Functional constipation （FC） is a clinically common functional bowel disorder characterized by a protracted course and associations with various chronic disorders and psychological abnormalities. Although not life-threatening， FC significantly impairs patients' quality of life. FC subtypes include slow-transit constipation （STC）， defecatory disorder （DD）， and normal-transit constipation （NTC）. The pathological mechanisms underlying FC have not been fully elucidated， and overall clinical efficacy remains unsatisfactory. Animal models of FC serve as essential tools for the study of disease mechanisms and the development of novel therapeutics. This article systematically reviews the current state of research on the animal models of FC and identifies that rodents， particularly rats and mice， are the most commonly used species. Dogs and pigs are also employed in complex intervention studies due to their physiological similarities to humans， though their use is limited by housing challenges and ethical considerations. Induction methods vary across different FC subtypes. STC models are primarily established with chemical agents such as loperamide or compound diphenoxylate. DD modeling often involves low-fiber diets combined with methylene blue injection or rectal narrowing. NTC modeling mainly relies on low-fiber dietary interventions. In addition， disease-syndrome combination models based on traditional Chinese medicine （TCM） theory have been developed， encompassing excess patterns such as heat accumulation， cold accumulation， and Qi stagnation， as well as deficiency patterns including Qi deficiency， blood deficiency， Yin deficiency， and Yang deficiency. These are achieved through an approach of disease model + syndrome induction， enabling the integration of mechanisms from both Western and TCM perspectives. Models are evaluated from two aspects： disease and syndrome manifestations （e.g.， colonic transit， secretory function， and TCM syndrome indicators such as mental state and body weight） and disease mechanisms （e.g.， enteric nervous system， interstitial cells of Cajal， smooth muscle cells， gut microbiota， and metabolites）. However， current research still faces challenges such as poor consistency in some models， non-specific interference in mechanism interpretation， insufficient studies on NTC， and lack of TCM tongue and pulse diagnosis in evaluation. Future efforts should focus on optimizing model stability and specificity to provide a more reliable experimental basis for investigating the pathological mechanisms of FC and developing therapeutic agents.

Objective:To explore the role and possible mechanism of ACOT11 in renal fibrosis model mice.Methods:A mouse model of renal fibrosis was established by unilateral ureteral obstruction(UUO)(Sham group and UUO7 group),and the expression of ACOT11 in the kidneys of UUO induced fibrosis mouse models was detected by protein immunoblotting and real-time fluorescence quantitative PCR(qRT-PCR).Subsequently,immunohistochemistry,Masson staining,H&E staining,PAS staining,and other experimental methods were used to detect the expression levels of fibrosis biomarkers fibronectin,α-SMA,and COL-1 in the kidneys of control and experimental group mice.In addition,by constructing ACOT11 gene knockout model mice and using the gene knockout model mice to construct a renal fibrosis model,the expression levels of fibrosis biomarkers such as fibronectin,α-SMA,COL-1,as well as fibrosis mechanism pathway related indicators TGF-β and Smad2 in the kidneys of each group of mice were further detected.Results:The results of WB and qRT-PCR experiments showed that the expression of ACOT11 in the kidney tissue of UUO model mice was significantly reduced compared to the Sham group.After knocking out the ACOT11 gene,H&E staining,PAS staining,and Masson staining showed that pathological inflammatory reactions such as abnormal glomerular and tubular structures,inflammatory cell infiltration and interstitial fibrous tissue proliferation in mice were significantly aggravated compared to the control group,and the expression of fibrosis markers Fibronectin,α-SMA,and COL-1 was significantly higher than that of the control group.Conclusion:ACOT11 plays a protective role in mice with unilateral ureteral obstruction model.After ACOT11 gene knockout,the fibrosis biomarkers of the mouse kidney increases and the degree of fibrosis worsens.

BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular disease in previous studies. However, it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease (CHD). Therefore, the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people. METHODS: 19,194 participants aged ≥ 60 years who had three AIP measurements between 2018 and 2020 were included in this study. AIP was defined as log₁₀ (triglyceride/high-density lipoprotein cholesterol). The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020. Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI of CHD events between different trajectory groups from 2020 to 2023. RESULTS: Three different trajectory patterns were identified through group-based trajectory model: the low-level group (n = 7410, mean AIP: -0.25 to -0.17), the medium-level group (n = 9981, mean AIP: 0.02-0.08), and the high-level group (n = 1803, mean AIP: 0.38-0.42). During a mean follow-up of 2.65 years, a total of 1391 participants developed CHD. After adjusting for potential confounders, compared with the participants in the low-level group, the HR with 95% CI of the medium-level group and the high-level group were estimated to be 1.24 (1.10-1.40) and 1.43 (1.19-1.73), respectively. These findings remained consistent in subgroup analyses and sensitivity analyses. CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly. This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective:To explore the effects and mechanisms of Shen-su-yin (SSY) on acute lung injury (ALI) in rats based on untargeted Metabolomics, network pharmacology, and experimental verification.Methods:Untargeted Metabolomics was performed to detect the ingredients of SSY by using ultra-high performance liquid chromatography-Q-exactive orbitrap mass spectrum, and the active ingredients were screened from the detected ingredients. Common targets of the active ingredient targets and ALI targets were utilized to screen hub targets to perform gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. Then, key hub targets were selected from the hub targets, and the active ingredients-hub targets network was built to screen core ingredients. Subsequently, molecular docking was performed between the key hub targets and the core ingredients. 48 rats were randomly and equally divided into 4 groups by using a random number table: normal control group, lipopolysaccharide-induced ALI group, ALI+SSY group, and ALI+dexamethasone group. 24 hours after lipopolysaccharide induction, the levels of respiratory rate, blood lactate, lung wet/dry weight ratio, ALI score, inflammatory factors of bronchoalveolar lavage fluid, and oxidative stress mediators of lung tissue in each group were evaluated, and the expression of phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-glycogen synthase kinase (GSK) 3β-nuclear factor erythroid 2-related factor 2 (Nrf2)/nuclear factor (NF)-κB signaling pathway was also detected by using Western blot. Finally, one-way analysis of variance, Welch test, or Kruskal-Wallis H test was used to compare data differences among groups. Results:A total of 415 ingredients were detected from the SSY. 66 of the detected ingredients were identified as active ingredients, and 10 of them were selected as core ingredients. The number of common targets, hub targets, and key hub targets was 337, 50, and 10, respectively. Total of 285 biological processes, 32 cellular components, and 51 molecular functions were enriched though GO analysis, and 148 cell signaling pathways such as pathways in cancer and PI3K-AKT signaling pathway were enriched though KEGG analysis. Molecular docking studies revealed that all binding energies between the 10 key hub targets and the 10 core ingredients were less than -5 kcal/mol. Compared with the ALI group, the levels of the respiratory rate, blood lactate, and lung wet/dry weight ratio in ALI+SSY group were significantly decreased (all P<0.01), and the level of ALI score showed a downward trend, but the difference was not statistically significant ( P>0.05). In addition, the levels of interleukin-6, interleukin-1β, and tumor necrosis factor-α in bronchoalveolar lavage fluid and the levels of malondialdehyde, protein carbonyl, and 8-hydroxy-2-deoxyguanosine in lung tissue of rats in ALI+SSY group were significantly decreased in comparison with those in ALI group (all P<0.01). Moreover, compared with the ALI group, the phosphorylation levels of PI3K p85α, AKT1, and GSK3β and the expression level of Nrf2 in lung tissue of ALI+SSY group were significantly up-regulated (PI3K p85α phosphorylation and AKT1 phosphorylation, P<0.01; GSK3β phosphorylation and Nrf2, P<0.05), while the phosphorylation level of NF-κB p65 was significantly down-regulated ( P<0.01). Conclusions:Active ingredients detected from SSY via untargeted Metabolomics can inhibit oxidative stress and inflammation in ALI rats by regulating the PI3K-AKT-GSK3β-Nrf2/NF-κB signaling pathway, thereby alleviating lung lesions.

Objective:To describe the prevalence of non-alcoholic fatty liver disease (NAFLD) in people living with HIV in Taizhou, Zhejiang Province, and identify the factors associated with NAFLD in this population.Methods:A cross-sectional survey was conducted from 2021 to 2023. Based on the routine follow-up management of people living with HIV, liver ultrasound examination, physical examination and laboratory test were conducted to collect the information about the diagnosis of NAFLD and biochemical indicators in this population. Logistic regression model was used to identify the factors associated with the prevalence of NAFLD.Results:In the 2 550 study participants, the prevalence of NAFLD was 21.5% (548/2 550), abnormal liver function was found in 23.7% (604/2 550) of the study participants, and liver fibrosis was found in 45.2% (1 152/2 550) of the study participants. Multivariable logistic regression analyses showed that being women (a OR=0.55, 95% CI: 0.42-0.73), being overweight or obese (a OR=3.22, 95% CI: 2.59-4.01), having diabetes (a OR=3.37, 95% CI: 2.15-5.29), having dyslipidemia (a OR=2.96, 95% CI: 2.25-3.89), CD4 + T lymphocyte (CD4) counts <200 cells/μl (a OR=0.61, 95% CI: 0.42-0.88), and receiving Efavirenz (EFV) + Lamivudine (3TC) + Zidovudine (AZT) for antiretroviral therapy (ART)(a OR=1.52, 95% CI: 1.17-1.98) were associated with NAFLD. NAFLD was positively associated with abnormal liver function (a OR=2.01, 95% CI: 1.60-2.52) and inversely associated with liver fibrosis (a OR=0.76, 95% CI: 0.59-0.98). The 45-59 age group (a OR=7.05, 95% CI: 5.65-8.80), CD4 counts <200 cells/μl (a OR=1.45, 95% CI: 1.06-1.97) and receiving Nevirapine (NVP)+3TC+AZT of ART (a OR=1.87,95% CI: 1.44-2.43) were the main factors associated with liver fibrosis. Conclusions:The prevalence of NAFLD in people living with HIV Taizhou was more than 20.0%, with a significant proportion of them having abnormal liver function and liver fibrosis. Being overweight or obese, suffering from diabetes, having dyslipidemia, low CD4 counts, and receiving specific ART were associated with NAFLD. NAFLD, CD4 counts and specific ART were the main factors associated with abnormal liver function and liver fibrosis.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

BACKGROUND:Non-traumatic necrosis of the femoral head is a difficult joint disease,and preserving one's own femoral head is of great significance for young patients.Currently,there is a lack of regular and unified functional exercise plans.OBJECTIVE:To investigate the effect of hip abductor muscle exercise on the three-dimensional gait and collapse rate of patients with non-traumatic femoral head necrosis,and to provide theoretical basis for effective rehabilitation of patients with non-traumatic femoral head necrosis.METHODS:Totally 81 non-traumatic and non-surgical patients with femoral head necrosis(81 hips)admitted to the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from June 2020 to June 2022 were included.Patients were randomly divided into a control group(n=40)and a hip abductor muscle exercise group(n=41).The control group received routine physical therapy and medication treatment.The hip abductor muscle exercise group underwent hip abductor muscle exercise on the basis of the control group.The gait status(hip joint range of motion,step length difference,and ground contact time difference)of two groups of patients was evaluated using the Tecnobody balance assessment system before and 12 weeks after treatment.The BIODEX-S4 isokinetic muscle strength testing system was used to test the peak force distance of hip abduction isokinetic muscle strength.Gluteus medius width ratio was compared between two groups.The collapse rate was compared between two groups of patients 1 year after treatment.RESULTS AND CONCLUSION:(1)There was no statistically significant difference between the hip abductor muscle exercise group and the control group in terms of age,gender,side profile,body mass index,and etiology(P＞0.05).(2)Before treatment,there was no significant statistical difference in the range of motion of the affected hip joint between the two groups(P＞0.05).After treatment,the range of motion of the affected hip joint in both groups improved compared to before treatment(P＜0.05),and the range of motion of the affected hip joint in the hip abductor muscle exercise group was significantly higher than that in the control group(P＜0.05).(3)Before treatment,there was no significant statistical difference in the step length and touchdown time between the two groups(P＞0.05).12 weeks after treatment,the difference in step length and touchdown time between the two groups decreased compared to before treatment(P＜0.05),and the difference in step length and touchdown time between the hip abductor muscle exercise group after treatment was significantly greater than that of the control group(P＜0.05).(4)Before treatment,there was no significant statistical difference in gluteus medius width ratio between the two groups(P＞0.05).12 weeks after treatment,the gluteus medius width ratio of both groups increased compared to that before treatment(P＜0.05),and the gluteus medius width ratio of the hip abductor muscle exercise group was significantly higher than that of the control group(P＜0.05).(5)At 1 year after treatment,the comparison of femoral head collapse rates between the two groups showed significant statistical significance(P＜0.05),and that in the hip abductor muscle exercise group(22％)was significantly lower than that in the control group(45％).(6)It is concluded that exercise of the hip abductor muscle effectively enhances hip joint function,improves gait,and reduces the rate of femoral head collapse in patients with non-traumatic femoral head necrosis.It is recommended to use hip abductor muscle exercise as one of the basic methods for hip preservation in non-traumatic femoral head necrosis.

Objective To investigate the carrying status and drug resistance analysis of pathogenic bacteria in the gut of healthy population in Huadu District,Guangzhou,and provide reference for epidemiological re-search.Methods A total of 337 459 anal swabs were directly isolated and cultured from healthy individuals who underwent physical examinations from 2018 to 2023.600 anal swabs from 2022 were randomly selected for multi pathogen nucleic acid testing,direct isolation and culture,and enrichment culture.Identification of bacteria was conducted by using VITEK 2 Compact and VITEK MS,serological testing was used for determi-nation of type,and drug susceptibility testing of pathogenic bacteria was conducted.Results A total of 128 pathogenic bacteria were isolated from rectal swabs,including 52 strains of Salmonella,71 strains of Aero-monas,3 strains of Vibrio parahaemolyticus,and 2 strains of Shigella flexneri,with a total detection rate of 3.79/10 000.The detection rate of Salmonella in direct isolation and culture of 600 rectal swabs was 0.50％,the detection rate of enrichment culture was 1.00％,and the detection rate of multi-pathogen nucleic acid de-tection was 1.17％.52 strains of Salmonella were divided into 27 serotypes,and Salmonella Ⅰ 4,5,12:i:—was the dominant serotype.Aeromonas sobria was the dominant serotype in Aeromonas.The sensitivity of Salmonella to piperacillin/tazobactam,imipenem,cefepime,levofloxacin,and aztreonam was up to 92.00％or more,however,the phenomenon of multidrug resistance was severe,with a multidrug resistance rate as high as 40.38％.The resistance rate of Aeromonas to ampicillin and ampicillin/sulbactam was up to 85.00％or more,while Aeromonas was relatively sensitive to other antibiotics.Conclusion There are many species and types of intestinal pathogenic bacteria carried by healthy individuals in Huadu District,Guangzhou,with Aero-monas and Salmonella ranking first and second,and levofloxacin treatment could be preferred.The use of bac-terial culture and multi pathogen nucleic acid testing methods could improve the detection rate of intestinal pathogenic bacteria,and attention should be paid to the monitoring of intestinal pathogenic bacteria among rel-evant practitioners.

Objective:To study the risk factors and the molecular epidemiology characteristics for Carbapenem-resistant Enterobacteriaceae(CRE) colonization in neonatal inpatients in Shenzhen region, China, which provide reference for the prevention and control of clinical CRE infection.Methods:This study is a prospective case-control study.Anal samples from inpatients between January 2023 and December 2023 at Longgang Maternity and Child Institute of Shantou University Medical College and Shenzhen Children's Hospital were collected for screening CRE strain. Drug susceptibility test, modified Carbapenem Inactivation Method (mCIM) test, drug resistance-related gene sequencing and multilocus sequence typing (MLST) were performed for isolated CRE strains.Meanwhile, the clinical data were collected for analyzing the risk factors of CRE intestinal colonization by multivariate regression analysis.Results:A total of 1 517 patients were screened, 26 CRE(1.7%, 26/1 517) were identified which including 14 Escherichia coli(53.8%, 14/26), 11 Klebsiella pneumoniae(42.3%, 11/26), 1 Enterobacter cloacae(3.9%, 1/26). The predominant carbapenemase gene was New Delhi Metallo(NDM) (92.4%, 24/26), followed by Imipenem (IMP) (3.8%, 1/26) and Guiana extended spectrum gene (GES) (3.8%, 1/26).Among the carried NDM resistance genes, New Delhi Metallo 5 (NDM5) was the main one, accounting for 84.6% (22/26).The MLST typing of Escherichia coli was mainly Sequence Type 48 (ST48) (6/14), while that of Klebsiella pneumoniae was mainly Sequence Type 35 (ST35) (10/11). All CRE isolates were resistant to penicillin, penicillinase inhibitors, cephalosporins, ertapenem and imipenem.The resistance rates of Escherichia coli to amikacin, levofloxacin was 1/14, 4/14, respectively. All isolates of Klebsiella pneumoniae were sensitive to amikacin, and the resistance rate to levofloxacin is 1/11. Risk factors for CRE colonization include the older age, length of hospital stay, tracheal intubation, invasive respiration, lumbar puncture, Apgar <7 score, and exposure to antibiotics.Conclusions:NDM5 is the predominant resistant gene in CRE isolated from neonatal patients feces in Shenzhen region.It is necessary to strengthen the screening of CRE colonization in neonate for prevention and control of CRE infection.