The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

Primary biliary cholangitis （PBC） is a chronic progressive autoimmune liver disease that is often comorbid with other connective tissue diseases （CTDs）， and such comorbidity can significantly alter the natural course or clinical phenotype of PBC or CTDs， limiting available therapeutic drugs and complicating clinical decision-making. Due to the involvement of the interdisciplinary subjects of hepatology， rheumatology， and clinical immunology and a paucity of large-scale cohort data and in-depth basic research， there is a limited understanding of such comorbidity in clinical practice， which increases the complexity of clinical diagnosis and treatment. This article summarizes the comorbidity of PBC with common CTDs such as Sjögren’‍s syndrome， systemic sclerosis， systemic lupus erythematosus， and idiopathic inflammatory myopathies， and analyzes related immune mechanisms， clinical manifestations， diagnostic challenges， treatment strategies， and prognosis. It is expected to establish PBC-CTD comorbidity cohorts through future multidisciplinary collaborations， focus on genetic background， immune mechanisms， and multi-omics approaches， elucidate pathogenesis and novel therapeutic targets， and improve the prognosis of patients by optimizing treatment strategies through precision medicine and artificial intelligence.

Objective To quantitatively assess the association of short-term exposure to polycyclic aromatic hydrocarbons (PAHs) in ambient fine particulate matter (PM2.5) with residents mortality. Methods A time-stratified case-crossover study was conducted from 2020 to 2022 among 10606 non-accidental residents by using the Guangzhou Cause of Death Surveillance System in Conghua District, Guangzhou. Exposure levels of PAHs in PM_2.5 and meteorological data during the study period were obtained from the Center for Disease Control and Prevention in Conghua District and the China Meteorological Administration Land Data Assimilation System (CLDAS-V2.0), respectively. Conditional Poisson regression model was used to estimate the exposure-response association between PAHs and the mortality risk. Results Fluoranthene, chrysene, benzo[k]fluoranthene, benzo[a]pyrene, and indeno[1,2,3-cd]pyrene were significantly associated with an increased risk of mortality. For every one interquartile range increase in exposure levels, the non-accidental mortality risks increased by 8.33% (95% CI: 1.80%, 15.27%), 4.67% (95% CI: 1.86%, 7.57%), 6.07% (95% CI: 2.08%, 10.21%), 4.62% (95% CI: 1.85%, 7.47%), and 4.70% (95% CI: 0.53%, 9.03%), respectively. The estimated non accidental deaths attributable to exposure to fluoranthene, chrysene, benzo[k]fluorine, benzo[a]pyrene and indine[1,2,3-cd]pyrene were 5.91%, 6.08%, 6.51%, 6.46%, and 4.21%, respectively. Conclusions Short-term exposure to PAHs in PM_2.5, including fluoranthene, chrysene, benzo[k]fluoranthene, benzo[a]pyrene and indine[1,2,3-cd]pyrene, was significantly associated with an increased risk of mortality among residents.

This study explores the mechanism of Guben Jiannao Liquid on Alzheimer's disease(AD) by regulating autophagy based on the liver kinase B1(LKB1)/adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) pathway. Male SD rats were randomly divided into the blank group, model group, low-dose and high-dose groups of Guben Jiannao Liquid, and rapamycin group, with 10 rats in each group. Except for the blank group, all other groups of rats were injected bilaterally in the hippocampus with β-amyloid(Aβ)_(1-42) to establish the AD model. The low-dose(6.21 g·kg~(-1)) and high-dose(12.42 g·kg~(-1)) groups of Guben Jiannao Liquid and rapamycin group(1 mg·kg~(-1)) were given the corresponding drugs by gavage, and the blank and model groups were given an equal volume of saline by gavage for four weeks. Morris water maze was used to test the learning and memory ability of rats in each group; hematoxylin-eosin(HE) and Nissl staining were used to observe the morphological and quantitative changes of neurons and Nissl bodies in the CA1 region of rat hippocampus; immunohistochemistry was utilized to detect Aβ-positive cell expression in the CA1 region of rat hippocampus; transmission electron microscopy was employed to observe ultrastructural changes in rat hippocampal tissue, and Western blot was used to examine the protein expression levels of LKB1, p-AMPK/AMPK, p-mTOR/mTOR, Beclin1, p62, and LC3-Ⅱ in the hippocampal tissue of the rats. The results showed that compared with those in the blank group, rats in the model group had elevated evasion latency and decreased number of platform transversal and residence time in the platform quadrant. The number of neurons in the hippocampal area was reduced, and the morphology was impaired. The average integral optical density value of Aβ-positive cells was elevated; the expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were decreased, and the expression levels of p-mTOR/mTOR and p62 were increased. Compared with those in the model group, rats in the low-dose and high-dose groups of Guben Jiannao Liquid had shorter evasion latency, higher number of platform transversal, longer residence time in the platform quadrant, increased number of neurons, decreased expression of Aβ-positive cells and average integral optical density values, and increased number of autophagic lysosomes in hippocampal tissue. The expression levels of LKB1, Beclin1, and LC3-Ⅱ were elevated in the hippocampus of rats in the low-dose group of Guben Jiannao Liquid. The expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were elevated in the hippocampal tissue of rats in the high-dose group of Guben Jiannao Liquid, and the expression levels of p-mTOR/mTOR and p62 were decreased. The findings suggest that Guben Jiannao Liquid can improve cognitive impairment in AD rats, and its mechanism of action may be related to the activation of the LKB1/AMPK/mTOR signaling pathway and the up-regulation of autophagy level.
Animals ; Alzheimer Disease/physiopathology* ; Male ; TOR Serine-Threonine Kinases/genetics* ; Autophagy/drug effects* ; Rats, Sprague-Dawley ; Protein Serine-Threonine Kinases/genetics* ; AMP-Activated Protein Kinases/genetics* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; AMP-Activated Protein Kinase Kinases ; Humans ; Hippocampus/metabolism*

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*

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

OBJECTIVE: To explore decompression strategies for lateral lumbar spinal stenosis under unilateral biportal endoscopy (UBE) assistance. METHODS: A clinical data of 86 patients with lateral lumbar stenosis treated with UBE-assisted intervertebral decompression between September 2022 and December 2023 was retrospectively analyzed. There were 42 males and 44 females with an average age of 63.6 years (range, 45-79 years). The disease duration ranged from 6 to 14 months (mean, 8.5 months). Surgical levels included L _{2, 3} in 3 cases, L _{3, 4} in 26 cases, L _{4, 5} in 42 cases, and L ₅, S ₁ in 15 cases. According to Lee's grading system, there were 21 cases of grade 1, 37 cases of grade 2, and 28 cases of grade 3 for lumbar spinal stenosis. Based on the location of stenosis and clinical symptoms, the 33 cases underwent interlaminar approach, 7 cases underwent interlaminar approach with auxiliary third incision, 26 cases underwent contralateral inclinatory approach, and 20 cases underwent paraspinal approach; then, the corresponding decompression procedures were performed. Visual analogue scale (VAS) score was used to evaluate lower back/leg pain before operation and at 1 and 3 months after operation, while Oswestry disability index (ODI) was used to evaluate spinal function. At 3 months after operation, the effectiveness was evaluated using the modified MacNab evaluation criteria. The spinal stenosis and decompression were evaluated based on Lee's grading system using lumbar MRI before operation and at 3 months after operation. RESULTS: All procedures were successfully completed with mean operation time of 95.1 minutes (range, 57-166 minutes). Dural tears occurred in 2 cases treated with interlaminar approach with auxiliary third incision. All incisions healed by first intention. All patients were followed up 3-10 months (mean, 5.9 months). The clinical symptoms of the patients relieved to varying degrees. The VAS scores and ODI of lower back and leg pain at 1 and 3 months after operation significantly improved compared to preoperative levels ( P<0.05), and the indicators at 3 months significantly improved than that at 1 month ( P<0.05). According to the modified MacNab evaluation criteria, the effectiveness at 3 months after operation was rated as excellent in 52 cases, good in 21 cases, and poor in 13 cases, with an excellent and good rate of 84.9%. No lumbar instability was detected on flexion-extension X-ray films during follow-up. The Lee's grading of lateral lumbar stenosis at 2 days after operation showed significant improvement compared to preoperative grading ( P<0.05). CONCLUSION For lateral lumbar spinal stenosis, UBE-assisted decompression of the spinal canal requires the selection of interlaminar approach, interlaminar approach with auxiliary third incision, contralateral inclinatory approach, and paraspinal approach based on preoperative imaging findings and clinical symptoms to achieve better effectiveness.
Humans ; Spinal Stenosis/diagnostic imaging* ; Female ; Male ; Middle Aged ; Decompression, Surgical/methods* ; Aged ; Lumbar Vertebrae/surgery* ; Endoscopy/methods* ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To explore short-term clinical efficacy of minimally invasive diagnosis and treatment system for hallux valgus in guiding the treatment of hallux valgus. METHODS: From March 2021 to November 2023, 68 patients (136 feet) with hallux valgus were treated under guidance of minimally invasive diagnosis and treatment system, including 12 males and 56 females;aged from 25 to 68 years old with an average of (42.5±8.5) years old, the course of disease ranged from 3.2 to 15.6 years with an average of (10.3±2.6) years. The changes of hallux valgus angle (HVA) and intermetatarsal angle (IMA), visual analog scale (VAS) and American Orthopaedic Foot Ankle Society (AOFAS) forefoot score were recorded and compared before operation and 12 months after operation. RESULTS: Sixty-five patients (130 feet) were followed up for 12 to 15 months with an average of (13.8±0.5) months, 3 patients (6 feet) were not followed up as required. HVA and IMA improved from (35.5±3.5) ° and (12.5±2.0) ° before operation to (10.5±2.5) ° and (8.5±1.5) °12 months after operation, respectively, with statistically significant differences (P<0.05);VAS decreased from (5.5±1.2) before operation to (1.2±0.5) at 12 months after operation, and the difference was statistically significant (P<0.05);AOFAS forefoot score increased from (50.6±5.1) before operation to (93.8±5.6) at 12 months after operation, with a statistically significant difference (P<0.05). Among them, 102 feet were got excellent result, 24 feet good, and 4 feet fair. Two patients were developed calf intermuscular vein thrombosis, and were cured after 3 months of symptomatic treatment. CONCLUSION Under the guidance of minimally invasive diagnosis and treatment system for hallux valgus, the treatment of HV could obviously improve HVA and IMA, and significantly alleviate pain symptoms, and accelerate functional recovery.
Humans ; Hallux Valgus/diagnosis* ; Male ; Female ; Middle Aged ; Adult ; Aged ; Minimally Invasive Surgical Procedures/methods* ; Treatment Outcome

Individuals with congenital absence of the vas deferens (CAVD) may transmit cystic fibrosis (CF)-causing variants of the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene to their offspring through assisted reproductive technology (ART). We aimed to delineate the spectrum and estimate the prevalence of CF-causing variants in Chinese individuals with CAVD through a cohort analysis and meta-analysis. CFTR was sequenced in 145 Chinese individuals with CAVD. CFTR variants were classified as CF-causing or non-CF-causing variants regarding clinical significance. A comprehensive genotype analysis was performed in Chinese individuals with CAVD, incorporating previous studies and our study cohort. The prevalence of CF-causing variants was estimated through meta-analysis. In our cohort, 56 different CFTR variants were identified in 108 (74.5%) patients. Twenty variants were categorized as CF-causing and were detected in 28 (19.3%) patients. A comprehensive genotype analysis of 867 patients identified 174 different CFTR variants. Sixty-four were classified as CF-causing variants, 56.3% of which had not been previously reported in Chinese patients with CF. Meta-analysis showed that 14.8% (95% confidence interval [CI]: 11.0%-18.9%) CAVD cases harbored one CF-causing variant, and 68.6% (95% CI: 65.1%-72.0%) CAVD cases carried at least one CFTR variant. Our study underscores the urgent need for extensive CFTR screening, including sequencing of whole exons and flanking regions and detection of large rearrangements and deep intronic CF-causing variants, in Chinese individuals with CAVD before undergoing ART. The established CF-causing variants spectrum may aid in the development of genetic counseling strategies and preimplantation diagnosis to prevent the birth of a child with CF.
Adult ; Humans ; Male ; China ; Cohort Studies ; Cystic Fibrosis/genetics* ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; Genotype ; Male Urogenital Diseases/genetics* ; Mutation ; Vas Deferens/abnormalities* ; East Asian People/genetics*