OBJECTIVE: To summarize the gene therapy strategies for neurofibromatosis type 1 (NF1) and related research progress. METHODS: The recent literature on gene therapy for NF1 at home and abroad was reviewed. The structure and function of the NF1 gene and its mutations were analyzed, and the current status as well as future prospects of the transgenic therapy and gene editing strategies were summarized. RESULTS: NF1 is an autosomal dominantly inherited tumor predisposition syndrome caused by mutations in the NF1 tumor suppressor gene, which impair the function of the neurofibromin and lead to the disease. It has complex clinical manifestations and is not yet curable. Gene therapy strategies for NF1 are still in the research and development stage. Existing studies on the transgenic therapy for NF1 have mainly focused on the construction and expression of the GTPase-activating protein-related domain in cells that lack of functional neurofibromin, confirming the feasibility of the transgenic therapy for NF1. Future research may focus on split adeno-associated virus (AAV) gene delivery, oversized AAV gene delivery, and the development of new vectors for targeted delivery of full-length NF1 cDNA. In addition, the gene editing tools of the new generation have great potential to treat monogenic genetic diseases such as NF1, but need to be further validated in terms of efficiency and safety. CONCLUSION Gene therapy, including both the transgenic therapy and gene editing, is expected to become an important new therapeutic approach for NF1 patients.
Humans ; Neurofibromatosis 1/pathology* ; Neurofibromin 1/metabolism* ; GTPase-Activating Proteins ; Mutation ; Genetic Predisposition to Disease ; Genetic Therapy

In the field of dental aesthetics,digital aesthetic design plays a crucial role in helping dentists to predict treatment outcomes vis-ually,as well as in enhancing the consistency of knowledge and understanding of aesthetic goals between dentists and patients.It serves as the foundation for achieving ideal aesthetic effects.However,there is no clear standard for this digital process currently in China and abroad.Many dentists lack of systematic understanding of how to carry out digital aesthetic design for treatment.To establish standardized processes for dental aesthetic design and to improve the homogeneity of treatment outcomes,Chinese Society of Digital Dental Industry(CSD-DI)convened domestic experts in related field to compile this consensus.This article elaborates on the key aspects of digital aesthetic data collection,integration steps,and the digital aesthetic design process.It also formulates a decision tree for dental aesthetics at macro level and outlines corresponding workflows for various clinical scenarios,serving as a reference for clinicians.

Objective To observe the effects of a 1 470 nm semiconductor laser on vaporization cutting,coagulation,and thermal injury of ex vivo animal tissues,aiming to explore the feasibility of its application in the treatment of benign prostatic hyperplasia.Methods The experimental group and control group were treated with HANS-D1 and ML-DD01FI 1 470 nm semiconductor laser therapy equipment,respectively.Fresh ex vivo pig bladder tissue was exposed to lasers with the optical fiber placed at distances of 0.5 cm and 1 cm from the tissue for 5 s.The effects of layers at powers of 60,90,120,150,and 160 W on tissue injury were observed.Ex vivo dog prostate and pig kidney tissues were used for vaporization ablation and cutting to observe the effects of lasers at the same power levels on tissue vaporization and cutting thermal injury.Additionally,in coagulation mode,the effects of 30,40,and 50 W semiconductor lasers on tissue coagulation were observed after irradiating ex vivo pig kidney tissue for 5,10,and 15 seconds.Results When the optical fiber was placed 1 cm away from the tissue,the 1 470 nm semiconductor lasers did not cause accidental damage to adjacent normal bladder tissue.However,at a distance of 0.5 cm,the 120 W,150 W,or 160 W lasers caused slight damage to the bladder tissue.In addition,with the increase in output power,the vaporization ablation efficiency of 60-160 W lasers on dog prostate tissue gradually increased,showing a good linear correlation between vaporization volume and total energy consumption(P＜0.001).Histopathological HE staining results indicated that the coagulation layer thickness in the experimental group was 292.20-309.98 μm,and the vaporization layer depth was 1.49-4.52 mm.In the control group,the coagulation layer thickness was 289.91-303.53 μm,and the vaporization layer depth was 1.88-4.43 mm.There was no significant difference between the two groups(P＞0.05).Moreover,when performing vaporization cutting on ex vivo pig kidney tissue with a cross-sectional area of 1 cm2,the efficiency of vaporization cutting by the 60-160 W 1 470 nm semiconductor lasers increased with the increase in output power(P＜0.05).The coagulated layer thickness in the experimental group was 496.04-514.47 μm,while that in the control group was 489.39-518.53 μm.Additionally,in coagulation mode,when ex vivo pig kidney tissue was irradiated for 5,10,and 15 s with 30,40,and 50 W semiconductor lasers,the coagulation diameter,groove depth,and coagulation efficiency gradually increased with the increase in laser output power(P＜0.05).The coagulation layer thickness in the experimental group and control group was 399.10-449.98 μm and 392.97-447.65 μm,respectively,and the vaporization layer depth was 3.05-7.09 mm and 2.70-7.14 mm,respectively.There was no significant difference between the two groups(P＞0.05).Conclusion The 1 470 nm semiconductor laser shows good vaporization ablation,cutting,and coagulation effect on ex vivo tissues,with a good linear correlation between the effect and the output energy.

Objective To evaluate the effectiveness of a 1470 nm semiconductor laser therapeutic instrument(referred to as a curestar therapeutic instrument)for prostatectomy in Beagle dogs.Methods Twenty-eight adult male Beagle dogs were randomly divided into three groups:sham(n=3),experimental(n=15),and control(n=10).The experimental group was further divided into three subgroups:120 W/50 W,150 W/50 W,and 160 W/50 W for vaporization cutting/coagulation hemostasis.The control group was divided into two subgroups:120 W/50 W and 150 W/50 W with five in each subgroup.Experimental and control groups underwent canine prostatectomy through the entrance of the bladder neck under electrocision.The operational suitability and effectiveness of the product during surgery were assessed.After the operation,the general condition of the dogs was observed,and blood biochemical and hematological indicators were measured before,immediately after,and at 3,7,and 28 days after the operation.At 1 h and 4 weeks after surgery,B-ultrasound and electric resection were performed under anesthesia to observe the conditions of the urethra and prostate,and prostatic tissue was subjected to HE staining for pathological observations.The thickness of the coagulation layer at 1 h after the operation and repair of the urothelial epithelium at 4 weeks were analyzed.Results During the operation,experimental and control groups had good operability and showed good vaporization cutting and coagulation hemostasis performance.After the operation,no significant effects were observed on the general condition,and blood biochemical and hematological indicators of the dogs.Ultrasound showed that the urethral expansion was visible immediately after the operation,and the echo of the urethral epithelium was slightly enhanced.At 4 weeks,the prostate tissue had a slightly low echo with uniformly distributed small point-like echoes inside,and the capsule had a linearly high echo,consistent with the sham group.The weight of the vaporized prostate tissue in experimental and control groups was 0.91～1.33 g with a resection rate of 17.11％～20.27％.As the power of vaporization cutting increased,the laser emission time gradually decreased,while the vaporization cutting speed and efficiency both increased.However,no significant difference was found between experimental and control groups(P＞0.05).Under the electrocision microscope,a burn-like change was observed in the surgical wounds of the prostate urethra in experimental and control groups at 1 h after surgery,and the boundary between the wound and normal urothelium was visible.At 4 weeks,the urothelium of the prostate had been repaired and flattened,and the boundary with the surrounding normal urothelium was blurred.Similarly,pathological observations showed that experimental and control groups had significant damage to the prostate urethral orifice at 1 h after surgery with a small amount of carbonization and coagulative necrosis on the surface of the wound,a small amount of inflammatory cell infiltration,and a coagulation layer thickness of approximately 0.4 mm.At 4 weeks,the prostate urethral morphology of the sham group was normal,whereas experimental and control groups showed new epithelial growth covering the wound with a uniform thickness and no coagulative necrosis tissue attached to the wound.A mild inflammatory reaction was still present in the surrounding area,fibroblast proliferation was obvious,and stromal and epithelial cell proliferation was visible in the surrounding prostate,some of which showed squamous metaplasia.The prostate capsule was intact and the morphology of the surrounding nerves and blood vessels was normal.Conclusions The curestar therapy instrument is effective for prostatectomy in Beagle dogs with good vaporization cutting and coagulation hemostasis performance.No significant difference was found in postoperative physiological indicators compared with the sham group.

Objective:To evaluate the outcome of endoscopic submucosal dissection (ESD) of colorectal tumors, and to analyze the factors affecting the therapeutic efficacy of ESD.Methods:Clinical data of patients with colorectal tumors who were treated with ESD in Department of Gastroenterology in Beijing Hospital from November 2016 to December 2019 were reviewed. A total of 82 patients with pathologically confirmed colorectal adenoma or carcinoma of diameter ≥20 mm were included. The clinical features, ESD and pathological outcomes of the patients were analyzed.Results:All 82 lesions were single, with the mean diameter of 29.72±10.74 mm. Lesions were divided into the laterally spreading tumors (LST), mainly located in the ascending colon and ileocecal region (47.8%, 22 / 46) and the protruding colorectal tumors, mainly located in the left colon, 52.8% (19 / 36) of which were located in the sigmoid colon. The overall resection rate was 81.7%(67/82) and the curative resection rate was 72.0%(59/82). The incidences of bleeding and perforation were 2.4%(2/82) and 1.2%(1/82), respectively. The curative resection rates [91.4%(32/35), 63.6%(7/11) and 55.6%(20/36), P=0.003] and surgical operation rates [8.6%(3/35), 18.2%(2/11) and 36.1%(13/36), P=0.010] of LST-G, LST-NG and protruding colorectal tumors were significantly different. Multivariate regression analysis showed that protruding colorectal tumor ( OR=3.396, 95% CI: 1.014-11.374, P=0.047) and submucosal severe fibrosis (F2 type) ( OR=5.508, 95% CI: 2.216-13.692, P=0.001) were independent risk factors for non-curative ESD resection of colorectal tumors. Conclusion:ESD is effective and safe for colorectal tumors of diameter ≥ 20 mm. However, there are some differences in the rate of submucosal invasion and treatment outcome among different types of lesions. The risk factors for non-curative resection are protruding tumors and severe submucosal fibrosis.

This paper mainly studied the effect of Xiyanping injection on the bacterial endotoxin lipopolysaccharide (LPS)-induced fever in rabbits, preliminarily investigated the mechanisms, and provided pharmacological basis for the clinical application. The rabbit model of endotoxin-induced fever was established by using LPS as the inducer; The changes of rectal temperature were measured; The levels of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and phospholipaseA2 (PLA2) in the serum were measured; The levels of PGE2, cyclic adenosine monophosphate (cAMP), and arginine vasopressin (AVP) in cerebrospinal fluid as well as hypothalamus were detected. The animal welfare and experimental process are in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University in this study. The results showed that Xiyanping injection (12.5, 25, and 50 mg·kg^-1) could significantly reduce LPS-upregulated body temperature of rabbits, and the duration of action could reach 5.5-8.5 h. At the doses of 25 and 50 mg·kg^-1, the antipyretic effect of Xiyanping injection was comparable to that of analgin injection (50 mg·kg^-1). Furthermore, Xiyanping injection and analgin injection both reduced the levels of PGE2, IL-1β, TNF-α, and PLA2 in the serum of febrile rabbits to the varying degrees. In addition, Xiyanping injection also down-regulated the levels of PGE2, cAMP, and AVP in the hypothalamus, and PGE2 and cAMP in the cerebrospinal fluid. The level of AVP in the cerebrospinal fluid was up-regulated. This study indicated that Xiyanping injection could significantly improve the endotoxin-induced fever in rabbits, and mechanisms were closely related to the regulation of the levels of PGE2, TNF-α, IL-1β, PLA2, cAMP, and AVP in serum, hypothalamus, and cerebrospinal fluid.

Objective To investigate the characteristics of five hormone levels of hypertension in patients with essential hypertension,and explore the correlation between them and essential hypertension.Methods The clinical data of 1 731 patients with essential hypertension and 305 healthy people in General Hospital of Heilongjiang Province Land Reclamation Bureau from April 2018 to March 2019 were analyzed retrospectively.The levels of renin,angiotension Ⅱ (AT Ⅱ),aldosterone,adrenocorticotropic hormone (ACTH) and cortisol were measured by magnetic particle chemiluminescence,and the ratio of aldosterone to renin (ADRR) was calculated.Results The renin,AT Ⅱ,aldosterone,ACTH,cortisol and ADRR in patients with essential hypertension were significantly higher than those in healthy controls:(13.58 ± 9.78) ng/L vs.(9.20 ± 2.12) ng/L,(181.06 ± 89.82) ng/L vs.(133.49 ± 5.47) ng/L,(174.96 ± 103.14) ng/L vs.(136.04 ± 15.48) ng/L,(76.39 ± 61.43) ng/L vs.(26.98 ± 5.10) ng/L,(176.4 ± 88.8) μg/L vs.(145.1 ± 18.9) μg/L and 27.71 ± 18.37 vs.15.18 ± 1.77,and there were statistical differences (P＜0.01).The renin and AT Ⅱ in male patients with essential hypertension (904 cases) were significantly higher than those in female patients with essential hypertension (827 cases):(16.04 ± 10.67) ng/L vs.(10.34 ± 8.59) ng/L and (194.28 ± 96.22) ng/L vs.(166.37 ± 83.42) ng/L,the aldosterone was significantly lower than that in female patients with essential hypertension:(166.31 ± 101.91) ng/L vs.(184.68 ± 104.37) ng/L,and there were statistical differences (P＜0.01 or ＜0.05);there were no statistical difference in ACTH,cortisol and ADRR (P＞0.05).The renin and AT Ⅱ in patients aged 51 to 60 years (610 cases) and ＞60 years (572 cases) were significantly lower than those in patients aged ＜ 50 years (549 cases):(12.67 ± 10.76),(12.43 ± 8.29) ng/L vs.(16.05 ± 10.29) ng/L and (172.62 ± 81.63),(166.04 ± 79.09) ng/L vs.(208.94 ± 108.75) ng/L,and there were statistical differences (P＜0.05 or ＜0.01);there were no statistical difference in aldosterone,ACTH,cortisol and ADRR (P＞0.05).Multivariate linear regression analysis result showed that renin and AT Ⅱ were negatively correlated with systolic blood pressure and diastolic blood pressure (P＜0.01 or ＜0.05),and aldosterone,ACTH and cortisol were positively correlated with systolic blood pressure and diastolic blood pressure (P＜0.05 or ＜0.01).Conclusions Renin and AT Ⅱ are negatively correlated with systolic blood pressure and diastolic blood pressure;aldosterone,and ACTH and cortisol are positively correlated with systolic blood pressure and diastolic blood pressure.The five hormone levels of hypertension can reflect the function of renin-angiotension-aldosterone (RAAS) system and hypothalamus pituitary adrenocortical axis (HPA axis),which are the influencing factors of essential hypertension.

Objective:To investigate the impact of the destruction of dorsal motor nucleus of the vagus(DMV)on lower esophageal sphincter pressure in a rat model of acute esophagitis.Methods:A total of 40 male Sprague-Dawley(SD)rats were randomly divided into four groups: the control group, sham group, DMV destruction group, DMV destruction + vagal stimulation group.Two weeks after DMV destruction or sham operation, hydrochloric acid with pepsin was perfused into the esophagogastric junction of rats for 90 min, and lower esophageal sphincter pressure was measured before and after operation and 60 min after acid perfusion.Rats in the control group received assessment of lower esophageal sphincter pressure directly.Rats in the DMV destruction + vagus stimulation group were given electric current stimulation for 30 minutes before and after 15 min of esophageal acid perfusion.Rats were sacrificed after 60 min of the acid perfusion.The esophagus was prepared for hematoxylin and eosin(HE)staining, and the degree of inflammation and the expression of inflammatory cytokines were examined.Results:In the DMV destruction group, lower esophageal sphincter pressure decreased 2 weeks after DMV destruction compared with pre-destruction levels(25.9±8.8 cmH 2O vs.34.0±8.9 cmH 2O, P<0.05), and lower esophageal sphincter pressure decreased after 60 min of acid perfusion compared with pre-destruction levels(18.6±3.6 cmH 2O vs.25.9±8.8 cmH 2O, P<0.01). In the DMV destruction + vagus stimulation group, lower esophageal sphincter pressure increased after vagus nerve stimulation(22.3±2.9 cmH 2O vs.18.6±3.6 cmH 2O, P<0.05). There was no significant difference in lower esophageal sphincter pressure in the sham group before and after sham operation, while the pressure increased after acid perfusion(30.0± 9.5 cmH 2O vs.37.8±5.8 cmH 2O, P<0.05). The degree of inflammation in the lower esophagus was aggravated and the expression of tumor necrosis factor-α, interleukin(IL)-6, IL-1β and prostaglandin E2 in esophageal tissues increased in the DMV destruction group compared with the sham group( P<0.01). The inflammation degree and the expression of inflammatory factors in the lower esophagus improved after vagal nerve stimulation compared with pre-stimulation levels( P<0.01). Conclusions:DMV destruction decreases lower esophageal sphincter pressure and aggravates esophageal inflammation and injury in a rat model of acute esophagitis.Vagus nerve stimulation can strengthen the pressure of the lower esophageal sphincter and improve the inflammation of the lower esophageal segment.

Two new phenylpropanoid amide glycosides and ten analogues were isolated from the CH_2Cl_2 layer of 95% ethanol extract of the whole plants of Corydalis racemosa by using various chromatographic techniques, including silica gel, Sephadex LH-20, ODS column chromatographies, and semi-preparative HPLC. Their structures were identified on the basis of physicochemical properties, MS, NMR, and IR spectroscopic data as N-cis-sinapoyltyramine-4'-O-β-glucoside(1), N-cis-sinapoyl-3-methoxytyramine-4'-O-β-glucoside(2), N-cis-sinapoyltyramine(3), N-cis-feruloyltyramine(4), N-trans-cinnamoyltyramine(5), N-trans-feruloylphenethylamine(6), N-trans-p-methoxycinnamoyl-3-hydoxyoctopamine(7), N-cis-feruloyl-3-methoxytyramine(8), N-trans-feruloyltyramine(9), N-trans-feruloyl-3-methoxytyramine(10), N-trans-sinapoyltyramine(11), and N-trans-p-coumaroyltyramine(12). Compounds 1 and 2 are new compounds. Compounds 3-7 are obtained from the plants of Papaveraceae for the first time, and compounds 8-12 are firstly isolated from C. racemosa.
Amides ; Chromatography, High Pressure Liquid ; Corydalis ; Glucosides ; Glycosides

This study is to investigate the chemical constituents from the whole plant Corydalis edulis. The chemical constituents were separated and purified by macroporous resin D101, silica gel, Sephadex LH-20, ODS, and semi-preparative HPLC. Their structures were determined by physicochemical properties and spectroscopic data. Four compounds were isolated from the dichloromethane and water extracts of the whole plant C. edulis, and identified as 6'-β-D-xylosylicariside B2(1),(3S,5R,6S,7E)-5,6-epoxy-3-hydroxy-7-megastigmen-9-one(2), loliolide(3), and 5,5'-dimethoxybiphenyl-2,2'-diol(4), respectively. Compound 1 is a new compound, of which the absolute configuration was established by electronic circular dichroism(ECD) calculations. Compound 4 is obtained from the plants of Papaveraceae family for the first time. Compounds 2 and 3 are firstly isolated from the Corydalis genus.
Chromatography, High Pressure Liquid ; Corydalis/chemistry* ; Glycosides/isolation & purification* ; Molecular Structure ; Phytochemicals/isolation & purification* ; Sesquiterpenes/isolation & purification*