic and prognostic features of pleomorphic xanthoastrocytoma(PXA)according to the new WHO classifi-cation.Methods 79 cases of PXA were collected to analyze their pathological and clinical data.Immunohistochemis-try using the EnVision method was employed to detect the expression of CD34,ATRX,Rb,Olig-2,H3K27M,H3K27me3,IDH1 R132H,BRAF VE1 and Ki67.Sanger sequencing was used to detect mutations in H3F3A and IDH1/2.Fluorescence quantitative PCR was used to detect the BRAF V600E mutation and TERT promoter region al-terations.Fluorescence in situ hybridization(FISH)was used to detect CDKN2A and EGFR alterations.The relation-ship between clinical,pathological,molecular genetics data,and prognosis was analyzed.Results The patients'ages ranged from 9 to 69 years,with an average age of 36.4 years.Most tumors were located in the temporal lobe,frontal lobe and parietal lobe.Among the 79 cases,42 were classified as grade 2 PXA and 37 as grade 3 PXA.The tumor cells exhibited pleomorphic changes,with perivascular lymphocytic sheaths and eosinophilic bodies frequently ob-served.Grade 3 PXA exhibited more mitotic figures(average of 11.8/10 HPF),and was usually accompanied by nec-rosis,focal marginal infiltration and microvascular proliferation.Immunohistochemistry and molecular characteristics revealed frequent positivity for CD34,BRAF V600E mutation(68.1％),and CDKN2A homozygous deletion(36.8％)in PXA.Some cases showed TERT gene mutation and absent Rb expression.Univariate survival analysis in-dicated that necrosis,focal marginal infiltration,and CNS WHO grade were related to overall survival,while focal infil-tration and CNS WHO grade were the independent risk factors.Conclusion The prognosis of CNS WHO grade 3 PXA is wrose than that of grade 2 PXA.Accurate diagnosis of PXA requires the combination of the morphological features,immunohistochemical staining,and multiple molecular tests.

Objective:To explore the influencing factors of dietary habits on the progression from prediabetes to type 2 diabetes mellitus(T2DM)in elderly individuals undergoing health check-ups.Methods:In the cross-sectional study, we enrolled individuals aged 60-70 years with fasting plasma glucose (FPG)≥6.0 mmol/L who underwent health examinations at the Health Management Medical Center of Wenjiang District People's Hospital in Chengdu from 2019 to 2022.Demographic characteristics, dietary habit questionnaires, and FPG values were collected.Unconditional binary logistic regression analysis was used to identify factors influencing the natural progression from prediabetes to T2DM.A nomogram prediction model was established based on logistic regression results, and its predictive performance was evaluated by calculating the C-statistics and drawing a calibration curve.Results:A total of 13 681 elderly participants with FPG ≥6.0 mmol/L were included, comprising 4 306(31.5%)prediabetes cases(FPG 6.0-7.0 mmol/L), aged(63.54±16.49)years and 9 375(68.5%)T2DM cases(FPG>7.0 mmol/L), aged(63.09±16.21)years.Unconditional binary logistic regression analysis showed that frequent breakfast( OR=0.777, 95% CI: 0.696-0.868, P<0.001), dietary preference for light diet( OR=0.781, 95% CI: 0.710-0.858, P<0.001), salty taste( OR=0.571, 95% CI: 0.504-0.648, P<0.001), raw food( OR=0.327, 95% CI: 0.224-0.478, P<0.001)and spicy taste( OR=0.124, 95% CI: 0.112-0.137, P<0.001)were the protective factors for the conversion of prediabetes to the T2DM stage in the elderly physical examination population.While fast eating rate( OR=4.327, 95% CI: 3.978-4.772, P<0.001), dietary preference for sweets( OR=5.168, 95% CI: 4.703-5.678, P<0.001), and high-fat diet( OR=1.401, 95% CI: 1.275-1.539, P<0.001)were risk factors for conversion of prediabetes to T2DM stage.C-statistic of the Nomogram prediction model was 0.781; the goodness-of-fit test of the calibration curve was χ2=11.258, P=0.188, and the model predicted well. Conclusions:Regular breakfast, light diet, and dietary preferences for salty, raw, and spicy foods were protective factors for the transition from prediabetes to T2DM stage, whereas rapid eating rate, preference for sweets, and high-fat diets were risk factors for the transition from prediabetes to T2DM stage in the medical examination population.The constructed risk prediction model helped to find out the magnitude of the risk of T2DM in an individual, which increases the evidence for the transition from prediabetes to T2DM stage prevention evidence.

Objective:To compare the protective effects of the static cold storage (SCS) and normothermic machine perfusion (NMP) on the skeletal muscle of the amputated limbs of pigs.Methods:Four Landrace pigs were selected, from which eight limbs were amputated and divided into SCS group ( n=5) and NMP group ( n=3) according to the random number table method. After blood collection from the carotid artery, an amputated limb model was established by amputating the limbs at the scapulohumeral joints. The limbs in the SCS group were wrapped in sterile cloth and stored at 4 ℃ for 24 hours. In the NMP group, the limbs were mechanically perfused with a red blood cell-containing perfusion fluid at 37 ℃ for 24 hours, with 70% of the perfusion fluid replaced every 6 hours. Before the experiment, cross-matching tests with the saline medium were conducted between donor and recipient pigs to evaluate blood coagulation and blood safety in the NMP group. An allogeneic red blood cell perfusion fluid was prepared and the levels of pH, Na +, K +, Cl -, Ca 2+, glucose (Glu), hematocrit (Hct), lactic acid (Lac) and osmotic pressure of the perfusion fluid were measured. At 0, 6, 12, 18, and 24 hours after perfusion, the skin temperature and oxyhemoglobin saturation (SaO 2) levels in the NMP group were monitored and the levels of pH, Glu, creatine kinase (Ck), K +, Ca 2+, and Na +levels of the perfusion fluid were analyzed to evaluate the metabolism of the skeletal muscle in the amputated limbs. The mean intercellular distance and apoptosis index of the myocytes were quantitatively analyzed and histopathological changes were observed by performing HE staining and TUNEL staining on the skeletal muscle of the amputated limbs in both groups at 0 and 24 hours after perfusion. After perfusion was ended, the weight gain rate and swelling degree of the amputated limbs were compared between the two groups and the overall state of the amputated limbs was evaluated. Results:The result of the cross-matching test between donor and recipient pig blood was negative. The parameters in the prepared red blood cell-containing perfusion fluid generally maintained within a normal range: pH 7.38±0.04, Na + concentration (138.30±4.48)mmol/L, K + concentration (3.50±0.26)mmol/L, Glu concentration (6.11±2.08)mmol/L, and osmotic pressure (305.67±3.79)mmol/L. However, slightly higher Cl - and Ca 2+ concentrations [(118.34±12.00)mmol/L and (2.00±0.15)mmol/L] and lower Hct and lactate concentrations [0.30±0.03 and (1.54±0.38)mmol/L] were detected when compared with the reference range. During the perfusion, the average skin temperature of the amputated limbs in the NMP group was (36.13±0.98)℃, with the skin temperatures at 6, 12, 18, and 24 hours after perfusion being significantly higher than that at 0 hour ( P<0.01), while no significant difference among the skin temperatures at 6, 12, 18, and 24 hours after perfusion was observed ( P>0.05). The SaO 2 levels in the skin of the amputated limbs in the NMP group averaged over 95%, which showed no significant difference at 0, 12, 18, and 24 hours after perfusion ( P>0.05), while a significant elevation was observed at 6 hours compared with that at 0 hour ( P<0.05). There were no significant differences in pH, Glu, Na +, and Ca 2+ levels in the NMP group at 0, 6, 12, 18, and 24 hours after perfusion ( P>0.05), while the Ck levels at 18 and 24 hours were both significantly higher than that at 6 hours after perfusion ( P<0.05), and the Ck levels at 6, 12, 18, and 24 hours were all significantly higher than that at 0 hour ( P<0.05). The K + level progressively increased with the perfusion time, with significant elevations at 18 and 24 hours after perfusion compared with that at 0 hour ( P<0.05). HE staining revealed well-preserved muscle fiber continuity and regular arrangement in the NMP group and the SCS group at 0 hour, with an intercellular distance of (8.95±0.60)μm. At 24 hours, the NMP group exhibited slight skeletal muscle fiber rupture and swelling, with a slightly increased intercellular distance of (14.75±0.90)μm, significantly greater than that at 0 hour ( P<0.01). At 24 hours, the SCS group showed marked skeletal muscle fiber rupture and swelling, with a significantly increased intercellular distance of (23.51±1.49)μm, significantly larger than those at 0 hour in the same group and at 24 hours in the NMP group ( P<0.01). TUNEL immunofluorescence staining indicated a tiny amount of apoptotic cells in the skeletal muscle in both groups at 0 hour, with an apoptotic index of (4.26±1.62)%. There was a small number of apoptotic cells in the skeletal muscle in the NMP group at 24 hours, with an apoptotic index of (25.94±2.69)%, significantly larger than that in the same group at 0 hour ( P<0.01). The SCS group exhibited a large number of apoptotic cells at 24 hours, with an apoptotic index of (62.97±3.22)%, significantly larger than those at 0 hour in the same group and at 24 hours in the NMP group ( P<0.01). In comparison with the SCS group at 24 hours, the amputated limbs in the NMP group showed red color in the appearance, no symptoms of ischemic muscle contracture and good joint movement despite slight edema in the subcutaneous layer. At 24 hours, the weight gain rate of the amputated limbs was (15.82±0.89)% in the NMP group, significantly higher than (0.97±0.28)% in the SCS group ( P<0.01). Conclusion:Compared with SCS, NMP with the red blood cell-containing perfusion fluid prepared with the allogeneic blood for the amputated limbs of pigs can alleviate the ischemic injury of the muscle fibers and inhibit the apoptosis of the muscle cells by sustaining stable energy and oxygen supply and balancing ion homeostasis and pH of the perfusion fluid.

By selecting stable and detectable drug prototypes or metabolites in sewage samples, near real-time detection of disease conditions can be achieved. This study selected oseltamivir carboxylate, the primary metabolite of first-line antiviral oseltamivir, as a biomarker. Based on the concentration of oseltamivir carboxylate in wastewater, the consumption and usage rate of oseltamivir were calculated by reverse engineering. Quarterly sampling was conducted at 46 urban sewage treatment plants in representative 5 cities in the middle and lower reaches of the Yangtze River, from November 2022 to December 2023. The concentration range of oseltamivir acid in sewage samples is 1.270−1 279 ng/L, the daily mass load of oseltamivir per 1 000 inhabitants in the surveyed cities ranged from 9.560 to 544.7 mg/d, and the average utilization rate is 0.06‰−3.63‰. The research results indicate that in March 2023, Wuxi City experienced a spring influenza peak, while Bengbu, Tongling, Suzhou, and Changzhou City experienced a small summer influenza peak in May. In November and December 2023, Wuxi, Changzhou, and Bengbu City experienced a winter influenza peak, the results are consistent with the official statistics of the National Center for Disease Control and Prevention and the National Influenza Center, which reflect the influenza epidemic situation in southern cities. The integration of this methodology with clinical diagnostic rates could provide near real-time data support for future influenza prevention and control strategies.

Erector spinae plane block(ESPB)is a fascia plane block technique that involves injecting local anesthetics between the erector spinae muscle and the transverse processes of the spine.It blocks the posterior branches of the spinal nerves to provide perioperative analgesia for spinal surgeries.In recent years,ESPB has been increasingly widely used in spinal surgery analgesia due to its relatively simple operation,high safety and significant clinical benefits.However,its mechanism of action and the best application strategy still need to be further explored.This article systematically reviews the anatomical basis,mechanism of action,op-eration methods,drug selection,analgesic effect in various spinal surgeries,comparative advantages with other commonly used analgesic methods,and potential complications of ESPB,aiming to provide a reference for the clinical application of ESPB.

Remimazolam is a novel ultra-short-acting benzodiazepine characterized by rapid metabolism via hydrolysis by non-specific esterases.This mechanism enables fast onset and quick recovery,significantly shortening the duration of anesthesia and effectively reducing the risk of drug accumulation in the body.It ex-hibits high binding specificity for the γ-aminobutyric acid(GABA)receptor,leading directly to central nerv-ous system inhibition and producing a pronounced sedative effect.This profile offers a more precise and con-trollable approach to anesthesia in clinical practice.The safety and efficacy of remimazolam have been demon-strated across various clinical settings,including procedural sedation,induction and maintenance of general an-esthesia,and sedation in the intensive care unit(ICU).Its adverse effects are relatively infrequent and highly predictable,as substantiated by numerous clinical trials;however,the optimization of its dosing regimens re-quires further in-depth investigation.This review summarized the pharmacological properties of remimazolam and provides a detailed discussion on the impact of various factors on its pharmacodynamics.These factors in-clude basic patient characteristics(such as gender,age,obesity,hepatic and renal function,and circadian rhythms)and external influences(such as altitude and drug interactions).