ObjectiveBased on literature data mining， this study explores the modeling elements of diarrhea-predominant irritable bowel syndrome （IBS-D） animal models in China and abroad， providing references and suggestions for improving modeling methods and evaluation indicators. MethodsRelevant literature on IBS-D animal experiments from 2014 to 2024 was retrieved through computer searches in databases such as China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， Chinese Medical Journals Full-text Database， and PubMed. Information on experimental animal species， gender， body weight， modeling methods， modeling periods， intervention controls， modeling standards， and detection indicators was organized. Microsoft Excel 2021 software was used to establish a database and perform statistical analysis to examine the characteristics of IBS-D animal models. ResultsA total of 398 articles that met the inclusion criteria were reviewed. The IBS-D animal models were predominantly established using SD rats， Wistar rats， and C57BL/6 mice. Male animals were more commonly used， with rats typically aged 6-8 weeks and mice aged 4-6 weeks. In terms of interventions， piverium bromide was the main Western medicine， Tongxieyaofang was the primary Chinese medicine， and electroacupuncture was the primary acupuncture method. Among the modeling methods， the multi-factor combined composite modeling approach was the most common. Modeling periods were mainly concentrated between 1-14 days and 15-30 days. The success criteria for modeling were mainly evaluated based on the animal's general condition， fecal appearance， visceral sensitivity， gastrointestinal motility， behavior， and pathology. Detection indicators included apparent indexes， pathological markers， biochemical indicators， oxidative stress， brain-gut peptides， neurotransmitters， inflammatory factors， immune function， intestinal permeability， autophagy， apoptosis， proteins related to relevant signaling pathways， intestinal microbiota and its metabolites， etc. ConclusionThere are various methods for establishing IBS-D animal models， but no unified and universally accepted method has been established. The operation of the same modeling methods and the evaluation standards of the models vary across studies. Based on the results of data mining， the authors suggest that the multi-factor combined composite modeling approach most closely reflects the pathophysiological processes of IBS-D， better simulating the complex clinical symptoms of IBS-D patients， such as abdominal pain and diarrhea， and has a high degree of clinical relevance. This method is relatively recommended. While animal models in general align with Western medicine standards， models incorporating traditional Chinese medicine （TCM） syndromes are relatively few. Therefore， one of the future directions for research is to establish IBS-D animal models that meet the combined clinical disease and syndrome requirements of both Western and Chinese medicine.

The clinical antiprotozoal drug nitazoxanide has been demonstrated to improve the experimental diabetes mellitus, lipid metabolism disorders, atherosclerosis and inhibit inflammation. Since the pathogenesis of heart failure with preserved ejection (HFpEF) is multifactorial and closely associated with the aforementioned diseases, we aim to study the effect of nitazoxanide on high-fat diet (HFD) plus L-NAME (N ω-nitro-l-arginine methyl ester)-induced HFpEF and metabolic syndrome in mice. We found that oral nitazoxanide improved cardiac hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, increased blood pressure, impaired exercise tolerance, impaired glucose handling, serum lipid disorders, hepatic steatosis, increased weight of white adipose tissues and kidney fibrosis in HFD + L-NAME-treated mice. In the established HFD + L-NAME-induced HFpEF and metabolic syndrome mouse model, therapeutic treatment with nitazoxanide rescued HFD + L-NAME-induced pathological phenotypes as mentioned above. The in vitro experiments revealed that tizoxanide, the active metabolite of nitazoxanide, increased the basal mitochondria metabolism of cardiomyocytes, inhibited cardiomyocyte hypertrophy and collagen secretion from cardiac fibroblasts, and relaxed phenylephrine- and U46619-induced constriction of rat mesenteric arteries, indicating that the direct effect of tizoxanide might partly contribute to the protective effect of nitazoxanide against HFpEF in vivo. The present study suggests that nitazoxanide might be a potential drug for HFpEF and metabolic syndrome therapy.

Cocaine,as a widely abused and highly addictive drug,has a serious impact on the physical and mental health of individuals and carries a certain degree of social harm and economic burden.Acupuncture can assist in the treatment of cocaine addiction with fewer side effects.However,a well-defined mode of stimulation is an important factor in elucidating the various mechanisms by which acupuncture treats disease.This paper summarizes the problems in the mechanism of cocaine addiction,such as different parameters of stimulation,unstable depth of acupuncture,different acupoint selection,and different lengths of acupuncture time.To standardize the intervention measures of acupuncture experiments,it is suggested that in future research,the stimulation method should explore the best parameters,the selection of acupoints should be based on clinical practice,the timing of acupuncture should be objective,and the treatment course should consider the effects of acupuncture.

Objective: This study used cardiac magnetic resonance imaging (MRI) to compare the characteristics of left ventricular remodeling in patients with primary aldosteronism (PA) with those of patients with essential hypertension (EH) and healthy controls (HCs). Materials and Methods: This prospective study enrolled 35 patients with PA, in addition to 35 age- and sex-matched patients with EH, and 35 age- and sex-matched HCs, all of whom underwent comprehensive clinical and cardiac MRI examinations. The analysis of variance was used to detect the differences in the characteristics of left ventricular remodeling among the three groups. Univariable and multivariable linear regression analyses were used to determine the relationships between left ventricular remodeling and the physiological variables. Results: The left ventricular end-diastolic volume index (EDVi) (mean ± standard deviation [SD]: 85.1 ± 13.0 mL/m2 for PA, 75.9 ± 14.3 mL/m2 for EH, and 77.3 ± 12.8 mL/m2 for HC; p = 0.010), left ventricular end-systolic volume index (ESVi) (mean ± SD: 35.2 ± 9.8 mL/m2 for PA, 30.7 ± 8.1 mL/m2 for EH, and 29.5 ± 7.0 mL/m2 for HC; p = 0.013), left ventricular mass index (mean ± SD: 65.8 ± 16.5 g/m2 for PA, 56.9 ± 12.1 g/m2 for EH, and 44.1 ± 8.9 g/m2 for HC; p < 0.001), and native T1 (mean ± SD: 1224 ± 39 ms for PA, 1201 ± 47 ms for EH, and 1200 ± 44 ms for HC; p = 0.041) values were higher in the PA group compared to the EH and HC groups. Multivariable linear regression demonstrated that log (plasma aldosteroneto-renin ratio) was independently correlated with EDVi and ESVi. Plasma aldosterone was independently correlated with native T1. Conclusion Patients with PA showed a greater degree of ventricular hypertrophy and enlargement, as well as myocardial fibrosis, compared to those with EH. Cardiac MRI T1 mapping can detect left ventricular myocardial fibrosis in patients with PA.

Objective: This study used cardiac magnetic resonance imaging (MRI) to compare the characteristics of left ventricular remodeling in patients with primary aldosteronism (PA) with those of patients with essential hypertension (EH) and healthy controls (HCs). Materials and Methods: This prospective study enrolled 35 patients with PA, in addition to 35 age- and sex-matched patients with EH, and 35 age- and sex-matched HCs, all of whom underwent comprehensive clinical and cardiac MRI examinations. The analysis of variance was used to detect the differences in the characteristics of left ventricular remodeling among the three groups. Univariable and multivariable linear regression analyses were used to determine the relationships between left ventricular remodeling and the physiological variables. Results: The left ventricular end-diastolic volume index (EDVi) (mean ± standard deviation [SD]: 85.1 ± 13.0 mL/m2 for PA, 75.9 ± 14.3 mL/m2 for EH, and 77.3 ± 12.8 mL/m2 for HC; p = 0.010), left ventricular end-systolic volume index (ESVi) (mean ± SD: 35.2 ± 9.8 mL/m2 for PA, 30.7 ± 8.1 mL/m2 for EH, and 29.5 ± 7.0 mL/m2 for HC; p = 0.013), left ventricular mass index (mean ± SD: 65.8 ± 16.5 g/m2 for PA, 56.9 ± 12.1 g/m2 for EH, and 44.1 ± 8.9 g/m2 for HC; p < 0.001), and native T1 (mean ± SD: 1224 ± 39 ms for PA, 1201 ± 47 ms for EH, and 1200 ± 44 ms for HC; p = 0.041) values were higher in the PA group compared to the EH and HC groups. Multivariable linear regression demonstrated that log (plasma aldosteroneto-renin ratio) was independently correlated with EDVi and ESVi. Plasma aldosterone was independently correlated with native T1. Conclusion Patients with PA showed a greater degree of ventricular hypertrophy and enlargement, as well as myocardial fibrosis, compared to those with EH. Cardiac MRI T1 mapping can detect left ventricular myocardial fibrosis in patients with PA.

Tooth avulsion is one of the most serious case of all traumatic injuries, frequently found in the immature permanent teeth. The common treatment for avulsed permanent tooth is replantation and splint fixation. However it usually results in root inflammation, root absorption and ankylosis, eventually lead to extraction. The present report describes a 8-year-old boy with two immature mandibular central incisors avulsed three hours after the accident. Replantation was performed, and the teeth were splinted. Radiographic and clinical examinations were performed during 15 months follow-up. At present, the avulsed teeth have a favorable prognosis, and remained in a stable functional position and did not reveal root inflammation, root absorption and ankylosis.

Objective: To investigate the association between hyponatremia and hemodynamic and prognosis in patients with intermediate-risk acute pulmonary embolism. Methods: We retrospectively recruited 110 intermediate-risk acute pulmonary embolism patients (right ventricular dysfunction was confirmed by echocardiography and CT scan with or without the elevated levels of cardiac injury biomarkers) in the first and the second affiliated hospital of Harbin medical university from January 1,2011 to December 31, 2014. The patients were aged (58.4±14.9) years old.There were 49 males and 61 females.Patients were divided into 2 groups as non-hyponatremia group (plasma sodium>135 mmol/L, 93 cases) and hyponatremia group (plasma sodium≤135 mmol/L, 17 cases). Baseline clinical and hemodynamic parameters were obtained from these patients. All enrolled patients were followed up after discharge. Results: Heart rate ((106.7±21.9) beats per minute vs. (93.4±19.4) beats per minute, P=0.043),N-terminal pro B type natriuretic peptide (NT-proBNP, (5 561±1 593) ng/L vs. (1 738±589) ng/L, P=0.005), mean pulmonary arterial pressure((42.6±12.6)mmHg(1 mmHg=0.133 kPa) vs. (33.9±13.3)mmHg, P=0.046), mean right atria pressure ((20.6±8.1)mmHg vs. (10.2±5.4)mmHg, P=0.014), systolic right atria pressure ((27.3±9.0)mmHg vs. (15.6±6.1)mmHg,P=0.013) and diastolic right atria pressure(6.5(4.3,15.5)mmHg vs. 5.0(2.0,8.0)mmHg,P=0.016) were significantly higher in hyponatremia group than in non-hyponatremia group,and systolic blood pressure was significantly lower in hyponatremia group than in non-hyponatremia group ((113.5±21.9)mmHg vs.(129.5±28.9)mmHg, P=0.048). Pearson correlation analysis showed that hyponatremia was negatively correlated with heart rate (r=-0.262, P=0.043), NT-proBNP (r=-0.227, P=0.048), mean pulmonary arterial hypertension (r=-0.259, P=0.046), mean right ventricular pressure (r=-0.296, P=0.047), mean right atria pressure (r=-0.550, P=0.001), systolic right atria pressure (r=-0.552, P=0.001), and diastolic right atria pressure (r=-0.542, P=0.001). Kaplan-Meier survival analysis showed that the 1-year, 2-year and 3-year cumulative survival rates were 76.5%,70.6%,and 64.7% in the hyponatremia group, and 90.3%,86.0%,and 83.9% in the non-hyponatremia group(log-rank test, P=0.036).Multivariate Cox regression analysis showed that hyponatremia was an independent risk factor of death of intermediate-risk pulmonary embolism patient(HR=4.126, 95%CI 1.982-11.343, P=0.036). Conclusion Hyponatremia is associated with adverse hemodynamic and reduced survival in patients with intermediate-risk pulmonary embolism.

A 10 year-old female child developed erythema on the scalp,perioral area,neck,trunk,buttocks,palms and soles within 1 month after birth.Her skin was dry and rough,and the hairs were fine,soft,sparse and easily broken.As age advanced,typical hyperkeratosis and thickening of the skin occurred on an erythematous base.At the age of 5 years,the child developed photophobia and vision impairment.When the child was 8 years old,progressive hearing loss was observed.Physical examination revealed that the height and weight were 109 centimeters and 19 kilograms respectively.Skin examination showed fine,soft,sparse and easily-broken hair,large areas of brown plaques with crusts on the scalp,perioral area,neck,trunk and buttocks,and fissured,purulent and foul-smelling verrucous hyperplasia over these plaques.Brown to black hyperkeratotic plaques were scattered over the extremities,and diffuse hyperkeratosis occurred on the palms and soles.Both fingernails and toenails became thickened,cloudy and white with distal separation and deformation of the nail plate.As ophthalmic examination showed,the patient had photophobia,bilateral bulbar conjunctival hyperemia,corneal opacity and corneal vascular proliferation,and the visual acuity was 0.5 in the left eye and 0.2 in the right eye.Otolaryngological examination revealed moderate binaural sensorineural deafness.Stomatological examination showed enamel hypoplasia and diastema widening.Genetic testing showed a heterozygous mutation (c.C50T) in exon 2 of the gap junction protein beta 2 (GJB2) gene.Based on these clinical manifestations and examinations,the patient was diagnosed with keratitis,ichthyosis,and deafness (KID) syndrome.Skin lesions of the patient were significantly improved after the treatment with oral acitretin.

Objective To construct a eukaryotic expression plasmid of pcDNA 3.1-Ag85A-CD226, and to use it as DNA vaccine then further evaluate its immunogenicity through oral administration in a mouse model.Methods The CD226-PCR2.1-ToPo plasmid was used as the template to clone CD 226 gene by PCR.The CD226 gene was then inserted into pcDNA 3.1-Ag85A plasmid to construct the recombinant plas-mid of pcDNA3.1-Ag85A-CD226.After identified by restriction enzyme analysis and sequencing , the re-combinant plasmid was transfected into HEK 293 cells by using lipofection .The expression of Ag85A-CD226 gene in HEK293 cells was detected by RT-PCR, Western blot and indirect immunofluorescence assay .The purified recombinant plasmid was used to prepare the Ag 85A-CD226 DNA vaccine by liposomal encapsula-tion.The vaccine was administered intragastrically to mice .The activities of NK cells , the cytokine levels in the supernatants of spleen cell cultures and the mRNA level of cytokines in the intestines were evaluated to analyze the immunogenicity of Ag85A-CD226 DNA vaccine.Results The Ag85A-CD226 DNA vaccine was prepared successfully .The expression of Ag85A-CD226 fusion protein was detected in HEK293 cells.The activities of NK cells from mice vaccinated with Ag 85A-CD226 DNA vaccine were higher than those from other control groups (P<0.01).The level of TNF-α, IFN-γand IL-2 in the supernatants of spleen cell cul-tures and in the intestines were significantly up-regulated in comparison with other control groups ( P <0.01).The level of IL-4 in the supernatants of spleen cell cultures was down-regulated in the experimental group (P<0.01), but the level of IL-4 in intestines showed no significant difference among the five groups (P>0.05).Conclusion The Ag85A-CD226 DNA vaccine could significantly enhance Th1 type immune responses systemically and in the intestine as in comparison with those vaccinated with single dose of Ag 85A DNA vaccine or CD226 DNA vaccine.

Objective To investigate the electrocardiogram analysis of electronic colonoscopy on patients with coronary artery heart disease,and to evaluate the safety of colonoscopy on patients with coronary artery heart disease.Methods Sixty patients who underwent colonoscopy from Jun.2012 to Jun.2013 were divided into experimental group (patients with coronary artery heart disease,Heart function class Ⅰ-Ⅲ) and control group (patients without coronary artery heart disease).The changes of electrocardiography during colonoscopy and before performance were compared between two groups through dynamic electrocardiogram.Results Heart rate of the two groups were no statistically significant difference before colonoscopy process (t =0.537,P ＞ 0.05).During the inspection process,there was heart rate increase at different degree in two groups.The heart rate in patients of experiments group was increased from (73.20 ± 7.91) times/min to (88.67 ± 7.79) times/min,which waas more than that in control group (from (73.40 ±6.44) times/min to (74.88 ±7.82) times/min),and the difference between the two groups was significant(t =4.462,P ＜ 0.05).During colonoscopy inspection,the arrhythmia rate arrhythmia in experiment and control group were 46.67％ (14/30),20.00％ (6/30),and the difference was statistically significant (x2 =4.8,P ＜0.05).Meanwhile,ST-T change rates in experimental group and control group were 26.7％ (8/30) and 10.0％ (3/30) (x2 =45.72,P ＜ 0.05).The rate of subjective discomfort the two groups were 40％,30％ (x2 =0.659,P ＞ 0.05).Conclusion During the inspection process of colonoscopy,patients with coronary heart disease are more susceptible to increase heart rate,cardiac arrhythmia,ST-T change than those without coronary heart disease.However,no serious electrocardiographic changes.It is relatively safe to get colonoscopy in patients with coronary heart disease.