Object To study the efficacy and potential mechanism of Tongbianling capsule in constipation. Methods The effects of Tongbianling capsule on intestinal motility in normal mice and carbon powder propulsion rate in small intestine of constipation model mice after were observed administration. The potential targets and key pathways of Tongbianling capsule in treating constipation were identified through network pharmacology. To verify the mechanism, the expression of p-PI3K/PI3K, p-AKT/AKT and CASP3 proteins in mouse colon tissue was detected by the western blot. Results The time for mice to excrete the first black stool was shortened and the number of fecal particles was increased in Tongbianling capsule administration group, and the carbon powder propulsion rate of mice in each Tongbianling capsule administration group was increased. The results of network pharmacology showed that treatment of constipation by Tongbianling capsule may be related to signaling pathways such as PI3K-Akt signaling pathway and 5-HT. The protein expression of p-PI3K/PI3K, p-AKT/AKT, and CASP3 in mouse colon tissue could be significantly downregulated in administration group. Conclusion Tongbianling capsule could effectively promote intestinal peristalsis in mice, increase the frequency of defecation, and effectively treat constipation. The mechanism of its action may be related to the direct or indirect regulation of intestinal motility by the PI3K-Akt signaling pathway.

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that severely affects the health of the elderly, marked by its incurability, high prevalence, and extended latency period. The current approach to AD prevention and treatment emphasizes early detection and intervention, particularly during the pre-AD stage of mild cognitive impairment (MCI), which provides an optimal “window of opportunity” for intervention. Clinical detection methods for MCI, such as cerebrospinal fluid monitoring, genetic testing, and imaging diagnostics, are invasive and costly, limiting their broad clinical application. Speech, as a vital cognitive output, offers a new perspective and tool for computer-assisted analysis and screening of cognitive decline. This is because elderly individuals with cognitive decline exhibit distinct characteristics in semantic and audio information, such as reduced lexical richness, decreased speech coherence and conciseness, and declines in speech rate, voice rhythm, and hesitation rates. The objective presence of these semantic and audio characteristics lays the groundwork for computer-based screening of cognitive decline. Speech information is primarily sourced from databases or collected through tasks involving spontaneous speech, semantic fluency, and reading, followed by analysis using computer models. Spontaneous language tasks include dialogues/interviews, event descriptions, narrative recall, and picture descriptions. Semantic fluency tasks assess controlled retrieval of vocabulary items, requiring participants to extract information at the word level during lexical search. Reading tasks involve participants reading a passage aloud. Summarizing past research, the speech characteristics of the elderly can be divided into two major categories: semantic information and audio information. Semantic information focuses on the meaning of speech across different tasks, highlighting differences in vocabulary and text content in cognitive impairment. Overall, discourse pragmatic disorders in AD can be studied along three dimensions: cohesion, coherence, and conciseness. Cohesion mainly examines the use of vocabulary by participants, with a reduction in the use of nouns, pronouns, verbs, and adjectives in AD patients. Coherence assesses the ability of participants to maintain topics, with a decrease in the number of subordinate clauses in AD patients. Conciseness evaluates the information density of participants, with AD patients producing shorter texts with less information compared to normal elderly individuals. Audio information focuses on acoustic features that are difficult for the human ear to detect. There is a significant degradation in temporal parameters in the later stages of cognitive impairment; AD patients require more time to read the same paragraph, have longer vocalization times, and produce more pauses or silent parts in their spontaneous speech signals compared to normal individuals. Researchers have extracted audio and speech features, developing independent systems for each set of features, achieving an accuracy rate of 82% for both, which increases to 86% when both types of features are combined, demonstrating the advantage of integrating audio and speech information. Currently, deep learning and machine learning are the main methods used for information analysis. The overall diagnostic accuracy rate for AD exceeds 80%, and the diagnostic accuracy rate for MCI also exceeds 80%, indicating significant potential. Deep learning techniques require substantial data support, necessitating future expansion of database scale and continuous algorithm upgrades to transition from laboratory research to practical product implementation.

Objective To analyze the trend of global cellulitis disease burden from 1990 to 2019, and to provide a theoretical basis for the prevention and control of cellulitis disease. Methods The Global Burden of Disease 2021 (GBD2021) data were collected, and data on the incidence, mortality, and disability-adjusted life year (DALY) of cellulitis were analyzed for each country worldwide. The estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trend change of cellulitis from 1990 to 2021. Results The global burden of cellulitis increased significantly in 2021, with 55.96 million cases, 28.9 million deaths and 876.1 million DALYs, respectively. Incidence and mortality rates were generally higher in males than in females. The incidence and DALYs were higher in high SDI regions, with the highest burden observed in South Asia. In contrast, East Asia exhibited the lowest burden and demonstrated a declining trend. There were significant differences between countries, with India having the highest prevalence, the United States having the highest incidence, and Bahrain having the fastest growing rate.In 2021, China had the lowest age-standardised incidence of cellulitis in the world and the fastest declining age-standardised incidence and age-standardised DALYs. Conclusion The global disease burden of cellulitis is increasing from 1990-2021, and cellulitis remains an an important global public health problem. Targeted preventive meausres should be taken in areas with different economical levels. Men, middle-aged and elderly people, and newborns are the key groups in need of attention and health education.

BACKGROUND: Enzalutamide, a second-generation androgen receptor (AR) pathway inhibitor, is widely used in the treatment of castration-resistant prostate cancer. However, after a period of enzalutamide treatment, patients inevitably develop drug resistance. In this study, we characterized leucine-rich repeated G-protein-coupled receptor 5 (LGR5) and explored its potential therapeutic value in prostate cancer. METHODS: A total of 142 pairs of tumor and adjacent formalin-fixed paraf-fin-embedded tissue samples from patients with prostate cancer were collected from the Pathology Department at Sun Yat-sen Memorial Hos-pital. LGR5 was screened by sequencing data of enzalutamide-resistant cell lines combined with sequencing data of lesions with different Gleason scores from the same patients. The biological function of LGR5 and its effect on enzalutamide resistance were investigated in vitro and in vivo . Glutathione-S-transferase (GST) pull-down, coimmunoprecipitation, Western blotting, and immunofluorescence assays were used to explore the specific binding mechanism of LGR5 and related pathway changes. RESULTS: LGR5 was significantly upregulated in prostate cancer and negatively correlated with poor patient prognosis. Overexpression of LGR5 promoted the malignant progression of prostate cancer and reduced sensitivity to enzalutamide in vitro and in vivo . LGR5 promoted the phosphorylation of glycogen synthase kinase-3β (GSK-3β) by binding heat shock protein 90,000 alpha B1 (HSP90AB1) and mediated the activation of the Wingless/integrated (WNT)/β-catenin signaling pathway. The increased β-catenin in the cytoplasm entered the nucleus and bound to the nuclear AR, promoting the transcription level of AR, which led to the enhanced tolerance of prostate cancer to enzalutamide. Reducing HSP90AB1 binding to LGR5 significantly enhanced sensitivity to enzalutamide. CONCLUSIONS LGR5 directly binds to HSP90AB1 and mediates GSK-3β phosphorylation, promoting AR expression by regulating the WNT/β-catenin signaling pathway, thereby conferring resistance to enzalutamide treatment in prostate cancer.
Male ; Humans ; Phenylthiohydantoin/pharmacology* ; Benzamides ; Receptors, G-Protein-Coupled/genetics* ; Nitriles ; Cell Line, Tumor ; HSP90 Heat-Shock Proteins/metabolism* ; Drug Resistance, Neoplasm/genetics* ; Prostatic Neoplasms/drug therapy* ; beta Catenin/metabolism* ; Receptors, Androgen/genetics* ; Animals ; Mice ; Wnt Signaling Pathway/physiology*

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Munchausen syndrome by proxy（MSBP）in children refers to the caregivers who enforce unnecessary medication-seeking on children by falsifying symptoms or inducing disease（exacerbation），resulting in different degrees of physical or mental damage.And it may lead to adverse psychosocial consequences of the victims in adulthood，and even become the new "MSBP caregivers".First reported in 1977，MSBP in children has attracted widespread attention in European and American countries，and gradually attracted attention worldwide.However，Chinese pediatricians have insufficient knowledge of the disease at present，and there are just a few relevant literature reports in China.This article reviews the clinical features and progress on diagnosis and treatment of MSBP in children.

Objective:To establish a graded method to avoid mean fluorescence intensity(MFI)threshold of HLA Class I antibodies corresponding antigen,and the HLAMatchmaker program has been used to select the minimum mismatch value of donor-patient epitopes.Evaluate the application value of combining both methods in selecting HLA compatible platelets(PTL)for patients with immune platelet transfusion failure(IPTR)in improving platelet the corrected count increment(CCI).Methods:A total 7 807 PLT cross-matching compatible were performed by the solid-phase red cell adherence(SPRCA)method for 51 IPTR patients.The Luminex single antigen flow cytometry was used to detect HLA Class I antibodies in patients,and detected the MFI value for different specificity antigens of HLA Class I antibodies,was graded into strong positive group(MFI＞4 000,level 1),medium positive group(1 000＜MFI 4 000,2),weak positive group(500＜MFI≤1 000,3),and one negative control group(MFI≤500).The results of 7 807 SPRCA their negative/positive reaction wells were enrolled and statistically analyzed in different grades and the four groups,the statistical differences between the four groups were compared.Multiple applications for the select HLA Class I compatible donor events were made for patients in two cases,and HLAMatchmaker program was used to calculate the number of HLA Class I epitopes mismatches between the donors and patients.The donor with the minimum number of epitopes mismatches was selected,while avoiding the corresponding antigens of HLA Class I antibodies in levels 1 and 2,the provision of HLA compatible platelets for IPTR.After the transfusions,the CCI value of the platelet transfusion efficacy evaluation index was calculated,and the clinical evaluation of the transfusion effect was obtained through statistical analysis.Results:There were statistically significant differences in the positive results of SPRCA immunoassay among the strong positive group,medium positive group,and weak positive group of 51 IPTR patients with different specific of HLA-I class antibodies and corresponding antigens(all P＜0.001).The positive results showed a range from high to low,with strong positive group＞medium positive group＞weak positive group.There were a statistical difference among between the strongly positive or moderately positive groups and the negative control group(P＜0.001).There was no statistical difference between the weakly positive group and the negative control group(P＞0.05).The strong positive group was set as the corresponding specific HLA Class I site corresponding antigen grade 1 avoidance threshold,the medium positive group as the grade 2 avoidance thresholds,and the weak positive group as the grade 3 avoidance threshold.In the case of donor platelet shortage,it is not necessary to avoid the weak positive group.Avoiding the strategy of donor antigens and HLAMatchmaker program scores≤7 corresponding to HLA Class I antibodies of levels 1 and 2,with CCI values＞4.5 × 109/L within 24 hours,can obtain effective clinical platelet transfusion conclusions.Conclusion:When selecting HLA Class I compatible donors for IPTR patients,the grading avoids HLA Class I antibodies corresponding to donor antigens,and the donor selection strategy with the minimum scores of HLAMatchmaker program is comprehensively selected.The negative result confirmed by platelet cross-matching experiments has certain practical application value for improving platelet count in IPTR patients.

Objective:To analyze the risk factors for the development of moderate to severe liver fibrosis in male metabolic syndrome (MetS) patients.Methods:In this study, a single-center retrospective study was conducted to select 414 male patients with MetS who were diagnosed by physical examination at the First Affiliated Hospital of Zhengzhou University from January 2022 to November 2023. The patients were classified into MetS with no/slight hepatic fibrosis group (MetS F0-1 group, 294 cases) and MetS with moderate to severe hepatic fibrosis group (MetS F2-4 group, 120 cases) according to the results of liver hardness test. The independent risk factors for the development of moderate-to-severe liver fibrosis in male MetS patients were explored by univariate and multivariate analyses of whether they had diabetes, and the levels of body mass index (BMI), serum glutamate aminotransferase (ALT), aspartate aminotransferase (AST), glutamyltransferase (GGT), and uric acid.Results:Compared with the MetS F0-1 group, theMets F2-4 group had the characteristics of high obesity rate, high diabetes rate and high serum ALT, AST. GGT and uric acid levels (all P<0.05). One-way regression analysis revealed that those with diabetes mellitus ( OR=2.891, 95% CI: 1.627-5.138), high BMI ( OR=1.276, 95% CI: 1.191-1.368), high level of serum ALT ( OR=1.024, 95% CI: 1.015-1.034), AST ( OR=1.052, 95% CI: 1.032-1.072), GGT ( OR=1.011, 95% CI: 1.005-1.016) and uric acid ( OR=1.003, 95% CI: 1.001-1.006) were the risk factors for the development of moderate-to-severe hepatic fibrosis in male patients with MetS, whereas a multifactorial regression analysis found that the presence of diabetes ( OR=5.561, 95% CI: 2.706-11.428), high BMI ( OR=1.271, 95% CI: 1.177-1.372) and high serum uric acid ( OR=1.004, 95% CI: 1.001-1.007) were the independent risk factors for the development of moderate-to-severe hepatic fibrosis in male MetS patients. Conclusion:Diabetes, high BMI and high level of serum uric acid are independent risk factors for the development of moderate-to-severe hepatic fibrosis in male patients with MetS.

Objective To investigate the risk factors of microcirculation obstruction(MVO)after reperfusion in patients with acute myocardial infarction(AMI).Methods Forty-one patients with AMI who received treatment with myocardial reperfusion were retrospectively selected.Cardiac magnetic resonance(CMR)was used to determine whether the patients had MVO.The patients were divided into MVO and non-MVO groups.The basic data,laboratory examination and CMR parameters of patients were collected and compared between the groups,and the risk factors related to MVO were screened out by logistic regression analysis.Results Delayed myocardial enhancement was observed in all 41 patients,among which 11 cases(26.8%)were with MVO.A total of 206 delayed myocardial enhancement segments were observed,of which 77 segments combined with MVO and 129 segments without MVO.AMI patients with MVO had a higher rate of transmural myocardial infarction,greater infarct volume,left ventricular myocardial mass(LVMM)and edema degree,as well as lower ejection fraction of left and right ventricles(P<0.05).Multivariate logistic regression analysis indicated that infarct volume[odds ratio(OR)=1.116,95%confidence interval(CI)1.017-1.224,P=0.020]was an independent risk factor for MVO after AMI reperfusion.Conclusion Infarct volume is an independent risk factor for MVO after AMI reperfusion,and MVO is associated with left and right ventricular function impairment.