1.Use of ferrets in nonclinical studies of anti-infective drugs
Xuewu LIU ; Zining TANG ; Dongdong PENG ; Yanhua DU ; Dejian JIANG
Acta Laboratorium Animalis Scientia Sinica 2024;32(6):799-818
Ferrets offer an advantage in nonclinical studies of anti-infective drugs because of their ability to be infected with and spread pathogenic microorganisms,especially viral strains,without the need for host adaptation.Additionally,the clinical symptoms exhibited by infected ferrets are very similar to those of humans.Although ferrets play a very important role in the research and development of antiviral drugs,the scope of their application remains limited.This may be related to the lack of corresponding national standards for laboratory animal feeding and application of ferrets as well as the lack of specific diagnostic and detection reagents.This paper summarizes the characteristics of ferrets as infectious disease models with a summary and analysis of the application direction of ferrets in anti-infective drug research.Our aim is to promote further standardization of the use of ferrets.
2.Clinical phenotype and genotype analysis of a Chinese family with congenital aniridia caused by a novel frameshift and nonsense variant in PAX6
Dongdong WANG ; Jiao DU ; Zixu HUANG ; Handong DAN ; Zuopeng LIN ; Zongming SONG
Chinese Journal of Experimental Ophthalmology 2024;42(10):927-931
Objective:To analyze the clinical manifestations and explore the etiology in a family with congenital aniridia and to analyze the influence of candidate variants on the protein structure.Methods:A pedigree investigation was performed.A Han Chinese family with congenital aniridia of two generations consisting of three members from Henan Province, including one patient diagnosed with congenital aniridia, was identified and studied following their admission to Henan Eye Hospital in June 2023.A thorough medical history was obtained for the patient and their family members.Comprehensive ophthalmologic examinations were conducted, including visual acuity, intraocular pressure, anterior segment photography, color fundus photography, ultrasound biomicroscopy, and optical coherence tomography, etc.Peripheral blood samples were obtained from the family members and whole exome sequencing (WES) was performed on the patient and validated by Sanger sequencing for other members.The pathogenicity and protein structure of newly identified variant sites were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2023[06]).Written informed consent was obtained from each subject.Results:The proband is a 23-year-old male presenting with poor binocular vision, aniridia, corneal degeneration, mild lens opacity, shallow anterior chamber, elevated intraocular pressure, peripheral retinal degeneration, and macular dysplasia.The clinical phenotype of the proband's parents did not show any significant abnormality.WES identified a heterozygous frameshift and nonsense varint c. 734_735del (p.Arg245Asnfs*20) in exon 10 of the PAX6 gene, which consisited of two bases deletion at positions 734 to 735, resulting in the mutation of its arginine at position 245 to asparagine and the early appearance of a termination codon at the next 19 amino acids.The variant had not been identified in the HGMD, Clinvar, 1 000 Genomes, and gnomAD databases.Neither of the proband's parents carried the variant, consistent with the pattern of family co-segregation.Substructural analysis using the SMART tool indicated that the variant is situated within the HOX domain.Amino acid conservation analysis demonstrated that the arginine residue at position 245 in the PAX6 gene is highly conserved across multiple species, including human, house mouse, domestic dog, African clawed frog, and macaque.The variant was classified as pathogenic (PVS1+ PS2+ PM2+ PP3) based on the ACMG standards and guidelines for the interpretation of sequence variants.Protein structure analysis revealed the absence of both the homologous domain and the proline-serine-threonine-rich domain in the PAX6 protein. Conclusions:A novel pathogenic variant, c.734_735del (p.Arg245Asnfs*20), in the PAX6 gene has been identified in a family affected by congenital aniridia.This variant results in the deletion of both the PAX6 protein homology domain and the proline-serine-threonine-rich domain.
3.A multi-center observation of the therapeutic efficacy of Bencycloquidium bromide in the treatment of seasonal allergic rhinitis with predominant symptoms of rhinorrhea.
Weini HU ; Tianhong ZHANG ; Yinghong ZHANG ; Chao MENG ; Lifeng XIE ; Yu SONG ; Chen DU ; Chiyu XU ; Yali DU ; Qiang ZUO ; Fengyang AN ; Yuhui WANG ; Cuida MENG ; Lei ZHANG ; Dongdong ZHU ; Li ZHU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(7):550-555
Objective:To observe the efficacy and safety of the M receptor antagonist Bencycloquidium bromide nasal spray in treatment of seasonal allergic rhinitis with runny nose as the main symptom. Methods:From August 2021 to September 2021, 134 patients with seasonal allergic rhinitis were enrolled in the otolaryngology Outpatient Department of Peking University Third Hospital, First Affiliated Hospital of Harbin Medical University and China-Japanese Friendship Hospital of Jilin University, including 71 males and 63 females, with a median age of 38 years. TNSS score and visual analogue scale(VAS) of total nasal symptoms were observed during 2 weeks of treatment with Bencycloquidium bromide nasal spray. Results:TNSS score decreased from (8.89±3.31) on day 0 to (3.71±2.51) on day 14(P<0.001), VAS score of nasal symptoms decreased from (24.86±7.40) on day 0 to (6.84±5.94) on day 14(P<0.001), VAS score of rhinorrhoea decreased from (6.88±2.06) on day 0 to (1.91±1.81) on day 14(P<0.001). Rhinoconjunctivitis quality of life questionnaire(RQLQ) score decreased from (94.63±33.35) on day 0 to (44.95±32.28) on day 14(P<0.001). The incidence of adverse reaction was low and no serious adverse events occurred during the whole experiment. Conclusion:Bencycloquidium bromide nasal spray has significant efficacy and good safety in the treatment of seasonal allergic rhinitis.
Male
;
Female
;
Humans
;
Adult
;
Rhinitis, Allergic, Seasonal/drug therapy*
;
Nasal Sprays
;
Quality of Life
;
Administration, Intranasal
;
Rhinorrhea
;
Double-Blind Method
;
Treatment Outcome
;
Rhinitis, Allergic/drug therapy*
4.CRP is an important factor affecting the timing of surgical drainage of ureteral calculi with upper urinary tract infection
Fangzhou LI ; Qiang LIU ; Dongdong XIAO ; Zhebin DU ; Hanqing XUAN ; Qi CHEN ; Lianhua ZHANG
Journal of Modern Urology 2023;28(5):417-420
【Objective】 To explore the timing of surgical drainage for ureteral calculi with upper urinary tract infection. 【Methods】 Clinical data of 117 cases of ureteral calculi with upper urinary tract infection treated in our hospital during Jan.2018 and Jan.2020 were retrospectively analyzed. According to different treatment methods, the patients were divided into surgical drainage group and non-surgical drainage group. The patients’ age, gender, side of calculi, peak body temperature, time of onset, white blood cell (WBC) count, C-reactive protein (CRP) and other clinical indicators were compared between the two groups. The cutoff value of surgical drainage was determined with receiver operator characteristic (ROC) curve. 【Results】 The patients’ age, peak body temperature, WBC count and CRP level were the influencing factors of surgical drainage (P<0.05). Regression analysis showed that CRP (P<0.001), age (P=0.003) and WBC count (P=0.014) were independent risk factors for surgical drainage. The area under the ROC curve (AUC) of CRP, age, and WBC count were 0.923, 0.601, and 0.796, respectively. The cutoff value of CRP was 29.87 mg/L (sensitivity 79.4%, specificity 90.0%). Logistic regression model showed CRP was a significant clinical predictor. 【Conclusion】 Ureteral calculi with upper urinary tract infection need to be diagnosed and treated in time. Positive anti-infection should be performed during emergency treatment, and surgical drainage could be selected according to the value of CRP.
5.Integrative treatment for primary liver cancer with tumor thrombosis in hepatic vein or inferior vena cava: a review
Sihao DU ; Zhenshun WANG ; Dongdong LIN
Chinese Journal of Hepatobiliary Surgery 2023;29(1):62-66
Primary liver cancer is a common malignant tumor. Early liver cancer is suitable for surgical resection, local ablation, liver transplantation and other radical treatment, and the prognosis is better. Patients with advanced liver cancer often have tumor thrombosis in hepatic vein and inferior vena cava. With high rates of recurrence and metastasis, the prognosis is poor. Chinese guidelines recommend multidisciplinary treatment to patients with hepatic vein thrombosis and inferior vena cava thrombosis including local treatment, systematic anti-tumor drug treatment, surgical resection and other treatment. This article reviewed the progress in diagnosis and treatment of primary liver cancer with tumor thrombosis in hepatic vein and inferior vena cava in the past decade.
6.A comparative clinical study of non-motor symptoms in early Parkinson′s disease patients with body-first subtype and brain-first subtype
Dongdong WU ; Jing HE ; Kai LI ; Xinxin MA ; Huijing LIU ; Ying JIN ; Wei DU ; Yunfei LONG ; Wen SU ; Shuhua LI ; Haibo CHEN
Chinese Journal of Neurology 2023;56(10):1103-1111
Objective:To investigate the incidence of various non-motor symptoms (NMS) in early stage of Parkinson′s disease (PD) patients and the differences between the body-first and brain-first subtypes.Methods:A total of 121 patients with PD (Hoehn-Yahr stage 1-2) were recruited from PD Clinic, Department of Neurology, Beijing Hospital from January 2012 to January 2015. The general information and clinical features of the patients were collected. The minimal diagnostic criteria of parasomnias described in the International Classification of Sleep Disorders-Revised were used to diagnose rapid eye movement sleep behavior disorder (RBD).According to the sequence of RBD and motor symptoms, the patients were divided into 2 groups: body-first subtype and brain-first subtype. NMS was evaluated by the Non-Motor Symptom Questionnaire (NMSQuest). The clinical features and the incidence of various NMS were compared between the 2 groups. The Unified Parkinson′s Disease Rating Scale (UPDRS) was used to evaluate the severity of the disease, and its third part (UPDRS-Ⅲ) was used to evaluate the motor function of the patients. Hamilton Rating Scale for Depression (HAMD) and Hamilton Rating Scale for Anxiety (HAMA) were used to evaluate the depression and anxiety status of the patients. The sleep status of patients was assessed by Parkinson′s Disease Sleep Scale (PDSS). The quality of life of the patients was assessed by 39-item Parkinson′s Disease Questionnaire (PDQ-39).Results:Of all the patients, 49.59% (60/121) had the body-first subtype and 50.41% (61/121) had the brain-first subtype of PD. There was no significant difference in UPDRS-Ⅲ score between the 2 groups. The average number of NMS in all PD patients was 10.97±4.88. Body-first subtype patients had higher NMS incidence than brain-first subtype in difficulty in swallowing [46.7% (28/60) vs 23.0% (14/61), χ 2=7.507, P=0.006], nausea and vomiting [16.7% (10/60) vs 3.3% (2/61), χ 2=6.069, P=0.014], constipation [85.0% (51/60) vs 55.7% (34/61), χ 2=12.393, P<0.001], fecal incontinence [8.3% (5/60) vs 0 (0/61), χ 2=5.302, P=0.021], difficulty in remembering recent events [58.3% (35/60) vs 32.8% (20/61), χ 2=7.962, P=0.005], loss of interest [43.3% (26/60) vs 24.6% (15/61), χ 2=4.743, P=0.029], inattention [45.0% (27/60) vs 19.7% (12/61), χ 2=8.884, P=0.003], depression [55.0% (33/60) vs 34.4% (21/61), χ 2=5.181, P=0.023], intense vivid dreams [73.3% (44/60) vs 39.3% (24/61), χ 2=14.196, P<0.001] and restless legs [53.3% (32/60) vs 27.9% (17/61), χ 2=8.140, P=0.004]. The differences were significant. Body-first subtype and NMSQuest ( r=-0.489, P<0.001), UPDRS ( r=-0.189, P=0.038), HAMD ( r=-0.231, P=0.011), HAMA ( r=-0.298, P=0.001) and PDQ-39 scores ( r=-0.276, P=0.002) were negatively correlated. Body-first subtype and PDSS score was positively correlated. NMSQuest (Δ R2=0.265, P<0.001) was the main determinant of PDQ-39 score. Conclusions:PD patients are accompanied by various NMS, which is a major factor affecting the quality of life. Compared with brain-first subtype, body-first subtype might have more NMS burden and higher incidence rate in most NMS in early PD patients.
7.The effect of vitrectomy in the treatment of different types of chorioretinal coloboma with retinal detachment
Jiao DU ; Xiaoli LI ; Zun ZHAO ; Dongdong WANG ; Handong DAN ; Pingling SHI ; Zixu HUANG ; Suhan WANG ; Qiongqiong YUAN ; Zongming SONG
Chinese Journal of Ocular Fundus Diseases 2023;39(12):969-973
Objective:To observe the efficacy of pars plana vitrectomy (PPV) in the treatment of different types of chorioretinal coloboma with retinal detachment (RD).Methods:A single-center, retrospective clinical study. From April 2021 to March 2023, 24 eyes of 23 patients who were diagnosed as chorioretinal coloboma with RD in Henan Provincial Eye Hospital were included in this study. There were 11 males with 12 eyes and 12 females with 12 eyes. The mean age was (33.3±13.7) years old. Best corrected visual acuity (BCVA), spectral domain optical coherence tomography were performed. The BCVA examination was performed using a international standard logarithmic visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. According to the types of chorioretinal coloboma, the affected eyes were divided into the coloboma involved the optic disc group and the coloboma not involved the optic disc group, with 15 eyes and 9 eyes. According to whether the RD containing the coloboma area, the affected eyes were divided into RD containing the coloboma area group and the RD not containing the coloboma area group, with 15 eyes and 9 eyes. All eyes underwent standard pars plana three-channel 25G PPV, retinal laser photocoagulation combined with silicone oil tamponade. The follow-up time after surgery was (19.5±16.3) months. The last follow-up was the time point for efficacy determination. The retinal reattachment, BCVA recovery and postoperative complications were observed. Paired t-test or t test was performed for comparison of quantitative data. Fisher's exact test was performed for comparison of qualitative data. Results:At the last follow-up, retinal reattachment was achieved in 20 eyes (83.3%, 20/24). The logMAR BCVA of the coloboma involved the optic disc group before and after surgery were 1.85±0.62 and 1.71±0.71, the difference was no significant ( t=0.845 , P=0.412). The logMAR BCVA of the coloboma not involved the optic disc group before and after surgery were 1.75±0.45 and 0.84±0.26, the difference was statistically significant ( t=6.153 , P<0.001). The improvement of BCVA in the coloboma not involved the optic disc group was significantly higher than that in the coloboma involved the optic disc group after surgery, with statistically significant differences ( t=3.024 , P=0.006). There was no significant difference in the retinal reattachment rate between the two groups ( P=0.615). There was no significant difference in the retinal reattachment rate between the RD containing the coloboma area group and the RD not containing the coloboma area group ( P=0.259). Postoperative complications included elevated intraocular pressure in five eyes, cataract progression in ten eyes, recurrent RD in two eyes, bullous keratopathy in one eye and band-shaped keratopathy in one eye. Conclusion:PPV combined with silicone oil tamponade is safe and effective in the treatment of chorioretinal coloboma with RD, the improvement of visual acuity in the coloboma not involved the optic disc group is better than that in the coloboma involved the optic disc group after surgery.
8.Use of anticoagulant mechanical methods after laparoscopic sleeve gastrectomy for obese patients
Kai LI ; Chen LIU ; Nengwei ZHANG ; Jirun PENG ; Bin ZHU ; Dexiao DU ; Dongbo LIAN ; Dongdong ZHANG ; Ke GONG
Chinese Journal of General Surgery 2022;37(1):39-43
Objective:To investigate anticoagulant effects of mechanical methods in obese patients undergoing laparoscopic sleeve gastrectomy (LSG).Methods:In this prospective study, 54 obese patients receiving LSG were enrolled . All patients were given post-op mechanical methods for thrombogenic interventions. BMI and the operation-related factors were recorded. Venous blood specimens were taken from each patient before surgery, at the end of pneumoperitoneum (i.e., 0 h after surgery), at 24 hours after surgery for prothrombin time (PT) and activated partial thromboplastin time (APTT), fibrinogen (FIB) and D-dimer (D-D).Results:All 54 obese patients successfully underwent LSG. No severe complications were observed. Before operation, the mean BMI was (43.49±8.29) kg/m 2. DVT-2600 device was applied in all patients for 3 consecutive days after surgery. The PT values increased at 0 h, 24 h after surgery [(12.4±1.2) s, (12.4±0.8) s vs. (11.2±0.8) s, P=0, 0]. The APTT values at 0 h, 24 h after surgery decreased [(29.7±3.6) s, (29.0±3.1) s vs.(31.2±3.3) s, P=0.020, 0.001]. However, the D-D values increased at 0 h,24 h after operation [(213±143) ng/ml ,(445±237) ng/ml vs. (85±108) ng/ml, P=0, 0]. All patients were followed up for 1 month, and no thrombosis -related complications were observed. Conclusion:Mechanical methods for obese patients after LSG can help decrease the risk of deep venous thrombosis.
9.Clinical characteristics of subjective cognitive decline in patients with Parkinson′s disease and its relationship with affective symptoms: a preliminary study
Dongdong WU ; Wei DU ; Yunfei LONG ; Jing HE ; Huijing LIU ; Kai LI ; Xinxin MA ; Ying JIN ; Haibo CHEN
Chinese Journal of Neurology 2022;55(3):191-195
Objective:To investigate the characteristics and clinical related factors of Parkinson′s disease (PD) patients with subjective cognitive decline (SCD).Methods:Ninety-nine PD patients with normal cognitive function enrolled in Beijing Hospital from January to December 2018 were collected for the study. Patients with PD were divided into groups with ( n=57) and without ( n=42) SCD using the first question in Part 1 of the Unified Parkinson′s Disease Rating Scale (UPDRS). All patients were assessed by Montreal Cognitive Assessment (MoCA), modified Hoehn-Yahr grading, UPDRS, Hamilton Rating Scale for Depression (HAMD), Hamilton Rating Scale for Anxiety (HAMA), Parkinson′s Disease Sleep Scale, Ability of Daily Living Scale and 39-item Parkinson′s Disease Questionnaire (PDQ-39). Levodopa equivalent dose conversion was performed for patients taking anti-PD drugs. Patients′ self-reported years of formal education were collected. Results:The proportion of PD with SCD in this group was 57.58% (57/99). There were statistically significant differences in MoCA [28.00 (27.00, 29.00) vs 28.00 (27.00, 29.00) ,Z=-2.28, P=0.023], HAMD [6.00 (5.00, 8.50) vs 5.00 (2.00, 8.00), Z=-2.23, P=0.026], HAMA [7.00 (6.00, 11.00) vs 6.00 (3.00, 8.25) , Z=-2.70, P=0.007], PDQ-39-emotional health [2.00 (0, 5.00) vs 1.00 (0, 3.00), Z=-2.03, P=0.042] and PDQ-39-cognitive scores [4.00 (2.00, 5.00) vs 2.00 (0, 4.00), Z=-3.42, P=0.001] between PD with and without SCD groups. SCD was correlated with MoCA ( r=-0.23, P=0.022), HAMD ( r=0.23, P=0.025) and HAMA ( r=0.27, P=0.006) scores to varying degrees. When controlling for HAMD and HAMA scores, the correlation between SCD and MoCA scores ( r′=-0.18, P=0.084) was no longer existed. Conclusions:SCD is common in PD patients with normal cognitive function and is associated with poorer cognitive performance and more severe symptoms of depression and anxiety. In this group of patients, the relationship between SCD and affective symptoms may be greater than that of objective overall cognitive function, which is worthy of further studies.
10.Status quo and influencing factors of early social function in young and middle-aged patients with coronary heart disease after percutaneous coronary intervention
Huan ZHU ; Dan DU ; Dong JIA ; Xin WANG ; Wenhe GAO ; Lei WANG ; Shubao DONG ; Dongdong HUANG
Chinese Journal of Modern Nursing 2022;28(31):4366-4370
Objective:To explore the status of early social function in young and middle-aged patients after percutaneous coronary intervention (PCI) and analyze its influencing factors, so as to provide a basis for formulating relevant intervention measures.Methods:From July to December 2021, the convenient sampling method was used to select 110 young and middle-aged patients with coronary heart disease after PCI in the First Affiliated Hospital of Harbin Medical University as the research objects. The general information questionnaire, Social Disability Screening Schedule (SDSS) , Social Support Rate Scale (SSRS) and General Self-Efficacy Scale (GSES) were used to investigate the patients. Univariate analysis and multiple linear regression analysis were used to explore the influencing factors of early social function in young and middle-aged patients with coronary heart disease after PCI. A total of 110 questionnaires were distributed and 106 valid questionnaires were recovered, with an effective recovery rate of 96.36% (106/110) .Results:The scores of SDSS, SSRS and GSES of 106 young and middle-aged patients after PCI were (3.89±1.63) , (38.80±7.02) and (21.08±6.39) , respectively. The results of univariate analysis showed that there were statistically significant differences in SDSS scores among patients with different gender, family per capita monthly income, education level and number of stents ( P<0.01) . The results of multiple linear regression analysis showed that gender, family per capita monthly income, education level, number of stents, general self-efficacy and social support were the influencing factors of early social function in young and middle-aged patients with coronary heart disease after PCI ( P<0.05) . Conclusions:The status of early social function in young and middle-aged patients with coronary heart disease after PCI is not ideal. Medical staff should give more intervention and guidance to patients after PCI who are female, have a lower education level, have a lower per capita monthly family income and have a large number of stents, consider the influence of self-efficacy and social support on the social function of patients and formulate corresponding intervention measures according to the influencing factors, so as to improve the level of social function of patients.

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