ObjectiveDonkey hide is the sole legally designated raw material for the preparation of the traditional Chinese medicine Ejiao. The quality stability of donkey hide during preservation directly determines the efficacy and safety of Ejiao. This study focuses on the dynamic succession of microbial communities during the preservation of donkey hides from different origins, aiming to clarify the correlation between microbial biodiversity difference and the degradation profiles of hide collagen and critical biochemical components, thereby providing a theoretical foundation for developing targeted preservation strategies based on microbial regulation. MethodsDonkey hides originating from four different regions were subjected to an accelerated microbial aging assay to simulate the spoilage process. The microbial community succession was analyzed using high-throughput sequencing. Microstructure changes and pore structure characteristics were assessed by scanning electron microscopy and mercury intrusion porosimetry, respectively. Additionally, the content of major components, including lipids, proteins, and sugars were determined by biochemical methods. ResultsAfter 96 h of aging, the collagen fiber structure in Africa donkey hides (ADH) exhibited significant degradation and collapse, followed by Xinjiang donkey hides (XDH). Instead, the microstructure of Dong’e black donkey hides (DDH) and Peru donkey hides (PDH) remained relatively intact. The porosities of DDH, XDH, PDH, and ADH increased from 27.9%, 15.7%, 30.3%, and 46.2% to 36.5%, 52.6%, 42.8%, and 57.7%, respectively, during the aging process, which suggested that the originally compact fiber structure was disrupted by microbial aging. Fourier transform infrared spectrometer analysis revealed the amide bands in XDH exhibited relatively weak intensity, and no collagen amide I band was observed in ADH. Meanwhile, the lipid and protein contents decreased in all four types of donkey hides, indicating that these components served as the primary nutrient sources for the growth of microorganism. Notably, the most severe collagen degradation was observed in XDH and ADH. A substantial increase was detected in the total soluble sugar in PDH aging solution and hydroxyproline in the ADH aging solution, respectively. These results indicated that donkey hides exhibit distinct patterns of structural degradation and nutrient utilization. Furthermore, the viable cells number of donkey hides increased sharply after 48 h of aging. Metagenomic analysis revealed that the relative abundance of Euryarchaeota in ADH, PDH and XDH declining from initial 93.19%, 97.73% and 30.08% to 0.79%, 1.43% and 0.02% after 96 h, respectively. Conversely, a significantly increase was observed in the abundance of Bacillota, with a marked increase in ADH, peaking at 92.75%. Additionally, the abundance of Pseudomonadota in PDH increased from 0.10% to 87.84%, suggesting that Bacillota and Pseudomonadota may be key factors exacerbating donkey hide spoilage. Unlike the other three types of donkey hides, the dominant bacterial phylum in DDH shifted from Pseudomonadota to Bacteroidota, characterized by a substantial abundance increase of Bacteroidota from 0.13% to 44.22%. ConclusionRegional variation in origin significantly influence the microbial aging of donkey hides, leading to distinct patterns of structural deterioration and differential nutrient utilization. Therefore, implementing origin-specific preservation strategies, through the precisely controlling environmental factors to suppress harmful phyla such as Bacillota and Pseudomonadota, is crucial for enhancing the storage quality of donkey hides.

Objective To investigate the relationship between the comorbidity of dyslipidemia, hypertension and diabetes and lifestyle of adult residents in Hebei Province in 2018, and to provide reference for the development of chronic diseases prevention measures. Methods Using data from the surveillance of chronic diseases and their risk factors among adults in Hebei in 2018, 7 711 permanent residents aged ≥18 years were selected as the research subjects. Multivariate logistic regression analysis was used to analyze the relationship between the comorbidity of dyslipidemia, hypertension, and diabetes and lifestyle in adult residents. Results A total of 7 711 subjects aged ≥18 years were included in 2018. The comorbidity rates of hypertension and dyslipidemia, diabetes and dyslipidemia, and hypertension and diabetes were 16.88%, 7.91%, and 8.13%, respectively. The comorbidity rate of hypertension, diabetes, and dyslipidemia was 22.65%. These comorbidity rates increased with age and BMI. Multivariate logistic regression results showed that male, age, overweight/obesity, physical inactivity, daily sedentary behavior time ≥5 hours, and sleep problems were risk factors for the comorbidity of the "three highs". Conclusion The prevalence of the "three highs" comorbidities is relatively high in Hebei Province, and there are multiple common risk factors. Maintaining a healthy lifestyle and implementing comprehensive prevention and control measures are the key to improving the health level of residents.

Objective To investigate the influencing factors of stroke patients with hypertension and their compliance with antihypertensive drugs, and to provide targeted intervention measures for stroke prevention in hypertensive patients.  Methods Using the method of multi-stage cluster sampling, a total of 59,434 permanent residents aged 40 and above were selected from 48 monitoring sites in 9 cities of Hebei Province from December 2019 to December 2020. Unconditional logistic regression analysis was used to explore the influencing factors of stroke complicated with hypertension and the compliance of patients with antihypertensive drugs.  Results Among the 59 434 subjects, the prevalence rate of stroke was 4.33% and the prevalence rate of stroke complicated with hypertension was 82.47%. The results of univariate analysis showed that the proportion of women, rural areas, dyslipidemia, diabetes, obesity, and people with family history of stroke was higher in stroke patients with hypertension, and the difference was statistically significant (P<0.05). Multivariate logistic regression analysis showed that rural areas, dyslipidemia, diabetes, obesity, and family history of stroke significantly increased the risk of stroke, and the OR (95%CI) values were 1.29 (1.03-1.62), 1.39 (1.12-1.72), 1.58 (1.25-1.99), 1.61 (1.22-2.12) and 1.60 (1.26-2.04), respectively. Among stroke patients with hypertension, 92.71% of patients took antihypertensive drugs. It was found that women's compliance with antihypertensive drugs was good, with an OR (95%CI) value of 1.46 (1.01-2.09).  Conclusion The prevalence rate of stroke complicated with hypertension is high in people aged 40 and above in Hebei Province. Hypertensive people should lower blood lipids, control blood glucose, and lose weight as soon as possible to prevent the occurrence of stroke.

ObjectiveTo investigate the effects of Erchentang （ECD） on the body weight of the mouse model of simple obesity induced by a high-fat diet （HFD） and decipher the underlying mechanisms. MethodsFirstly， single-cell transcriptomics （Sc-RNAseq） was employed to analyze the transcriptional changes in the ileum tissue of mice in the normal group and model group. Then， a mouse model of simple obesity was established with a high-fat diet. The successfully modeled mice were randomly allocated into the following four groups （n=8）： model， low-dose （7.5 g·kg^-1） ECD， medium-dose （15 g·kg^-1） ECD， and high-dose （30 g·kg^-1） ECD. Additionally， 8 mice of the same age were selected as the normal group. The body weight was measured at fixed time points during the 4-week gavage period. The overall efficacy of ECD in alleviating obesity was evaluated through glucose tolerance testing， behavioral analysis， hematoxylin-eosin （HE） staining， and biochemical testing. Protein docking was employed to predict the degree of binding between corresponding proteins. Molecular docking was employed to predict the binding degree between key components of ECD and target proteins. Real-time PCR was employed to determine the mRNA levels of tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， interleukin-1β （IL-1β）， CD68， CD206， zonula occludens-1 （ZO-1）， and Claudin-5 in the ileum. Immunofluorescence staining was used to observe the expression and distribution of Claudin-5 and ZO-1. ResultsThe Sc-RNAseq results indicated that the differentially expressed genes of immune cells in the model group in comparison with the normal group were primarily enriched in biological functions related to lipid metabolism and inflammatory metabolism. Additionally， these genes were associated with the janus kinases（JAK）/signal transducers and activators of transcription （STAT） signaling pathway， an inflammation-related pathway. Compared with the normal group， the model group showed increases in body weight （P<0.01） and blood glucose level （P<0.01）， a decrease in limb strength （P<0.01）， an increase in liver weight （P<0.05）， and elevated serum alanine amino-transferase （ALT） and aspartate transferase （AST） levels （P<0.05， P<0.01）. Additionally， the model group exhibited increased hepatic fat vacuoles， notably enlarged adipocytes in the epididymal and inguinal white adipose tissue， and increased inflammation. Compared with the model group， ECD groups showed reduced body weights （P<0.01） and blood glucose levels （P<0.01）， increased limb strength （P<0.05， P<0.01）， decreased liver weights （P<0.05， P<0.01）， and declined serum ALT and AST levels （P<0.05， P<0.01）. Additionally， ECD reduced hepatic fat vacuoles and the adipocyte volume in the epididymal and inguinal white adipose tissue， and alleviated inflammation. Potential interactions existed between CD68 and ZO-1/Claudin-5， as well as between CD206 and ZO-1/Claudin-5. The key components of ECD， nobiletin， diosmetin， and naringenin， all demonstrated strong binding affinity with the target proteins ZO-1 and Claudin-5. Compared with the normal group， the model group exhibited up-regulated mRNA levels of the pro-inflammatory cytokines TNF-α， iNOS， IL-1β， and CD68 （P<0.05， P<0.01） and down-regulated mRNA levels of the anti-inflammatory cytokine CD206 （P<0.01） and the tight junction proteins Claudin-5 and ZO-1 （P<0.05， P<0.01）. In comparison with the model group， the ECD groups showed down-regulated mRNA levels of TNF-α， iNOS， IL-1β， and CD68 （P<0.05， P<0.01） and up-regulated mRNA levels of CD206， Claudin-5， and ZO-1 （P<0.05， P<0.01）. Compared with the normal group， the model group exhibited down-regulated expression of tight junction proteins Claudin-5 and ZO-1 （P<0.01）. Compared with the model group， ECD groups showed up-regulated expression of Claudin-5 and ZO-1 （P<0.05， P<0.01）. ConclusionECD can significantly ameliorate HFD-induced obesity and excessive body weight gain in mice by improving the inflammatory microenvironment in the ileum and further restoring the integrity of the impaired ileal barrier.

Objective: Miniscrews are commonly utilized as temporary anchorage devices (TADs) in cases of maxillary protrusion and premolar extraction. This study aimed to investigate the effects and potential side effects of two conventional miniscrew configurations on the maxillary incisors. Methods: Eighty-two adult patients with maxillary dentoalveolar protrusion who had undergone bilateral first premolar extraction were retrospectively divided into three groups: non-TAD, two posterior miniscrews only (P-TADs), and two anterior and two posterior miniscrews combined (AP-TADs). Cone-beam computed tomography was used to evaluate the maxillary central incisors (U1). Results: The APTADs group had significantly greater U1 intrusion (1.99 ± 2.37 mm, n = 50) and less retroclination (1.70° ± 8.80°) compared to the P-TADs (–0.07 ± 1.65 mm and 9.45° ± 10.68°, n = 60) and non-TAD group (0.30 ± 1.61 mm and 1.91° ± 9.39°, n = 54).However, the AP-TADs group suffered from significantly greater apical root resorption (ARR) of U1 (2.69 ± 1.38 mm) than the P-TADs (1.63 ± 1.46 mm) and non-TAD group (0.89 ± 0.97 mm). Notably, the incidence of grade IV ARR was 16.6% in the AP-TADs group, significantly higher than the rates observed in the P-TADs (6.7%) and non-TAD (1.9%) groups. Multiple regression analysis revealed that after excluding tooth movement factors, the AP-TADs configuration resulted in an additional 0.5 mm of ARR compared with the P-TADs group. Conclusions In cases of maxillary protrusion and premolar extraction, the use of combined anterior and posterior miniscrews enhances incisor intrusion and minimizes torque loss of the maxillary incisors. However, this approach results in more severe ARR, likely due to the increased apical movement and composite force exerted.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objective: There were associations between emotional abuse and neglect (EAN) and depression, but few studies had tested potential mechanisms underlying these relationships. We aimed to provide insights on how (the mediation role of neuroticism), and under what conditions (the moderator role of psychological resilience), led to a higher level of depression. Methods: This study was a cross-sectional study that used a random cluster sampling method. We randomly selected 3,993 participants from four junior middle schools in northern city of China. Participants were asked to complete four self-reported questionnaires, including the Childhood Trauma Questionnaire, Children Depression Inventory-Short Form, Chinese Big Five Personality Inventory Brief Version, and Chinese Resilience Scale. Results: The results showed that neuroticism mediated the associations between EAN and depression. In addition, the mediating effect of neuroticism was moderated by psychological resilience (p<0.05). Conclusion EAN and neuroticism could have an adverse impact on depression, and psychological resilience could alleviate these negative effects as a moderator. Our model suggested psychological resilience could be a particularly effective intervention point for victims of EAN.

The hippocampus, a major component of the limbic system, is the most important region related to emotion regulation and memory processing. Cognitive impairment and depressive symptoms observed in Alzheimer's disease (AD) patients may be attributed to hippocampal damage caused by amyloid β-protein (Aβ). Our previous studies have demonstrated that a steroid sulfatase inhibitor DU-14 can enhance hippocampal synaptic plasticity and spatial memory abilities in a chronic AD murine model by counteracting the toxic effects of Aβ. However, limited experimental evidence exists regarding the efficacy of steroid sulfatase inhibitor on depressive symptoms in AD animal models. In this study, we investigated the effects of DU-14 on depressive symptoms and theta-band neuronal oscillations in rats with intrahippocampal injection of Aβ_1-42 using various behavioral tests such as sucrose preference test, tail suspension test, forced swimming test, and in vivo hippocampal local field potential (LFP) recording. The results demonstrated that, in comparison to the control group: (1) rats in the Aβ group exhibited a decrease in sucrose preference, indicating a loss of interest in pleasurable activities; (2) rats in the Aβ group displayed aggravated depressive-like behavior characterized by prolonged immobility time during tail suspension and forced swimming tests; (3) Aβ disrupted the induction of theta rhythm via tail pinch stimulation, and resulted in a significant reduction in peak power of theta rhythm. In contrast to the Aβ group, pretreatment with DU-14 resulted in: (1) a significant improvement in Aβ-induced anhedonia, as evidenced by increased sucrose preference; (2) significant alleviation of Aβ-induced despair and depressive-like behaviors, reflected by reduced immobility time during tail suspension and forced swimming tests; (3) successful mitigation of Aβ-mediated inhibition on bilateral hippocampal theta rhythm. These findings indicate that steroid sulfatase inhibitor DU-14 can counteract neurotoxicity induced by Aβ, and prevent Aβ-induced depressive-like behavior and suppression of theta rhythm.
Animals ; Amyloid beta-Peptides/toxicity* ; Rats ; Depression/physiopathology* ; Theta Rhythm/drug effects* ; Hippocampus/physiopathology* ; Male ; Rats, Sprague-Dawley ; Alzheimer Disease/physiopathology* ; Steryl-Sulfatase/antagonists & inhibitors* ; Peptide Fragments ; Behavior, Animal/drug effects*