Objective:To explore the correlation among SMAD4 gene polymorphisms, early life traumatic experience and their interactions with clinical feature of obsessive-compulsive disorder (OCD). Methods:Totally 484 OCD patients who met the DSM-Ⅳ diagnostic criteria and 368 health controls who met the enrollment criteria were recruited from September 2013 to September 2018. The Yale-Brown obsessive-compulsive scale (Y-BOCS) was used to assess the severity of obsessive-compulsive symptoms, the Beck depression inventory Ⅱ (BDI-Ⅱ) was used to assess the severity of depressive symptoms, the Beck anxiety inventory (BAI) was used to assess the severity of anxiety symptoms, and early trauma inventory-short form (ETI-SF) was used to assess early traumatic experience. SMAD4: rs12452684, rs2276163, rs17663887 and rs3819122 were genotyped using the Taqman genotyping technique. Data were analyzed using SPSS 20.0 software, and comparisons among groups were performed using chi-square test, t-test, Mann-Whitney U non-parametric test and analysis of covariance. Correlation was analyzed using Spearman correlation analysis, and interactions were analyzed using general linear model. Results:All sites except rs17663887 met the Hardy-Weinberg equilibrium (rs12452684: χ2=0.29, P=0.59; rs2276163: χ2=2.58, P=0.11; rs3819122: χ2=0.22, P=0.64).Allele, genotype frequencies of SMAD4: rs12452684, rs2276163 and rs3819122 were not statistically significant between the OCD and the health control groups ( χ2=0.02, 1.20, 0.04, all P>0.05; χ2=1.85, 3.98, 1.45, all P>0.05). The results of covariance analysis (corrected for age and gender) showed that there were significantly differences in compulsion (CC: 12.47±4.23, CT: 12.53±4.15, TT: 13.97±3.11; AA: 12.63±4.08, AC: 12.49±4.19, CC: 13.87±2.93) and total Y-BOCS scores(CC: 25.31±6.42, CT: 25.68±5.90, TT: 27.75±6.01; AA: 25.54±6.52, AC: 25.56±5.98, CC: 27.63±5.75) among the three genotypes of the SMAD4: rs2276163 and rs3819122 between the two groups ( F=3.58, 3.87, 3.48, 3.73, all P<0.05). Emotional abuse in the ETI-SF was positively correlated with obsession and total Y-BOCS scores( r=0.14, 0.14, both P<0.05). The interactions of rs2276163, rs3819122 and emotional abuse were associated with obsession scores ( F=4.65, 3.63, 2.93, all P<0.01). Conclusions:The more emotional abuse experienced in early life, the more severe obsessive-compulsive symptoms, and the interaction between the SMAD4 gene and early traumatic experience is involved in the development of OCD.

Objective To investigate the risk factors of hemodynamic instability after carotid artery stenting by meta-analysis.Methods Ten databases were searched:PubMed,ProQuest,ScienceDirect,Embase,Cochrane Library,Web of Science,China Knowledge Network,Wanfang Data,VIP Information Database,and China Biomedical Database.The search date was from inception until 2 February 2024,and meta-analysis was performed using Stata 16.0 statistical software.Results A total of 27 studies with 4199 subjects and 22 influencing factors were included.The studies showed a 37.4％(95％CI 30.3％-44.8％)incidence of haemodynamic instability after carotid stenting,Meta-analysis determined that age＞60 years(P＜0.001),hypertension(P＜0.001),calcified plaque(P＜0.001),stenosis＞70％(P=0.008),eccentric plaque(P=0.002),distance from the largest stenosis to the carotid bifurcation≤ 10 mm(P＜0.001),stenosis involvement of the balloon or bifurcation(P＜0.001),balloon post-dilation(P=0.003),open-loop stenting(P＜0.001),dilated balloon diameter≥5 mm(P=0.002),repeat balloon dilation(P=0.011)and balloon dilation pressure≥8 atm(P＜0.001)are risk factors for intraoperative and postoperative haemodynamic instability in patients undergoing carotid artery stenting surgery.Statin use was a protective factor(P＜0.001).Conclusions Medical staff working in the clinic should assess the patient's condition preoperatively,identify risk factors that may lead to haemodynamic instability,and avoid unnecessary intraoperative stimulation of patients who are already in a high-risk state.Reduce postoperative clinical complications in patients with carotid artery stenosis and improve patient recovery.

Objective:This study aimed to integrate RNA-seq data to identify key genes associated with macrophage-ferroptosis and develop a prognostic model for hepatocellular carcinoma(HCC).Methods:We retrieved a dataset from the GEO database containing transcriptome data and clinical information for 163 samples.Macrophage-related genes were identified using WGCNA and immune infiltration analyses.Ferroptosis-related genes from the FerrDbV2 database were intersected with differentially expressed genes to obtain significant macrophage-ferroptosis-related genes.Hub genes were screened via protein interaction network construction,and key genes were identified using four machine learning algorithms.These genes exhibited significant expression differences between cancer and normal tissues and were closely linked to patient prognosis.ROC curve and KM survival analyses were performed,and expression levels were validated at the transcriptome and proteome levels.Results:Four key genes RRM2,KIF20A,PCK2,and PDK4 were identified and evaluated.RRM2 and KIF20A demonstrated high importance in classification prediction models and reliable performance in ROC and KM analyses(AUC＞0.9,P＜0.05).These genes regulate cancer cell proliferation/survival and macrophage polarization/function,influencing the tumor microenvironment and HCC progression.Conclusion:RRM2 and KIF20A regulate cancer cell proliferation and survival,modulate macrophage polarization and function,and influence the immune response in the tumor microenvironment.They can serve as prognostic biomarkers and potential immunotherapy targets for hepatocellular carcinoma.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Tongue squamous cell carcinoma (TSCC) is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion. Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients. The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy. Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC. However, inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy (PTT). This study modified gold nanodots (AuNDs) with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT. The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuNDs. The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC. Moreover, owing to its stable long-term fluorescence and high X-ray attenuation coefficient, the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC, rendering it useful for early tumor detection and accurate delineation of surgical margins. In conclusion, Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.
Tongue Neoplasms/diagnostic imaging* ; Carcinoma, Squamous Cell/diagnostic imaging* ; Animals ; Gold/chemistry* ; Mice ; Photothermal Therapy/methods* ; Tomography, X-Ray Computed ; Photosensitizing Agents ; Metal Nanoparticles ; Humans ; Cell Line, Tumor

OBJECTIVE: Microcirculatory disturbance is pathologically critical to acute pancreatitis (AP), which can be effectively alleviated by traditional Chinese medicine (TCM) formulas that activate blood flow. However, there has been no evidence-based research to date. Therefore, a well-designed systematic review and meta-analysis is necessary to elucidate the therapeutic transformative benefit of improving microcirculation during AP. This study aims to confirm the therapeutic efficacy of TCM formulas and explore the potential mechanisms underlying their effects on AP treatment. METHODS: Studies from eight databases including Pubmed, Embase, Web of Science, Cochrane Library, CNKI, CBM, Wanfang, and Chinese VIP, were screened for the eligible randomized controlled trials (RCTs). The APACHE II score and effectiveness rate were set as primary outcomes, while mortality rate, complications, total hospital stays, serum amylase recovery time, the time until the disappearance of abdominal pain, microcirculation indicators, and inflammation indicators were chosen as secondary outcomes. A systematic review and meta-analysis were subsequently conducted. Network pharmacology analysis was performed to analyze potential bioactive components with relevant targets of the core herbs included in the TCM formulas for activating blood flow. RESULTS: A total of 51 RCTs (n = 3 721) were included. Compared with conventional western medical treatments alone, TCM groups were associated with lower APACHE II score (SMD =  - 1.36, 95% CI: -2.01 to - 0.71, P = 0.000) and higher effectiveness rate (RR: 1.22, 95% CI: 1.18 to 1.26, P = 0.000). Furthermore, the formulas for activating blood flow demonstrated significant efficacy in improving both microcirculation and inflammation indicators. Additionally, six core Chinese herbal medicines including Rhei Radix et Rhizoma with the highest frequency, Aurantii Fructus Immaturus, Paeoniae Radix Rubra, Bupleuri Radix, Salviae Miltiorrhizae Radix et Rhizoma, and Corydalis Rhizoma were filtered out from the adopted TCM formulas. Finally, 166 shared targets between the six herbs and AP were identified. KEGG analysis indicated that lipid and atherosclerosis pathway is highly related to microcirculation. CONCLUSION TCM formulas for activating blood flow significantly improve microcirculation and alleviate AP. Further high-quality, well-designed RCTs and deep mechanism exploration are required.

OBJECTIVE: The present study evaluated the effects of deep acupuncture at Weizhong acupoint (BL40) on bladder function and brain activity in a rat model of overactive bladder (OAB), and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture. METHODS: Adult female Sprague-Dawley rats were randomly divided into six groups, comprising a control group, model group, group treated with deep acupuncture at BL40, group treated with shallow acupuncture at BL40, group treated with acupuncture at non-acupoint next to BL40, and group treated with acupuncture at Xuanzhong (GB39). Urodynamic evaluation was used to observe the urination, and functional magnetic resonance imaging was used to observe the brain activation. The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay, and the mechanism was verified by stabilizing mast cells (MCs) or blocking tibial nerve. RESULTS: Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex (M1), periaquaductal gray matter (PAG), and pontine micturition center (PMC). It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC. Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes. Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine, substance P, and histamine in the tissues around BL40. Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats. CONCLUSION Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve, thereby regulating the activation of the brain area that controls the lower urinary tract. Please cite this article as: Liu X, Zhang CY, Du XY, Li SS, Wang YQ, Zheng Y, Deng HZ, Fang XQ, Li JY, Wang ZQ, Xu SF, Mi YQ. Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves. J Integr Med. 2025; 23(1): 46-55.
Animals ; Urinary Bladder, Overactive/physiopathology* ; Mast Cells/physiology* ; Rats, Sprague-Dawley ; Female ; Acupuncture Therapy ; Acupuncture Points ; Rats ; Brain/physiopathology* ; Tibial Nerve/physiopathology* ; Acetic Acid ; Urinary Bladder/physiopathology*

OBJECTIVE: Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control. METHODS: Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes. RESULTS: Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16. CONCLUSION A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans ; Adenoviruses, Human/isolation & purification* ; Respiratory Tract Infections/epidemiology* ; Child, Preschool ; Child ; Recombination, Genetic ; Male ; Beijing/epidemiology* ; Infant ; Female ; Phylogeny ; Adenovirus Infections, Human/epidemiology* ; Acute Disease ; Genome, Viral

Hepatocellular carcinoma （HCC） is a malignant tumor with high incidence and mortality rates worldwide. Recent studies have shown that neutrophil extracellular traps （NETs） play an important role in the development， progression， and immune escape of HCC. NETs are released by neutrophils and mainly consist of DNA， histones， and antimicrobial molecules， and in addition to immune defense， they are also involved in the initiation， metastasis， and thrombosis of HCC. This article elaborates on the formation and regulatory mechanisms of NETs， explores their potential mechanisms in the initiation， metastasis， immune escape， and thrombosis of HCC， and discusses the prospect of NETs as a target for the diagnosis and treatment of HCC， in order to provide new ideas for the precise treatment of HCC in the future and promote the early diagnosis and effective treatment of HCC.

Objective:To explore the correlation among SMAD4 gene polymorphisms, early life traumatic experience and their interactions with clinical feature of obsessive-compulsive disorder (OCD). Methods:Totally 484 OCD patients who met the DSM-Ⅳ diagnostic criteria and 368 health controls who met the enrollment criteria were recruited from September 2013 to September 2018. The Yale-Brown obsessive-compulsive scale (Y-BOCS) was used to assess the severity of obsessive-compulsive symptoms, the Beck depression inventory Ⅱ (BDI-Ⅱ) was used to assess the severity of depressive symptoms, the Beck anxiety inventory (BAI) was used to assess the severity of anxiety symptoms, and early trauma inventory-short form (ETI-SF) was used to assess early traumatic experience. SMAD4: rs12452684, rs2276163, rs17663887 and rs3819122 were genotyped using the Taqman genotyping technique. Data were analyzed using SPSS 20.0 software, and comparisons among groups were performed using chi-square test, t-test, Mann-Whitney U non-parametric test and analysis of covariance. Correlation was analyzed using Spearman correlation analysis, and interactions were analyzed using general linear model. Results:All sites except rs17663887 met the Hardy-Weinberg equilibrium (rs12452684: χ2=0.29, P=0.59; rs2276163: χ2=2.58, P=0.11; rs3819122: χ2=0.22, P=0.64).Allele, genotype frequencies of SMAD4: rs12452684, rs2276163 and rs3819122 were not statistically significant between the OCD and the health control groups ( χ2=0.02, 1.20, 0.04, all P>0.05; χ2=1.85, 3.98, 1.45, all P>0.05). The results of covariance analysis (corrected for age and gender) showed that there were significantly differences in compulsion (CC: 12.47±4.23, CT: 12.53±4.15, TT: 13.97±3.11; AA: 12.63±4.08, AC: 12.49±4.19, CC: 13.87±2.93) and total Y-BOCS scores(CC: 25.31±6.42, CT: 25.68±5.90, TT: 27.75±6.01; AA: 25.54±6.52, AC: 25.56±5.98, CC: 27.63±5.75) among the three genotypes of the SMAD4: rs2276163 and rs3819122 between the two groups ( F=3.58, 3.87, 3.48, 3.73, all P<0.05). Emotional abuse in the ETI-SF was positively correlated with obsession and total Y-BOCS scores( r=0.14, 0.14, both P<0.05). The interactions of rs2276163, rs3819122 and emotional abuse were associated with obsession scores ( F=4.65, 3.63, 2.93, all P<0.01). Conclusions:The more emotional abuse experienced in early life, the more severe obsessive-compulsive symptoms, and the interaction between the SMAD4 gene and early traumatic experience is involved in the development of OCD.