ObjectiveTo multidimensionally analyze the clinical effects of Qianyang Yuyin granules on elderly hypertensive patients through an "energy-inflammation-aging" network. MethodsRelevant datasets were retrieved from the GEO database. Gene set enrichment analysis （GSEA） was performed on the gene expression profiles of peripheral blood cells from patients with essential hypertension in dataset GSE24752. The GSEA referenced "GO gene sets" and "KEGG gene sets" to identify significantly enriched gene sets. A clinical trial was conducted using a randomized controlled study design. A total of 40 patients meeting the inclusion criteria were enrolled. The control group received standard antihypertensive treatment with angiotensin receptor blockers （ARBs） or combined calcium channel blockers （CCBs）. In contrast，the treatment group received Qianyang Yuyin Granules in addition to the standard treatment for 12 weeks. Blood pressure levels and clinical efficacy were observed，and changes in energy metabolism indicators，DNA damage markers，and senescence-associated secretory phenotype （SASP） in blood were measured using ELISA before and after treatment. ResultsGSEA results indicated significant energy metabolism dysregulation in hypertensive patients. Clinical findings showed that both groups achieved blood pressure control without significant intergroup differences. In terms of clinical efficacy，the treatment group had a significantly higher effective rate compared to the control group （95% vs 65%，P0.05）. After treatment，the treatment group showed a significant increase in NAD⁺ levels （P0.01），with higher levels compared to the control group （P0.05）. The treatment group also exhibited a greater reduction in DNA damage marker 8-OHdG （P0.01） and cell adhesion factors ICAM-1 and VCAM-1 （P0.01） compared to the control group. Pro-inflammatory cytokines IL-1β and IL-6 were significantly reduced in the treatment group （P0.01），with greater reductions compared to the control group （P0.05，P0.01）. Anti-inflammatory cytokines IFN-α，IL-4，and IL-10 were significantly elevated in the treatment group （P0.01），with higher levels compared to the control group （P0.01）. No significant adverse reactions were reported in either group. ConclusionThe "energy- inflammation- aging" network plays an important role in the pathological mechanism of hypertension patients. Qianyang Yuyin granules may delay the aging process by increasing patients' energy metabolism levels，reducing DNA oxidative damage，and maintaining the balance of inflammatory factors.

Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
Humans ; Gastrointestinal Microbiome/genetics* ; Bacteriophages/physiology* ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/methods* ; Bacteria/virology*

Objective: To observe the effect of Xipayimaizibizi oral liquid (XP) in an overactive bladder (OAB) experimental rat model and to explore its pharmacological mechanisms. Methods: Network pharmacology was used to explore the potential mechanisms of action of XP. The rats underwent bladder outlet obstruction surgery and were administered the corresponding drug concentrations by gavage for 4 weeks. The study observed the body weight, water intake, bladder and kidney indices (to evaluate their general status), urination behavior pattern (to observe frequency and urgency), and urodynamics (to measure bladder parameters). Hematoxylin and eosin and Masson's trichome staining were used to observe changes in the bladder structure. Enzyme-linked immunosorbent assay was used to measure the levels of nerve growth factor, brain-derived neurotrophic factor, and acetylcholine in the urine. The key targets involved in these mechanisms were validated using reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, and western blot in vivo/vitro experiments. Result: Network pharmacological analysis predicted that XP may alleviate OAB by affecting the cholinergic synapse and calcium signaling pathways. XP treatment significantly reduced the bladder index, improved urine behavior and urodynamic parameters, decreased the neurotransmitters in urine, and reduced the thickness of the bladder wall and collagen ratio. These results indicate that XP can alleviate OAB symptoms and improve the bladder structure. In vivo/vitro experiments further demonstrated that XP can inhibit targets, such as muscarinic acetylcholine receptor 2, and participate in cholinergic synapses to further regulate the parasympathetic nervous system. It can also reduce the overexpression of Ca2+ caused by agonists, inhibit targets such as transient receptor potential vanilloid type 1, and participate in calcium signaling pathways to maintain Ca2+ homeostasis. Conclusion These results suggest that XP inhibited bladder overactivity by maintaining Ca2+ homeostasis and regulating the parasympathetic nervous system.

Objective To systematically evaluate the efficacy and safety of three-dimensional visualization technology in assisting ablation therapy for hepatocellular carcinoma.Methods This study was conducted according to PRISMA guidelines,with a PROSPERO registration number of CRD42023488398.PubMed,Embase,Web of Science,the Cochrane Library,CNKI,Wanfang Data,VIP,and CBM were searched for Chinese and English articles on three-dimensional visualization technology in assisting ablation therapy for hepatocellular carcinoma published up to March 2023.After quality assessment and data extraction of the studies included,RevMan 5.4 software was used to perform the meta-analysis.Results A total of 11 studies were included,with 972 patients in total,among whom 447 underwent ablation assisted by three-dimensional visualization technology(3D group)and 525 underwent ablation assisted by traditional two-dimensional imaging technology(2D group).The meta-analysis showed that compared with the 2D group,the 3D group had significantly higher success rate of first-time ablation treatment(odds ratio[OR]=5.43,95%confidence interval[CI]:2.64—11.18,P<0.001),technical efficiency(OR=6.15,95%CI:3.23—11.70,P<0.001),and complete ablation rate(OR=2.50,95%CI:1.08—5.78,P=0.03),as well as significantly lower incidence rate of major complications(OR=0.45,95%CI:0.24—0.87,P=0.02),local recurrence rate(OR=0.35,95%CI:0.17—0.72,P=0.004),and local tumor progression rate(OR=0.29,95%CI:0.16—0.50,P<0.001),while there was no significant difference in the incidence rate of mild complications between the two groups(P>0.05).Conclusion Three-dimensional visualization technology is safe and feasible in assisting ablation therapy for hepatocellular carcinoma and can improve ablation rate and reduce the incidence rate of serious complications,local recurrence rate,and local tumor progression rate,thereby showing an important application value in clinical practice.

BACKGROUND:A pathophysiological feature of septic organ failure is endothelial dysfunction in sepsis(EDS).The physiological and pathological mechanism of sepsis is considered to be vascular leakage caused by endothelial dysfunction.These pathological changes lead to systemic organ injury.However,an analysis using bibliometric methods has not yet been conducted in the field of EDS.This study was conducted to provide an overview of knowledge structure and research trends in the field of EDS. METHODS:Based on previous research,a literature search was performed in the Web of Science Core Collection(WoSCC)for publications associated with EDS published between the year 2003 and 2023.Various types of data from the publications,such as citation frequency,authorship,keywords and highly cited articles,were extracted.The"Create Citation Report"feature in the WoSCC was employed to calculate the Hirsch index(h-index)and average citations per item(ACI)of authors,institutions,and countries.To conduct bibliometric and visualization analyses,three bibliometric tools were used,including R-bibliometrix,CiteSpace(co-citation analysis of references),and VOSviewer(co-authorship analysis of institutions,co-authorship analysis of authors,co-occurrence analysis of keywords). RESULTS:After excluding invalid records,the study finaly included 4,536 publications with 135,386 citations.Most of these publications originated in the USA,China,Germany,Canada,and Japan.Harvard University emerged as the most prolific institution,while professor Jong-Sup Bae and his research team at Kyungpook National University emerged as authors with the greatest influence.The"protein C","tissue factor","thrombin","glycocalyx","acute kidney injury","syndecan-1"and"biomarker"were identified as prominent areas of research.Future research may focus on molecular mechanisms(such as as vascular endothelial[VE]-cadherin regulation)and therapeutic interventions to enhance endothelial repair and function. CONCLUSION:Our findings show a growing interest in EDS research.Key areas for future research include signaling pathways,molecular mechanisms,endothelial repair,and interactions between endothelial cells and other cell types in sepsis.

Objective To investigate the effects of α7 nicotinic acetylcholine receptor(nAChR)agonist on β3-adrenoceptor agonist-induced impairment of white fat homeostasis and beige adipose formation and heat production in obese mice.Methods Forty obese C57BL/6J mice were randomized into high-fat feeding group,β3-adrenoceptor agonist-treated model group,α7 nAChR agonist group,and α7 nAChR inhibitor group(n=10),with another 10 mice with normal feeding as the blank control group.White adipose tissue from the epididymis of the mice were sampled for HE staining of the adipocytes.The expression levels of TNF-α,IL-1β,IL-10 and TGF-β in the white adipose tissue were determined by ELISA,and the mRNA levels of iNOS,Arg1,UCP-1,PRDM-16 and PGC-1α were detected using RT-qPCR.Western blotting was performed to detect the expression levels of NF-κB P65,p-JAK2,p-STAT3 in the white adipose tissue.Results Compared with those in the blank control group,the mice with high-fat feeding showed significantly increased body weight,more fat vacuoles in the white adipose tissue,increased volume of lipid droplets in the adipocytes,upregulated iNOS mRNA expression and protein expression of TNF-α and IL-1β,and lowered expression of Arg-1 mRNA and IL-10 and TGF-β proteins(P<0.01).Treatment with α7 nAChR significantly reduced mRNA levels of PRDM-16,PGC-1α and UCP-1,lowered TNF-α and IL-1β expressions,increased IL-10 and TGF-β expressions,and reduced M1/M2 macrophage ratio in the white adipose tissues(P<0.05 or 0.01).Conclusion Activation of α7 nAchR improves white adipose tissue homeostasis impairment induced by β3 agonist,promotes transformation of M1 to M2 macrophages,reduces inflammatory response in white adipose tissue,and promote beige adipogenesis and thermogenesis in obese mice.

Objective To investigate the effects of α7 nicotinic acetylcholine receptor(nAChR)agonist on β3-adrenoceptor agonist-induced impairment of white fat homeostasis and beige adipose formation and heat production in obese mice.Methods Forty obese C57BL/6J mice were randomized into high-fat feeding group,β3-adrenoceptor agonist-treated model group,α7 nAChR agonist group,and α7 nAChR inhibitor group(n=10),with another 10 mice with normal feeding as the blank control group.White adipose tissue from the epididymis of the mice were sampled for HE staining of the adipocytes.The expression levels of TNF-α,IL-1β,IL-10 and TGF-β in the white adipose tissue were determined by ELISA,and the mRNA levels of iNOS,Arg1,UCP-1,PRDM-16 and PGC-1α were detected using RT-qPCR.Western blotting was performed to detect the expression levels of NF-κB P65,p-JAK2,p-STAT3 in the white adipose tissue.Results Compared with those in the blank control group,the mice with high-fat feeding showed significantly increased body weight,more fat vacuoles in the white adipose tissue,increased volume of lipid droplets in the adipocytes,upregulated iNOS mRNA expression and protein expression of TNF-α and IL-1β,and lowered expression of Arg-1 mRNA and IL-10 and TGF-β proteins(P<0.01).Treatment with α7 nAChR significantly reduced mRNA levels of PRDM-16,PGC-1α and UCP-1,lowered TNF-α and IL-1β expressions,increased IL-10 and TGF-β expressions,and reduced M1/M2 macrophage ratio in the white adipose tissues(P<0.05 or 0.01).Conclusion Activation of α7 nAchR improves white adipose tissue homeostasis impairment induced by β3 agonist,promotes transformation of M1 to M2 macrophages,reduces inflammatory response in white adipose tissue,and promote beige adipogenesis and thermogenesis in obese mice.

Hypertensive heart disease is a common target organ damage in hypertension,resulting from the prolonged imbalance of yin and yang,as well as stasis accumulation internally.It shares common mechanism with the imbalance of cardiac homeostasis.This article combined modern medicine with traditional medicine in understanding hypertensive heart disease.It proposed that nourishing yin to subdue excessive yang and harmonizing qi and blood are the primary approaches,advocating treatment for hypertensive heart disease from deficiencies and stasis.

Fibrous dysplasia of bone (FD) is a tumorlike disease characterized by intramedullary fibrosis, in which the development of the bone in the lesion area stops at the stage of immature braided bone, with the inability to form a normal bone trabecula, resulting in structural changes and reduced mechanical strength of the bone. Repeated pathological fractures often occur with weight bearing, followed by curvature of the affected bone, limb shortening, and abnormal gait. The proximal femur is often involved in FD limb malformations, with complex types and degrees, most of which are manifested as gradually aggravating hip varus and diaphysial curvature. The proximal femur is a common site of limb deformity caused by FD, the types and severity of malformations are complex and varied, which is usually manifested as gradually aggravated varus hip joint and diaphysis bending deformity. The purpose of deformity correction is to restore the normal mechanical axis and length of the femur, thereby restoring the function of the limb, avoiding the progression of deformity and relieving the pain symptoms caused by repeated pathological microfractures, which is more important than the treatment of the lesion itself. The preoperative treatment plan should be made individually for each patient according to the location and extent of the lesion and the type of the lesion. The patients need to be followed up for a long time to adjust the correction plan. Whether the lesion should be curette and bone graft and the type of bone graft material used are still controversial. The femoral deformity of FD should be analyzed based on the principles of deformity correction, the type of deformity and the location of the apex of the deformity should be determined, the osteotomy plan should be designed, and the preoperative simulation should be performed. Both intramedullary and extramedullary fixation after osteotomy can provide sufficient biological stability. The choice of fixation device should be determined according to the specific situation during the operation. There is no obvious abnormality in bone healing and regeneration in FD patients, but dysplastic bone tissue is included in the callus formation. The limb deformity of FD patients is prone to relapse after treatment, long-term close follow-up is needed to adjust the correction plan.

Objective:To investigate the correlation between subjective hearing impairment and cognitive function in the elderly in the community of Changzhou City.Methods:This study was a retrospective cohort study. A total of 1 132 elderly people recruited from 4 communities in Changzhou City from August to October in 2023 were selected as the research objects. The social demographic and cognitive function were collected, cognitive function was assessed using the mini-mental state examination (MMSE), while the connected test, replica cube, and clock draw in the Montreal cognitive assessment (MoCA) were selected to assess visuospatial and executive function. The subjects were divided into the no-hearing impairment group (726 subjects) and hearing impairment group (406 subjects) according to the self-reported hearing impairment of the elderly. The basic data of the two groups and the differences in different cognitive domains were analyzed, and the correlation between subjective hearing impairment and cognitive function of the elderly in the community was analyzed by univariate and multivariate logistic regression analysis.Results:The incidence of cognitive impairment in the hearing impairment group was significantly higher than that in the no-hearing impairment group (20.2% vs 6.6%), the scores of location orientation, memory, attention and calculation, recall, language ability, clock draw, and the total score of MMSE, visuospatial and executive function in the hearing impairment group were all significantly lower than those in the normal hearing group [(4.76±0.78) vs (4.91±0.45) points, (2.79±0.59) vs (2.90±0.36) points, 4 (3, 5) vs 5 (4, 5) points, 2 (1, 3) vs 2 (2, 3) points, 8 (7, 9) vs 9 (8, 9) points, 2 (2, 3) vs 3 (2, 3) points, 27 (24, 29) vs 27 (26, 29) points, 3 (2, 3) vs 3 (2, 4) points] (all P<0.05). There was a positive correlation between subjective hearing impairment and cognitive function impairment in community-dwelling elderly ( OR=3.544, 95% CI: 2.410-5.213) ( P<0.001). Conclusion:The incidence of cognitive impairment is higher in the community-dwelling elderly with subjective hearing impairment, and hearing impairment is a positive correlation factor of cognitive impairment.