As one of the chronic diseases with high incidence in contemporary society, cervical spondylosis has increasing patient groups who gradually present a low age, and it seriously affects social and public health. Although modern medicine has made great progress in the pathological research and clinical treatment of cervical spondylosis, patients still face gastrointestinal side effects of nonsteroidal anti-inflammatory drugs(NSAIDs), neck pain, limited mobility, upper limb numbness, and other symptoms after conservative or surgical treatment. In the theory of traditional Chinese medicine(TCM), cervical spondylosis belongs to the categories of "Bi syndrome" "stiff neck" "stiff Bi", etc. With the change of the times, the change of lifestyle, and the application of western medicine treatment, the etiology and pathogenesis of TCM in cervical spondylosis also show new characteristics. In terms of etiology and pathogenesis, it involves the invasion of wind, cold, and dampness, long-term strain, liver and kidney deficiency, Qi and blood stasis, which are associated with factors such as cervical degeneration, muscle tension and spasm, intervertebral disc herniation, and nerve root compression in modern medicine. In terms of the evolution of pathogenesis, in the early stage, wind, cold, and dampness, were more common in Xuanfu, resulting in unfavorable muscles and bones, poor flow of Qi and blood, and cervical spondylosis and radiculopathy. Medium-term phlegm stasis and internal knots, sluggish muscles and veins, and long-term weathering and fire are more likely to occur in the vertebral artery and sympathetic radiculopathy. In the later stage, the positive Qi is depleted; the true Yin is damaged, and the viscera Qi and blood are deficient, which is most common in cervical myelopathy. The strategy of treating cervical spondylosis with TCM classic formulas applies Gegen Decoction, Wutou Decoction, Qianghuo Shengshi Decoction, Mahuang Jiazhu Decoction to patients with wind, cold, and dampness. Patients with phlegm dampness and blood stasis are treated with Huoxue Xiaoling Dan, Jinlingzi Powder, Siwu Decoction, Banxia Baizhu Tianma Decoction, Shuanghe Decoction, etc. For those patients with liver, spleen, and kidney deficiency, Huangqi Guizhi Wuwu Decoction, Tianma Gouteng Decoction, Guishao Dihuang Pills, Shenling Baizhu Powder, and Lizhong Decoction are used to invigorate the spleen, nourish Qi and blood, and tonify liver and kidney. In clinical practice, the authors advocate a safe and effective treatment plan of classic formulas based on deficiency and excess, the integration of formulas and syndromes, and the combination of modern research results, so as to relieve symptoms, reduce recurrence, and reduce medical burden.
Humans ; Spondylosis/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Cervical Vertebrae/pathology*

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

The interest in covalent drugs has resurged in recent decades, spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening. Herein, we present CarsiDock-Cov, a new paradigm distinguishing itself as the first deep learning (DL)-guided approach for covalent docking. CarsiDock-Cov retains the core components of its non-covalent predecessor, leveraging a DL model pretrained on millions of docking complexes to predict protein-ligand distance matrices, along with a dedicated-designed geometric optimization procedure to convert these distances into refined binding poses. Additionally, it incorporates several key enhancements specifically tailored to optimize the protocol for covalent docking applications. Our approach has been extensively validated on multiple public datasets regarding the docking and screening of covalent ligands, and the results indicate that our approach not only achieves comparably improved applicability compared to its non-covalent predecessor, but also exhibits competitive performance against various state-of-the-art covalent docking tools. Collectively, our approach represents a significant advance in covalent docking methodology, offering an automated and efficient solution that shows considerable promise for accelerating covalent drug discovery and design.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective To analyze the correlation of copper death inducer ferredoxin 1(FDX1)and lipoic acid(LA)with the occurrence and severity of coronary atherosclerosis and explore their roles in coronary heart disease(CHD).Methods We analyzed the data of 226 patients undergoing coronary artery angiography(CAG)in our hospital between October,2021 and October,2022,including 47 patients with normal CAG findings(control group)and 179 patients with mild,moderate or severe coronary artery stenosis(CHD group).Serum FDX1 and LA levels were determined with ELISA for all the patients.We also examined pathological changes in the aorta of normal and ApoE-/-mice using HE staining and observed collagen fiber deposition with Sirius red staining.Immunohistochemistry was used to detect the expression and distribution of FDX1 and LA in the aorta,and RT-PCR was performed to detect the expressions of FDX1,LIAS and ACO2 mRNAs in the myocardial tissues.Results Compared with the control patients,CHD patients had significantly lower serum FDX1 and LA levels,which decreased progressively as coronary artery stenosis worsened(P<0.01)and as the number of involved coronary artery branches increased(P<0.05).Serum FDX1 and LA levels were positively correlated(r=0.451,P<0.01)and they both negatively correlated with the Gensini score(r=-0.241 and-0.273,respectively;P<0.01).Compared with normal mice,ApoE-/-mice showed significantly increased lipid levels(P<0.01)and atherosclerosis index,obvious thickening,lipid aggregation,and collagen fiber hyperplasia in the aorta,and significantly reduced expressions of FDX1,LA,LIAS,and ACO2(P<0.05).Conclusion Serum FDX1 and LA levels decrease with worsening of coronary artery lesions,and theirs expressions are correlated with coronary artery lesions induced by hyperlipidemia.

Objective To analyze the correlation of copper death inducer ferredoxin 1(FDX1)and lipoic acid(LA)with the occurrence and severity of coronary atherosclerosis and explore their roles in coronary heart disease(CHD).Methods We analyzed the data of 226 patients undergoing coronary artery angiography(CAG)in our hospital between October,2021 and October,2022,including 47 patients with normal CAG findings(control group)and 179 patients with mild,moderate or severe coronary artery stenosis(CHD group).Serum FDX1 and LA levels were determined with ELISA for all the patients.We also examined pathological changes in the aorta of normal and ApoE-/-mice using HE staining and observed collagen fiber deposition with Sirius red staining.Immunohistochemistry was used to detect the expression and distribution of FDX1 and LA in the aorta,and RT-PCR was performed to detect the expressions of FDX1,LIAS and ACO2 mRNAs in the myocardial tissues.Results Compared with the control patients,CHD patients had significantly lower serum FDX1 and LA levels,which decreased progressively as coronary artery stenosis worsened(P<0.01)and as the number of involved coronary artery branches increased(P<0.05).Serum FDX1 and LA levels were positively correlated(r=0.451,P<0.01)and they both negatively correlated with the Gensini score(r=-0.241 and-0.273,respectively;P<0.01).Compared with normal mice,ApoE-/-mice showed significantly increased lipid levels(P<0.01)and atherosclerosis index,obvious thickening,lipid aggregation,and collagen fiber hyperplasia in the aorta,and significantly reduced expressions of FDX1,LA,LIAS,and ACO2(P<0.05).Conclusion Serum FDX1 and LA levels decrease with worsening of coronary artery lesions,and theirs expressions are correlated with coronary artery lesions induced by hyperlipidemia.

Objective To investigate the clinical effect of coronal bone structure matching(CBSM)in the treatment of dis-tal radius fracture.Methods A total of 39 cases of distal radius fracture between Jannary 2018 and Jannary 2022 were included in this study.Among them there were 22 males and 17 females with an average age of(48.9±16.3)years old,ranged from 22 to 65 years old.All patients were treated with open reduction and internal fixation with plates.Based on the measurement of CB-SM value on the X-ray film the next day after surgery.All patients were divided into matched group and mismatched group ac-cording to the coronal bone structure matching in the normal range or not.There were 27 patients in the matched group,includ-ing 15 males and 12 females,the age ranged from 22 to 64 years old with an average of(48.0±16.2)years old.AO classifica-tion of fracture was C1 in 6 cases and C2 in 21 cases;the operation time ranged from 1 to 6 days after injury;9 cases were com-plicated with ulnar styloid process fracture.There were 12 patients in the mismatched group,including 7 males and 5 females;the age ranged from 22 to 65 years old with an average of(48.8±15.8)years old.AO classification of fracture was C1 in 4 cases and C2 in 8 cases;the time from injury to operation ranged from 1 to 5 days;4 cases were complicated with ulnar styloid pro-cess fracture.The X-ray films were used to evaluate fracture healing,humeral height,ulnar angle and palm tilt angle at 3 months after operation.The range of wrist motion(pronation,supination,palmar inclination and dorsiflexion),function out-comes(Gartland-Werley score)and pain levels(visual analogue scale,VAS)were compared between the two groups at the last follow-up.Results The average follow-up time of 39 patients were(9.5±4.3)months,ranged from 6 to 14 months.All pa-tients healed in one stage without postoperative infection,fracture nonunion and fracture displacement occurred.Compared with match group at the last follow-up,the VAS in the mismatch group was increased[(2.5±1.3)points vs(1.6±1.0)points],the wrist pronation were decreased[(70.5±12.6)° vs(80.5±9.4)°],with statistically significant difference(P＜0.05).There was no sig-nificant difference in the range of motion(supination,palmar inclination,dorsiflexion)and excellent good rate between the two groups at last follow-up after operation(P＞0.05).Conclusion Wrist dysfunction,limited pronation,and wrist pain may occur when the postoperative matching degree of the distal radius fracture is not within the normal range.

This study was aimed at understanding the trends in,and scope of,severe fever with thrombocytopenia syndrome(SFTS)in Nanjing,analyzing the spatial distribution pattern,detecting high incidence cluster areas and key popula-tions,and scientifically guiding prevention and control strategies and measures.We obtained data on SFTS cases from 2010 to 2023 in Nanjing from the China Disease Control and Prevention Information System,and described the time,popu-lation,and spatial distribution characteristics.We used joinpoint regression to calculate the annual percentage change(APC)in incidence,then used FleXScan spatial clustering scan analysis to explore spatial clustering areas at the street level.A total of 507 SFTS cases were reported from 2010 to 2023 in Nanjing.The APC was 31.8％(95％CI:22.5％-41.9％,P＜0.001),and the reported incidence in 2023 was 1.42/100 000(134 cases).The seasonal indices from May to August were 2.7,2.1,3.0,and 1.3,respectively,accounting for 76.1％of the total cases.The median age was 66(IQR:55,73)years,which gradually increased from 59 years in 2010-2011 to 68 in 2022-2023(P＜0.001);94.1％of cases were in individuals 45 years or older.Farmers,homemakers/unemployed individuals,and retirees accounted for 90.1％.The epidemic area increased from 11 streets in four districts in 2010-2011 to 58 streets in 11 dis-tricts in 2022-2023.Except for 2012-2013,global spatial autocorrelation analysis showed positive Moran's I values(0.224-0.526,P＜0.001),and FlexScan scan indicated that several streets in Lishui District and Jiangning District were the most likely clusters.Four streets in Pukou District were the secondary clusters from 2018 to 2023,and three streets in Luhe District in 2022-2023 were the secondary clusters(all P＜0.05).The reported incidence of SFTS in Nanjing showed a rapid upward trend,with spread of epidemic areas.The spatial distribution pattern was clustered.Strengthened training in diagnosis and treatment technology and detection ability of medical institutions,surveillance in high-incidence areas,tracing of case flow,and health education of tick and disease prevention knowledge are recommended.