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1.
J Robot Surg ; 18(1): 362, 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39370475

ABSTRACT

A nephroureterectomy conventionally consists of two independent section, which will considerably prolong the operation time. We developed a novel surgical technique for robotic-assisted laparoscopic nephroureterectomy without re-docking in a single position and aimed to access the safety, feasibility, and efficiency of our novel surgical technique. From August 2021 to October 2023, 53 patients who received robotic-assisted laparoscopic nephroureterectomy were retrospectively enrolled in this study. 25 patients underwent traditional nephroureterectomy and 28 patients underwent single-position nephroureterectomy. The basic characteristics of the enroll patients, perioperative parameters, and oncological outcomes were gathered and compared between novel technique robotic surgery group and traditional surgery group. The basic characteristics between two groups had no significantly difference except for the proportion of anticoagulation therapy. The operation time in novel technique robotic surgery group was shorter than that in traditional robotic surgery group, although there was no significant difference (p = 0.403). Lymph-node dissection in novel technique robotic surgery group was obvious more common than that in traditional robotic surgery group (p = 0.037), while the incision length in novel technique robotic surgery group was obviously shorter than that in traditional robotic surgery group (p < 0.001). The oncological outcomes showed no difference between two groups. Compared with traditional robotic-assisted laparoscopic nephroureterectomy, the innovative surgical technique of robotic-assisted laparoscopic nephroureterectomy in a single position showed the advantages of less surgical time, streamlined lymph-node dissection, less trauma, and expedited postoperative recovery, which is worth promoting in clinical practice.


Subject(s)
Laparoscopy , Nephroureterectomy , Operative Time , Robotic Surgical Procedures , Humans , Robotic Surgical Procedures/methods , Nephroureterectomy/methods , Laparoscopy/methods , Female , Male , Middle Aged , Retrospective Studies , Aged , Treatment Outcome , Lymph Node Excision/methods , Kidney Neoplasms/surgery , Feasibility Studies
2.
Nat Commun ; 15(1): 8479, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39353909

ABSTRACT

The majority of viruses classified as pandemic threats are enveloped viruses which enter the cell through receptor-mediated endocytosis and take advantage of endosomal acidification to activate their fusion machinery. Here we report that the endosomal fusion of low pH-requiring viruses is highly dependent on TRPM7, a widely expressed TRP channel that is located on the plasma membrane and in intracellular vesicles. Using several viral infection systems expressing the envelope glycoproteins of various viruses, we find that loss of TRPM7 protects cells from infection by Lassa, LCMV, Ebola, Influenza, MERS, SARS-CoV-1, and SARS-CoV-2. TRPM7 ion channel activity is intrinsically necessary to acidify virus-laden endosomes but is expendable for several other endosomal acidification pathways. We propose a model wherein TRPM7 ion channel activity provides a countercurrent of cations from endosomal lumen to cytosol necessary to sustain the pumping of protons into these virus-laden endosomes. This study demonstrates the possibility of developing a broad-spectrum, TRPM7-targeting antiviral drug to subvert the endosomal fusion of low pH-dependent enveloped viruses.


Subject(s)
Endosomes , TRPM Cation Channels , Virus Internalization , TRPM Cation Channels/metabolism , TRPM Cation Channels/genetics , Endosomes/metabolism , Endosomes/virology , Hydrogen-Ion Concentration , Humans , Animals , HEK293 Cells , SARS-CoV-2/physiology , SARS-CoV-2/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Ebolavirus/physiology , Ebolavirus/metabolism , Lymphocytic choriomeningitis virus/physiology , Chlorocebus aethiops , Viral Envelope/metabolism , Lassa virus/metabolism , Lassa virus/physiology
3.
J Sci Food Agric ; 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39264139

ABSTRACT

BACKGROUND: Ginseng-Douchi (GD) is a complex fermented product of ginseng and soybean, similar to natto, and is effective in the treatment of hyperlipidemia, but the mechanism of action involved needs to be further explored. RESULTS: The present study combines a comprehensive strategy of network pharmacology and metabolomics to explore the lipid-lowering mechanism of GD. First, a hyperlipidemia rats model induced by a high-fat diet was established to evaluate the therapeutic effects of GD. Second, potential biomarkers were identified using serum metabolomics and metabolic pathway analysis was performed with MetaboAnalyst. Third, network pharmacology is used to find potential therapeutic targets based on the blood-influencing components of GD. Finally, core targets were obtained through a target-metabolite and the enrichment analysis of biomarkers-genes. Biochemistry analysis showed that GD exerted hypolipidemic effects on hyperlipidemic rats. Nineteen potential biomarkers for the GD treatment of hyperlipidemia were identified by metabolomics, which was mainly involved in linoleic acid metabolism, glycerophospholipid metabolism, ether lipid metabolism, alpha-linolenic acid metabolism and glycosylphosphatidylinositol-anchor biosynthesis. GD had a callback function for ether lipid metabolism and glycerophospholipid metabolism pathways. Eighteen blood components were identified in serum, associated with 85 potential therapeutic targets. The joint analysis showed that three core therapeutic targets were regulated by GD, including PIK3CA, AKT1 and EGFR. CONCLUSION: This study combines serum medicinal chemistry of traditional Chinese medicine, network pharmacology and metabolomics to reveal the regulatory mechanism of GD on hyperlipidemia. © 2024 Society of Chemical Industry.

4.
Cell Signal ; 124: 111400, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39277093

ABSTRACT

OBJECTIVE: This study investigated whether Mulberryside A (MBA) can attenuate cigarette smoke extract (CSE)-induced autophagy through a Sirt1-dependent pathway, thereby attenuating atherosclerosis in ApoE-/- mice. METHODS: After treating human umbilical vein endothelial cells (HUVECs) with CSE and MBA, an MTT assay was performed to detect cell activity. Immunofluorescence and Western blotting were used to determine the expressions of autophagy-related proteins, Sirt1 and HIF-1α. Lentivirus and siRNA were used to construct overexpression and silencing (Sirt1 and HIF-1α) models. The in vivo inflammatory effects of CS on atherosclerosis in ApoE-/- mice were assessed by exposing mice to CS and MBA treatment. HE staining was used to detect atherosclerosis in mouse aortic tissue, and electron microscopy was used to detect autophagy of endothelial cells. RESULTS: CSE promoted autophagy in HUVECs, down-regulated Sirt1, and up-regulated HIF-1α expression. MBA treatment, overexpression of Sirt1, or silencing of HIF-1α attenuated CSE-induced autophagy, while MBA reversed CSE-induced downregulation of Sirt1 and upregulation of HIF-1α. However, overexpression of HIF-1α increased autophagy in HUVECs and attenuated the protective effect of Sirt1 overexpression or MBA on CSE-induced autophagy in HUVECs. In vivo experiments also demonstrated that MBA attenuates CS-induced aortic autophagy in ApoE-/- mice and up-regulates Sirt1 and downregulates HIF-1α expression. CONCLUSIONS: MBA attenuates CSE-induced autophagy through the Sirt1-HIF-1α axis, thereby attenuating atherosclerosis in ApoE-/- mice.

5.
Wei Sheng Yan Jiu ; 53(5): 820-827, 2024 Sep.
Article in Chinese | MEDLINE | ID: mdl-39308115

ABSTRACT

OBJECTIVE: To estimate the prevalence of falls and examine the association between the dietary diversity and falls among older Chinese adults. METHODS: We used data from the 2018 Chinese Longitudinal Healthy Longevity Survey(CLHLS), a nationwide survey with 10 698 adults aged ≥65 years old in 23 provinces of China. Dietary diversity score(DDS) was constructed based on 11 items of a food frequency questionnaire. Participants were assigned into 4 groups(Q1, Q2, Q3 and Q4) according to the quartile of DDS. The outcome observed was the incidence of fall in the past year acquired by questionnaire. Multinomial logistic regression was used to examine the association between DDS and the risk of falls in the elderly. RESULTS: Among the 10 698 participants, 4686(43.8%) were male, and 6012(56.2%) were female, with a mean(SD) age of 85.03(11.8).6191(57.9%) of them were came from urban. Fall was reported by 22.9% of the 10698 participants. After adjustment for age, sex, ethnicity, educational background, marital status, residence, sufficient income, smoking, drinking, regular exercise, sleep duration, Precentral obesity and central obesity, vision impairment, disability, nervous system diseases, and arthritis diseases, compared to the Q1 of DDS, OR were 0.83(95% CI 0.74-0.94) for Q2, 0.85(95% CI 0.74-0.97) for Q3, and 0.76(95% CI 0.66-0.81) for Q4(P_(trend)<0.01). In addition, a significant association was observed between higher consumption of fresh vegetables, fresh fruits and beans, with lower risk of falls, OR were 0.76(95% CI 0.66-0.87), 0.81(95% CI 0.73-0.89) and 0.88(95% CI 0.80-0.96), respectively. CONCLUSION: A higher DDS was associated with a lower risk of falls in the Chinese aged 65 years and above.


Subject(s)
Accidental Falls , Diet , Aged , Aged, 80 and over , Female , Humans , Male , Accidental Falls/statistics & numerical data , China/epidemiology , Diet/statistics & numerical data , East Asian People , Longitudinal Studies , Prevalence , Risk Factors , Surveys and Questionnaires
6.
Front Mol Neurosci ; 17: 1400118, 2024.
Article in English | MEDLINE | ID: mdl-39315294

ABSTRACT

The transient receptor potential vanilloid 1 (TRPV1) channel plays a dual role in peripheral neuropathic pain (NeuP) by acting as a "pain switch" through its sensitization and desensitization. Hyperalgesia, commonly resulting from tissue injury or inflammation, involves the sensitization of TRPV1 channels, which modulates sensory transmission from primary afferent nociceptors to spinal dorsal horn neurons. In chemotherapy-induced peripheral neuropathy (CIPN), TRPV1 is implicated in neuropathic pain mechanisms due to its interaction with ion channels, neurotransmitter signaling, and oxidative stress. Sensitization of TRPV1 in dorsal root ganglion neurons contributes to CIPN development, and inhibition of TRPV1 channels can reduce chemotherapy-induced mechanical hypersensitivity. In diabetic peripheral neuropathy (DPN), TRPV1 is involved in pain modulation through pathways including reactive oxygen species and cytokine production. TRPV1's interaction with TRPA1 channels further influences chronic pain onset and progression. Therapeutically, capsaicin, a TRPV1 agonist, can induce analgesia through receptor desensitization, while TRPV1 antagonists and siRNA targeting TRPV1 show promise in preclinical studies. Cannabinoid modulation of TRPV1 provides another potential pathway for alleviating neuropathic pain. This review summarizes recent preclinical research on TRPV1 in association with peripheral NeuP.

7.
Folia Biol (Praha) ; 70(2): 104-112, 2024.
Article in English | MEDLINE | ID: mdl-39231318

ABSTRACT

Circular RNAs (circRNAs) have played an essential role in cancer development. This study aimed to illustrate the impact and potential mechanism of circRACGAP1 action in NSCLC development. The expression patterns of circRACGAP1, miR-1296, and CDK2 in NSCLC tissues and cell lines were analysed by RT-qPCR. The function of circRACGAP1 in NSCLC cell proliferation and apoptosis was investigated using the CCK-8 assay, flow cytometry, TUNEL staining, and Western blot. The interaction among circRACGAP1, miR-1296, and CDK2 was clarified by dual-luciferase reporter assay while the correlation was confirmed by the Pearson correlation coefficient. The expression of circRACGAP1 and CDK2 was up-regulated in NSCLC tissues, while the expression of miR-1296 was down-regulated. Cell function studies further revealed that circRACGAP1 could promote NSCLC cell proliferation, accelerate the cell cycle process, up-regulate B-cell lymphoma 2 (Bcl2) expression, and down-regulate Bcl2-associated X (Bax) expression. miR-1296 was identified as a downstream target to reverse circRACGAP1-mediated cell proliferation. miR-1296 directly targeted the 3'-UTR of CDK2 to regulate proliferation and apoptosis of NSCLC cells. Additionally, the dual-luciferase reporter assay and Pearson correlation coefficient analysis proved that circRACGAP1 acted in NSCLC cells by negatively regulating miR-1296 expression and positively regulating CDK2 expression. In summary, our study revealed that circRACGAP1 promoted NSCLC cell proliferation by regulating the miR-1296/CDK2 pathway, providing potential diagnostic and therapeutic targets for NSCLC.


Subject(s)
Apoptosis , Carcinoma, Non-Small-Cell Lung , Cell Proliferation , Cyclin-Dependent Kinase 2 , Lung Neoplasms , MicroRNAs , RNA, Circular , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Cell Proliferation/genetics , Cyclin-Dependent Kinase 2/metabolism , Cyclin-Dependent Kinase 2/genetics , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Cell Line, Tumor , RNA, Circular/genetics , RNA, Circular/metabolism , Apoptosis/genetics , Gene Expression Regulation, Neoplastic , Signal Transduction/genetics , GTPase-Activating Proteins/genetics , GTPase-Activating Proteins/metabolism
8.
J Ethnopharmacol ; 337(Pt 1): 118829, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39278295

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Platycodonis radix (PR), the root of Platycodon grandiflorus (Jacq.) A. DC., is a traditional Chinese medicine recognized for its dual role as both a medicinal and dietary substance, exhibiting significant anti-inflammatory properties. It is frequently utilized in the treatment of lung diseases. However, the molecular mechanisms by which PR exerts its effects in the treatment of acute lung injury (ALI) remain unclear. AIM OF THE STUDY: This study presents a novel strategy that integrates network pharmacology, molecular docking, untargeted metabolomics analysis and experimental validation to investigate the molecular mechanisms through which PR treats ALI. MATERIALS AND METHOD: Initially, the bioactive components of PR, along with its targets and pathways in the treatment of ALI, were identified using network pharmacology. Following this, preliminary validation was conducted through molecular docking. The active ingredients in the aqueous extract of PR were characterized using HPLC-MS. Finally, in vivo and in vitro experiments were performed to further validate the findings from the network pharmacology. RESULTS: A total of 14 bioactive components and 156 effective targets were identified using the TCMSP, DisGeNET, Genecard, OMIM databases and Venny 2.1.0. Protein-protein interaction (PPI) analysis revealed 22 core targets including TP53, AKT1, STAT3 and JUN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these targets primarily participate in the regulation of cellular apoptosis, lung cancer and inflammatory pathways. Molecular docking demonstrated that four bioactive components exhibited strong affinities with their respective docking targets. LC-MS analysis confirmed that the aqueous extract of PR contained 87 components, including two active ingredients identified through network pharmacology and molecular docking. Preliminary validation was conducted in mice with ALI induced by acute PM2.5 exposure, revealing that the aqueous extract of PR reduced inflammatory factor levels in bronchoalveolar lavage fluid, enhanced antioxidant capacity in lung tissue, and decreased lung cell apoptosis in PM2.5-exposed mice. Notably, PR alleviated PM2.5-induced ALI through the STAT3, JUN, and AKT1 signaling pathways. Similarly, the results of in vitro intervention experiments further confirmed that the aqueous extract of PR protected pulmonary epithelial cells against PM2.5 exposure through activating AKT1 sinalling pathway, and inhibiting STAT3 and JUN signalling pathways. CONCLUSION: This study identifies the active components of PR and elucidates the molecular mechanisms by which PR alleviates ALI, specifically by inhibiting the phosphorylation levels of STAT3 and c-JUN, or by activating the phosphorylation level of AKT1. These results provide a foundational basis for the application of PR in the treatment or prevention of lung injuries induced by particulate matter.

9.
Nephrology (Carlton) ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39229715

ABSTRACT

AIM: Inflammation plays a critical role in the progression of diabetic nephropathy. Peroxisome proliferator-activated receptor gamma (PPARγ) and its coactivator PPARγ coactivator-1 alpha (PGC-1α) enhance mitochondrial biogenesis and cellular energy metabolism but inhibit inflammation. However, the molecular mechanism through which these two proteins cooperate in the kidney remains unclear. The aim of the present study was to investigate this mechanism. METHODS: HK-2 human proximal tubular cells were stimulated by inflammatory factors, the expression of PPARγ and PGC-1α were determined via reverse transcription-quantitative polymerase chain reaction (PCR) and western blotting (WB), and DNA binding capacity was measured by an EMSA. Furthermore, db/db mice were used to establish a diabetic nephropathy model and were administered PPARγ and PGC-1α activators. Kidney injury was evaluated microscopically, and the inflammatory response was assessed via WB, immunohistochemistry and immunofluorescence staining. Besides, HK-2 cells were stimulated by high glucose and inflammatory factors with and without ZLN005 treatment, the expression of PPARγ, PGC-1α, p-p65 and p65 were determined via qPCR and WB. RESULTS: Our results revealed that both TNF-α and IL-1ß significantly decreased PPARγ and PGC-1 expression in vitro. Cytokines obviously decreased PPARγ DNA binding capacity. Moreover, we detected rapid activation of the NF-κB pathway in the presence of TNF-α or IL-1ß. PPARγ and PGC-1α activators effectively protected against diabetic nephropathy and suppressed NF-κB expression both in db/db mice and HK-2 cells. CONCLUSION: PPARγ and its coactivator PGC-1α actively participate in protecting against renal inflammation by regulating the NF-κB pathway, which highlights their potential as therapeutic targets for renal diseases.

10.
J Orthop Translat ; 48: 163-175, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39257437

ABSTRACT

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: "Graft Selection" and "Clinical Outcome Evaluation" during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive "gold standard" graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

11.
Contemp Clin Trials Commun ; 41: 101355, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39280785

ABSTRACT

Background: Plantar fasciitis (PF) is one of the most common causes of plantar heel pain, and previous studies found that acupuncture is effective for relieving pain in patients with PF. Nevertheless, the impact of different sessions of electroacupuncture on PF has not been investigated through randomized, controlled trials. Methods/design: This is a two parallel-group, assessor-blinded, randomized controlled trial, consisting of a four-week treatment phase followed by a 12-week follow-up. Eighty patients with chronic PF will be recruited and randomly allocated to receive 12 (three sessions per week; the multiple electroacupuncture weekly treatment group (group M)) or four (one session per week; single electroacupuncture weekly treatment group (group S)) sessions of electroacupuncture treatment in a 1:1 ratio. The primary outcome to be studied is the response rate, defined as a minimum of 50 % improvement in most severe pain intensity with first steps in the morning, compared with baseline. We will perform all analyses based on the intention-to-treat principle, with differences considered significant when the P value < 0.05 on a two-sided basis. Discussion: This prospective trial will provide high-quality evidence on evaluating the efficacy and safety of different electroacupuncture sessions (one session per week versus three sessions per week) for chronic PF. This study aims to contribute in produce up-to-date, rigorous evidence on the most effective frequency of electroacupuncture in managing chronic PF.Trial registration Clinicaltrials.gov Identifier: NCT06284993. Registered on February 17, 2024.

12.
Nanomedicine (Lond) ; 19(23): 1867-1878, 2024.
Article in English | MEDLINE | ID: mdl-39109508

ABSTRACT

Aim: We synthesized MgO NPs via sol-gel reaction and investigated them as carriers to deliver Mg2+ to the affected joint for osteoarthritis (OA).Materials & methods: The physicochemical properties of samples were characterized by transmission electron microscope (TEM), dynamic light scattering (DLS) and x-ray diffraction (XRD). The release of Mg2+ was monitored by ICP-MS. The potential cytotoxicity was evaluated using MTT assay. The efficacy and biosafety were evaluated in a rabbit OA model.Results: MgO NPs can prolong the Mg2+ release time from 0.5 h to 12 h. No significant cytotoxicity was observed when concentrations below 250 µg/ml. Intra-articular samples could effectively alleviate the degeneration and destruction of the cartilage.Conclusion: this study demonstrates the potential of MgO NPs as a safe and effective treatment of OA. Simultaneously, the size of the particles may play a significant role in influencing the therapeutic outcome.


[Box: see text].


Subject(s)
Magnesium Oxide , Osteoarthritis , Animals , Rabbits , Magnesium Oxide/chemistry , Osteoarthritis/drug therapy , Osteoarthritis/pathology , Particle Size , Nanoparticles/chemistry , Humans , Cell Survival/drug effects , Phase Transition , Magnesium/chemistry , Chondrocytes/drug effects , Drug Carriers/chemistry , Drug Liberation , Disease Models, Animal
13.
JAMA ; 332(13): 1103-1104, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39172478

ABSTRACT

A patient had multiple erythematous macules and patches on the trunk, hyperpigmented patches on the intergluteal cleft and subgluteal fold, and poikiloderma in the axillae; results of laboratory testing, including antinuclear antibody test, were unremarkable. What is the diagnosis and what would you do next?


Subject(s)
Mycosis Fungoides , PUVA Therapy , Skin Neoplasms , Humans , Male , Middle Aged , Diagnosis, Differential , Skin Neoplasms/blood , Skin Neoplasms/diagnosis , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Mycosis Fungoides/blood , Mycosis Fungoides/diagnosis , Mycosis Fungoides/drug therapy , Mycosis Fungoides/pathology , Axilla , Skin , Biopsy , Positron-Emission Tomography , Lymph Nodes/diagnostic imaging , Treatment Outcome
14.
Clin Kidney J ; 17(8): sfae209, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39145144

ABSTRACT

Background: This study investigates the link between genetic variants associated with kidney function and immunoglobulin A (IgA) nephropathy (IgAN) progression. Methods: We recruited 961 biopsy-proven IgAN patients and 651 non-IgAN end-stage renal disease (ESRD) patients from Ruijin Hospital. Clinical and renal pathological data were collected. The primary outcome was the time to ESRD. A healthy population was defined as estimated glomerular filtration rate >60 mL/min/1.73 m2 without albuminuria or hematuria. Fifteen single-nucleotide polymorphisms (SNPs) were selected from a genome-wide association study of kidney function and genotyped by the SNaPshot. Immunohistochemistry in renal tissue and ELISA in urine samples were performed to explore the potential functions of genetic variations. Results: The rs77924615-G was independently associated with an increased risk for ESRD in IgAN patients after adjustments for clinical and pathologic indices, and treatment (adjusted hazard ratio 2.10; 95% confidence interval 1.14-3.88). No significant differences in ESRD-free survival time were found among different genotypes in non-IgAN ESRD patients (log-rank, P = .480). Moreover, rs77924615 exhibited allele-specific enhancer activity by dual-luciferase reporter assay. Accordingly, the urinary uromodulin-creatinine ratio (uUCR) was significantly higher in healthy individuals with rs77924615 AG or GG than in individuals with AA. Furthermore, uromodulin expression in tubular epithelial cells was higher in patients with rs77924615 AG or GG. Finally, we confirmed that an increased uUCR (P = .009) was associated with faster IgAN progression. Conclusion: The SNP rs77924615, which modulates the enhancer activity of the UMOD gene, is associated with renal function deterioration in IgAN patients by increasing uromodulin levels in both the renal tubular epithelium and urine.

15.
Article in English | MEDLINE | ID: mdl-39207845

ABSTRACT

INTRODUCTION: This study compared the effectiveness and safety profiles of obinutuzumab and rituximab in the treatment of patients with primary membranous nephropathy. METHODS: Patients with primary membranous nephropathy who had urine protein ≥ 3.5 g/24 hours and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 despite six months of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker and treatment with obinutuzumab or rituximab were included and matched by propensity score (ratio: 1:2) based on age, sex, urine protein, eGFR, and titers of Anti-Phospholipase A2 receptor (PLA2R) antibody. The primary outcome was defined as a combination of partial or complete remission at 12 months. Logistic regression models, Kaplan Meier curves, and absolute risk differences were employed to compare the therapeutic effectiveness and safety profiles of obinutuzumab and rituximab. RESULTS: Sixty-three patients with primary membranous nephropathy were included in the study, with 21 patients receiving obinutuzumab and 42 patients receiving rituximab. At 12 months, the primary outcome was achieved in 20 of 21 patients in the obinutuzumab group and 28 of 42 patients in the rituximab group (obinutuzumab vs. rituximab: 95% vs. 67%; odds ratio (OR): 10.00, 95% confidence intervals (CI):1.21-82.35, P=0.03). Moreover, patients in the obinutuzumab group acquired more complete remission (obinutuzumab vs. rituximab: 38% vs. 14%; OR: 3.69, 95% CI:1.08-12.68, P=0.04). In PLA2R-associated primary membranous nephropathy subgroup analyses, patients in obinutuzumab group sustained lower CD19 B cell counts (CD19 B cell counts: median (IQR) 0 (0-6) cells/ul vs. 20 (3-58) cells/ul, P=0.002) and were more prone to achieve immunological remission (defined as PLA2R antibody <2 RU/ml) at six months [obinutuzumab vs. rituximab: 92% (12 out of 13) vs. 64% (16 out of 25), P=0.06] than rituximab. Both treatment regimens were well tolerated. CONCLUSIONS: Our study demonstrated that obinutuzumab is associated with higher odds of clinical remission compared to rituximab at 12 months which may be due to higher immunological remission at six months with a similar safety profile in patients with primary membranous nephropathy.

16.
Infect Dis Model ; 9(4): 1138-1146, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39022297

ABSTRACT

Plant epidemics are often associated with weather-related variables. It is difficult to identify weather-related predictors for models predicting plant epidemics. In the article by Shah et al., to predict Fusarium head blight (FHB) epidemics of wheat, they explored a functional approach using scalar-on-function regression to model a binary outcome (FHB epidemic or non-epidemic) with respect to weather time series spanning 140 days relative to anthesis. The scalar-on-function models fit the data better than previously described logistic regression models. In this work, given the same dataset and models, we attempt to reproduce the article by Shah et al. using a different approach, boosted regression trees. After fitting, the classification accuracy and model statistics are surprisingly good.

17.
Sensors (Basel) ; 24(13)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39001058

ABSTRACT

Compelling evidence has shown that geomagnetic disturbances in vertical intensity polarization before great earthquakes are promising precursors across diverse rupture conditions. However, the geomagnetic vertical intensity polarization method uses the spectrum of smooth signals, and the anomalous waveforms of seismic electromagnetic radiation, which are basically nonstationary, have not been adequately considered. By combining pulse amplitude analysis and an experimental study of the cumulative frequency of anomalies, we found that the pulse amplitudes before the 2022 Luding M6.8 earthquake show characteristics of multiple synchronous anomalies, with the highest (or higher) values occurring during the analyzed period. Similar synchronous anomalies were observed before the 2021 Yangbi M6.4 earthquake, the 2022 Lushan M6.1 earthquake and the 2022 Malcolm M6.0 earthquake, and these anomalies indicate migration from the periphery toward the epicenters over time. The synchronous changes are in line with the recognition of previous geomagnetic anomalies with characteristics of high values before an earthquake and gradual recovery after the earthquake. Our study suggests that the pulse amplitude is effective for extracting anomalies in geomagnetic vertical intensity polarization, especially in the presence of nonstationary signals when utilizing observations from multiple station arrays. Our findings highlight the importance of incorporating pulse amplitude analysis into earthquake prediction research on geomagnetic disturbances.

18.
Chin Herb Med ; 16(3): 392-400, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39072194

ABSTRACT

In Northeast China, Goubao pickle is a popular food fermented from the roots of Platycodon grandiflorum as the main material, offering a unique flavor and rich nutritional value. Platycosides in roots of P. grandiflorum may play a crucial role in determining the quality of Goubao pickle through microorganism fermentation. However, biotransfermation of platycosides has not been reviewed during fermentation. In this study, we reviewed platycosides in chemical diversity, metabolic processes in vivo, biotransformation of platycosides in vitro, and pharmacological effects. Finally, we also discussed how to improve the bioactive secondary platycosides we desire by regulating enzymes from microorganisms in the future.

19.
Food Chem ; 458: 140267, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-38968717

ABSTRACT

Recently, with changes in dietary patterns, there has been increased interest in the concept of food and medicine homology, which can help prevent disease development. This has led to a growing focus on the development of functional health foods derived from edible herbal sources. Polysaccharides, found in many edible herbal sources, are gaining popularity as natural ingredients in the production of functional food products. The gut microbiota can effectively utilize most edible herbal polysaccharides (EHPs) and produce beneficial metabolites; therefore, the prebiotic potential of EHPs is gradually being recognized. In this review, we comprehensively discuss the structural features and characterization of EHPs to promote gut microbiota regulation as well as the structure-activity relationship between EHPs and gut microbiota. As prebiotics, intestinal microbiota can use EHPs to indirectly produce metabolites such as short-chain fatty acids to promote overall health; on the other hand, different EHP structures possess some degree of selectivity on gut microbiota regulation. Moreover, we evaluate the functionality and mechanism underlying EHPs in terms of anticancer activity, antimetabolic diseases, anti-inflammatory activity, and anti-neuropsychiatric diseases.


Subject(s)
Gastrointestinal Microbiome , Polysaccharides , Prebiotics , Gastrointestinal Microbiome/drug effects , Prebiotics/analysis , Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/metabolism , Humans , Animals , Plants, Edible/chemistry , Bacteria/metabolism , Bacteria/classification , Bacteria/drug effects , Bacteria/genetics
20.
Ann Intern Med ; 177(8): 1048-1057, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38950397

ABSTRACT

BACKGROUND: Acupuncture may improve degenerative lumbar spinal stenosis (DLSS), but evidence is insufficient. OBJECTIVE: To investigate the effect of acupuncture for DLSS. DESIGN: Multicenter randomized clinical trial. (ClinicalTrials.gov: NCT03784729). SETTING: 5 hospitals in China. PARTICIPANTS: Patients with DLSS and predominantly neurogenic claudication pain symptoms. INTERVENTION: 18 sessions of acupuncture or sham acupuncture (SA) over 6 weeks, with 24-week follow-up after treatment. MEASUREMENTS: The primary outcome was change from baseline in the modified Roland-Morris Disability Questionnaire ([RMDQ] score range, 0 to 24; minimal clinically important difference [MCID], 2 to 3). Secondary outcomes were the proportion of participants achieving minimal (30% reduction from baseline) and substantial (50% reduction from baseline) clinically meaningful improvement per the modified RMDQ. RESULTS: A total of 196 participants (98 in each group) were enrolled. The mean modified RMDQ score was 12.6 (95% CI, 11.8 to 13.4) in the acupuncture group and 12.7 (CI, 12.0 to 13.3) in the SA group at baseline, and decreased to 8.1 (CI, 7.1 to 9.1) and 9.5 (CI, 8.6 to 10.4) at 6 weeks, with an adjusted difference in mean change of -1.3 (CI, -2.6 to -0.03; P = 0.044), indicating a 43.3% greater improvement compared with SA. The between-group difference in the proportion of participants achieving minimal and substantial clinically meaningful improvement was 16.0% (CI, 1.6% to 30.4%) and 12.6% (CI, -1.0% to 26.2%) at 6 weeks. Three cases of treatment-related adverse events were reported in the acupuncture group, and 3 were reported in the SA group. All events were mild and transient. LIMITATION: The SA could produce physiologic effects. CONCLUSION: Acupuncture may relieve pain-specific disability among patients with DLSS and predominantly neurogenic claudication pain symptoms, although the difference with SA did not reach MCID. The effects may last 24 weeks after 6-week treatment. PRIMARY FUNDING SOURCE: 2019 National Administration of Traditional Chinese Medicine "Project of building evidence-based practice capacity for TCM-Project BEBPC-TCM" (NO. 2019XZZX-ZJ).


Subject(s)
Acupuncture Therapy , Intermittent Claudication , Lumbar Vertebrae , Spinal Stenosis , Humans , Spinal Stenosis/complications , Spinal Stenosis/therapy , Male , Female , Middle Aged , Intermittent Claudication/therapy , Aged , Treatment Outcome , Disability Evaluation
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