Gout is a crystal-associated arthropathy caused by the deposition of monosodium urate crystals and is closely related to purine metabolic disorders and impaired uric acid excretion. It is clinically characterized by hyperuricemia， recurrent joint swelling and pain， and tophus formation. The disease course is divided into three stages： The hyperuricemia stage， acute attack stage， and chronic gouty arthritis stage. Modern medicine has reached a consensus on its pathology， but traditional Chinese medicine （TCM） lacks a systematic stage-specific understanding of gout pathogenesis and its underlying mechanisms， making it difficult to guide precise syndrome differentiation and treatment. By integrating classical TCM theory， clinical practice， and modern medical understanding， and drawing upon descriptions of Bi syndrome caused by endogenous dampness and turbidity in classical texts such as Huangdi Neijing·Ling Shu and Synopsis of the Golden Chamber， our team proposes the pathogenic concept of gout as ''endogenous dampness leading to Bi syndrome'' and the core pathogenesis of ''spleen deficiency with internal retention of dampness-turbidity''. We systematically elucidate the evolution of pathogenesis across different stages and corresponding therapeutic strategies. This study posits that metabolic byproducts such as urate fall under the category of ''endogenous pathogenic dampness-turbidity''. When genetic or dietary factors lead to metabolic abnormalities， it manifests as ''spleen deficiency with impaired transport and transformation''， resulting in ''internal retention of pathogenic dampness-turbidity''. When damp-turbidity stagnates in the blood vessels， serum uric acid levels rise. When it stagnates in the viscera and limbs， monosodium urate crystals deposit in the joints. Triggered by precipitating factors， this leads to gout attacks—the core pathological process of ''endogenous dampness leading to Bi syndrome''. Based on this theory， the stage-specific pathogenic characteristics of gout are proposed： The hyperuricemia stage is characterized by ''spleen deficiency with impaired transport and transformation， internal retention of pathogenic dampness-turbidity''， the acute attack stage is primarily marked by ''dampness-turbidity and static heat obstructing the limbs and joints''， while the chronic stage is defined by ''spleen deficiency with internal retention of pathogenic dampness-turbidity， intermingled with phlegm-stasis binding''. The treatment principle centers on ''strengthening the spleen and draining dampness'' throughout all stages. During the hyperuricemia stage， treatment focuses on ''strengthening the spleen， draining dampness， and eliminating turbidity''. In the acute attack stage， the treatment should "strengthen the spleen， drain dampness， clear heat， eliminate turbidity， alleviate swelling， and relieve pain''. In the chronic stage， the treatments emphasizes to ''strengthen the spleen， drain dampness， transform turbidity， clear heat， resolve phlegm， and activate blood circulation''. This approach has yielded favorable therapeutic outcomes in clinical practice. This theoretical system clarifies the nature of gout as ''spleen deficiency being the root， dampness-turbidity being the secondary manifestation'' and systematically analyzes its pathogenesis evolution process and characteristics. The constructed stage-based treatment protocol has been validated through clinical and basic research， providing systematic theoretical guidance and a practical framework for the precise TCM management of gout， thereby promoting the modernization of TCM pathogenesis theory related to gout.

ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription （HSCD） on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg^-1·d^-1 and potassium oxonate solution at 250 mg·kg^-1·d^-1， combined with intra-articular injection of 200 μL monosodium urate （MSU） crystal suspension at 25 g·L^-1 into the right ankle joint （joint injection once every three days）， so as to induce the gouty bone erosion model. After four weeks of modeling， three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group， HSCD group （10.35 g·kg^-1·d^-1）， allopurinol group （20 mg·kg^-1·d^-1）， and inhibitor group （LY294002， 10 mg·kg^-1·d^-1）， with six rats per group. Except for the blank group， rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg^-1 and potassium oxonate solution at 250 mg·kg^-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline （10.35 g·kg^-1·d^-1） by gavage for four consecutive weeks. After administration， ankle joint swelling of the rats in all groups was observed， and the diameters were measured. Bone volume fraction （BV/TV） and bone surface area to bone volume （BS/BV） were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin （HE） staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of receptor activator of nuclear factor-κB ligand （RANKL） and phosphorylated （p）-phosphatidylinositol-3-kinase （PI3K） in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion， including RANKL， tartrate-resistant acid phosphatase （TRAP）， cathepsin K （CTSK）， and matrix metalloproteinase-9 （MMP-9） in the ankle joint tissues of rats were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of the proteins related to the bone erosion， including RANKL， CTSK， TRAP， MMP-9， and the proteins related to the PI3K/protein kinase B （Akt） signaling pathway， including PI3K， Akt， mammalian target of rapamycin （mTOR）， p-PI3K， phosphorylated protein kinase B （p-Akt）， and phosphorylated mammalian target of rapamycin （p-mTOR）， were detected by Western blot. ResultsCompared with the blank group， the modeling group showed marked ankle swelling and increased diameter. Micro-CT revealed an uneven articular surface and honeycomb-like bone erosion in the ankle joint. Quantitative analysis showed decreased BV/TV and increased BS/BV （P<0.05）. HE staining revealed a narrowed joint space， rough and discontinuous cartilage surfaces， reduced and unevenly distributed chondrocytes， partial hypertrophy， and blurred tidemarks， confirming successful model establishment. After four weeks of intervention， compared with those in the blank group， the rats in the model group exhibited severe ankle swelling and increased diameters （P<0.05）. Micro‑CT showed that the ankle joint surface was irregular， and bone erosion exhibited a honeycomb‑like morphology. The microstructural parameters of the bone revealed a decreased BV/TV and an increased BS/BV （P<0.05）. Histopathological examination revealed a narrowed joint space and severe articular cartilage destruction. The levels of uric acid in the serum and inflammatory factors （IL-1β， IL-6， and TNF-α） were increased （P<0.05）. The mRNA and protein levels of the proteins related to bone erosion in joint tissue， including RANKL， CTSK， TRAP， and MMP-9， were upregulated （P<0.05）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR in the proteins related to the PI3K/Akt signaling pathway were increased （P<0.05）. RANKL and p-PI3K protein fluorescence intensities were elevated （P<0.05）. Compared with those in the model group， the above indicators in all other administration groups showed varying degrees of improvement. The HSCD group and inhibitor groups exhibited more significant effects in reducing ankle swelling， improving bone erosion， bone microstructure （significant decrease in BV/TV and increase in BS/BV）， and the pathology of cartilage erosion， lowering inflammatory factor levels， downregulating the proteins related to the bone erosion， and suppressing activation of the PI3K/Akt/mTOR pathway （P<0.05）. The uric acid levels in rats' serum were reduced in both HSCD and allopurinol groups （P<0.05）. Compared with those in the HSCD group， the rats in the allopurinol group had larger ankle diameters （P<0.05）， more severe bone erosion and bone microstructure damage （P<0.05）， worse improvement of the pathology of cartilage erosion， higher levels of IL-6 and TNF-α （P<0.05）， elevated expressions of the proteins related to the bone erosion， higher expression ratio of proteins related to the PI3K/Akt signaling pathway （P<0.05）， and higher fluorescence intensities of RANKL and p-PI3K proteins （P<0.05）. The inhibitor group achieved comparable results to the HSCD group in improvements of bone microstructure and the reduction of IL-1β and IL-6， stronger suppression of TNF-α and PI3K/Akt/mTOR signaling pathway activation （P<0.05）， but weaker effects on cartilage repair and serum uric acid reduction （P<0.05）. ConclusionHSCD effectively reduces uric acid levels in serum， suppresses inflammatory factor secretion， and downregulates the expressions of proteins related to bone erosion， including RANKL， CTSK， TRAP， and MMP-9 in the joint tissues. Its action mechanism of improving gouty bone erosion may be associated with inhibition of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the whole genomic characteristics and phylogenetic relationships of clinical isolates of enteroaggregative Escherichia coli (EAEC) in diarrhea outpatients in Pudong New Area, Shanghai. MethodsBased on the diarrheal disease surveillance network in Pudong New Area, Shanghai, whole-genome sequencing was performed on a total of 55 EAEC strains isolated from fecal samples of the diarrhea outpatients from January 2015 to December 2019. The genome analyses based on raw sequencing data encompassed genome size, coding genes, dispersed repeat sequences, genomic islands, and protein coding regions, and pan-genome analyses were conducted simultaneously. Contigs sequences assays were performed to analyze molecular characteristics including serotypes, antibiotic resistance genes, and virulence factors. The phylogenetic clusters and multilocus sequence typing (MLST) were identified, and a phylogenetic tree was constructed. ResultsEAEC exhibited an open pan-genome. The predominant serotype of EAEC in diarrhea outpatients in Pudong New Area was O130:H27, and the carriage rate of β-lactam resistance genes was the highest (67.27%, 37/55). A total of 29 virulence factors and 106 virulence genes were identified, phylogenic group B1 was the predominant group, and clonal group CC31 was the dominant clonal group. The strain distribution was highly heterogeneous. ConclusionThe genomic characteristics of EAEC displayed significant strain polymorphism. It is necessary to develop effective strategies for differential diagnosis and improve detection capabilities for infection with EAEC of different serotypes and genotypes.

Salvia miltiorrhiza (S. miltiorrhiza) represents a crucial component of traditional Chinese medicine, demonstrating effects on blood circulation activation and stasis removal, and has been widely utilized in asthma treatment. This study isolated a novel phenolic acid (S1) from S. miltiorrhiza and investigated its anti-asthmatic activity and underlying mechanisms for the first time. An allergic asthma (AA) model was established using ovalbumin (OVA). The mechanism of S1's effects on AA was investigated using multi-factor joint analysis, flow cytometry, and co-culture systems to facilitate clinical asthma treatment. S1 (10 or 20 mg·kg^-1) was administered daily to mice with OVA-induced AA (OVA-AA) during days 21-25. The study examined airway responsiveness, lung damage, inflammation, and levels of immunoglobulin E (IgE), PGD2, interleukins (IL-4, 5, 10, 13, 17A), tumor necrosis factor α (TNF-α), GM-CSF, CXCL1, CCL11, and mMCP-1. Additionally, mast cell (MC) activation and degranulation were explored, along with T helper type 17 (Th17)/Treg immune cells and TLR4 pathway biomarkers. The antagonistic activity of that specific antagonist of TLR4 (TAK-242) (1 µmol·L^-1), a specific TLR4 blocker, against S1 (10 µmol·L^-1) was examined in co-cultured 16HBE cells and bone marrow-derived cells (BMDCs) or splenic lymphocytes (SLs) induced with LPS (1 µg·mL^-1) to elucidate the TLR4 pathway's mediating role. S1 demonstrated reduced airway responsiveness, lung damage, and inflammation, with downregulation of IgE, PGD2, interleukins, TNF-α, GM-CSF, CXCL1, CCL11, and mMCP-1. It also impeded MC activation and degranulation, upregulated IL-10, and influenced Th17/Treg immune cell transformation following OVA challenge. Furthermore, S1 inhibited the TLR4 pathway in OVA-AA mice, and TLR4 antagonism enhanced S1's positive effects. Analysis using an OVA-AA mouse model demonstrated that S1 alleviates AA clinical symptoms, restores lung function, and inhibits airway response. S1's therapeutic effects occur through regulation of Th17/Treg immune cells and inflammation, attributable at least partially to the TLR4 pathway. This study provides molecular justification for S1 in AA treatment.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

BACKGROUND:Patients with femoral intertrochanteric fracture may have nutritional risks during proximal femoral nail anti-rotation surgery,and a clinical predictive model is established based on nutritional assessment tools. OBJECTIVE:To establish the nomogram of the nutritional risk prediction model for patients with intertrochanteric fracture after proximal femoral nail anti-rotation fixation and evaluate the accuracy of the model. METHODS:From December 2018 to July 2022,patients with femoral intertrochanteric fractures who underwent proximal femoral nail anti-rotation fixation in First Department of Orthopedics,Second Affiliated Hospital of Baotou Medical College were selected as the study subjects.The nutritional risk status of patients was assessed using nutritional risk screening 2002.Logistic regression was used to build the model.The receiver operating characteristic curve,Calibration plot calibration curve,and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the discrimination,calibration and clinical applicability of the prediction model.The model was visualized using Nomogram diagrams. RESULTS AND CONCLUSION:(1)Seventy-six patients were included according to the inclusion criteria.The incidence of nutritional risk was 80%after being assessed using nutritional risk screening 2002.(2)The results of Logistic regression analysis demonstrated that age≥77 years old,body mass index<22.80 kg/m2,upper arm circumference<25.01 cm,hemoglobin<98.51 g/L,albumin<31.61 g/L,and prealbumin<138.56 g/L were all independent risk factors for nutritional risk(P<0.05).(3)The area under the receiver operating characteristic curve was 0.919(95%CI:0.843-0.994).(4)The results of the Hosmer-Lemeshow goodness-of-fit test displayed that nutritional risk prediction value was high.(5)It is concluded that the nutritional risk assessment model constructed in this study has a good degree of discrimination and calibration,and has a certain predictive ability,which can be used as a reference tool for nutritional risk assessment of patients after proximal femoral nail anti-rotation fixation.

Objective:To evaluate the characteristics of vaginal flora between normal and abnormal pregnant women throughout pregnancy.Methods:Vaginal swab specimens were collected from pregnant women in the first (<14 gestation weeks, GW), second (14~28 GW) and third trimester (>28 GW) in Anqing, Anhui Province from February 2018 to February 2020. Pregnant women were divided into normal and abnormal groups according to all clinical diagnosis. The sequences of 16S rRNA gene (V3-V4) from vaginal swabs were analyzed using QIIME2 platform. The differences in the dominance of Lactobacillus, community state type (CST) transition, Alpha diversity and Beta diversity were analyzed. Diversity data after log transition were used in the analysis of linear mixed model. Results:A total of 34 pregnant women (10 normal and 24 abnormal) with 102 samples were included for analysis. The composition of vaginal flora between two groups: the relative abundance of Lactobacillus was the highest at the genus level and Lactobacillus crispatus and Lactobacillus iners was the top two species with high relative abundance. The dominance of Lactobacillus, Alpha diversity and transition of CST were also similar. Both groups had a gradually decreased trend of Alpha diversity with GW, and the Chao1, Observed species and Faith′s PD indexes′ were different in different GW ( P<0.05). All Beta diversity metrics in normal group had descending trend, with lower value of the index of first distance which implied a higher microbiota stability, while Bray-Curtis, Weighted UniFrac distance had ascending trend in abnormal group, indicating lower stability. Jaccard distance′s first distance was statistically differed among GW and Unweighted UniFrac distance′s differed between normal and abnormal groups. Conclusions:The first distance of Unweighte UniFrac distance in abnormal pregnant women is higher than that of normal pregnant women and the vaginal flora in abnormal group has lower stability.

Objectives:To observe the clinical efficacy of anterior cervical V-osteotomy Y-decompression and fusion(ACVYF)for treating ossification of posterior longitudinal ligament(OPLL)in cervical spine.Meth-ods:The clinical data of 60 patients with single-segment vertebral level OPLL who underwent surgical treat ment in Luoyang Orthopedic Traumatological Hospital of He'nan Province from June 2018 to October 2022 were retrospectively analyzed.Among them,30 cases were treated with ACVYF operation(ACVYF group),in-cluding 18 men and 12 women,aged 47-65 years(61.0±6.4 years),with a body mass index(BMI)of 16.8-28.1kg/m2(23.67±2.86kg/m2)and a disease duration of 10-80 months(37.5±20.1 months),whose surgical seg-ments fell in C3 in 2 cases,C4 in 5 cases,C5 in 13 cases,C6 in 10 cases.The other 30 cases were treat-ed with anterior cervical corpectomy decompression and fusion(ACCF)operation(ACCF group),including 19 men and 11 women,aged 44-68 years(59.5±6.8 years),with a BMI of 16.6-26.4kg/m2(23.30±2.56kg/m2)and a disease duration of 13-72 months(35.8±18.8 months),whose surgical segments fell in C3 in 3 cases,C4 in 6 cases,C5 in 12 cases,C6 in 9 cases.The two groups were comparable in gender,age,BMI,disease dura-tion,surgical section and other general information with no statistical difference(P＞0.05).The operation time,intraoperative bleeding,and complications of the two groups were compared;The cervical Japanese Or-thopaedic Association(JOA)scores were recorded before operation,at 1 week,and 3,6 and 12 months after operation,and the JOA score improvement rate was calculated at postoperative 12 months;The height of the fusion area and C2-7 Cobb angle were measured on X-ray films at pre-operation,1 week,3 months,6 months and 12 months after operation.The fusion condition of implants were observed and evaluated on X-ray film or CT image at 3 months,6 months and 12 months after operation.Results:The operation was completed smoothly in both groups.The operation time and intraoperative bleeding were 88.2±19.7min and 133.3±24.4mL respectively in the ACVYF group,which were 91.5+24.1min and 137.7±29.4mL in the ACCF group,and there was no statistical difference between the two groups(P＞0.05).Three cases of dysphagia occurred in both groups after surgery,which resolved spontaneously after 1-2 weeks.No complications occurred during the follow-up period,and there was no statistically significant difference in the complication rates between the two groups(P＞0.05).The JOA scores of both groups at all time points after surgery showed significant improvement compared with those before surgery(P＜0.05),and there was no statistically significant difference between the two groups at the same time points(P＞0.05);The height of the fusion zone and C2-7 Cobb angle after operation were statistically different from those before operation(P＜0.05),and no significant difference was found between the two groups at preoperation,postoperative 1 week and 3 months(P＞0.05),while those of ACVYF group were bigger than ACCF group at postoperative 6 and 12 months(P＜0.05).The improvement rate of cervical JOA score at 12-month follow-up was(72.39±10.54)％in the ACVYF group and(75.92±10.39)％in the ACCF group,and there was no statistically significant difference between the two groups(P＞0.05).The rate of implant fusion was better in the ACVYF group at 3-month and 6-month follow-ups(70.0％and 93.3％)than in the ACCF group(40.0％and 73.3％)(P＜0.05),and both groups had osseous fusion at 12 months postoperatively(P＞0.05).Conclusions:ACVYF can effectively relieve the compression of the posterior longitudinal ligament on the spinal cord at the vertebral level and improve the neurological function of the patients;Comparing with ACCF,ACVYF can better maintain the physiological curvature of the cervical vertebrae and speed up the fusion of the implants.

Abstract OBJECTIVE To explore the material basis and mechanism of Crataegi Fructus in improving metabolic hypertension(MH) by using network pharmacology and molecular docking technique.METHODS The components of Crataegi Fructus were collected by HERB, ETCM database and literature survey; screening all ingredients of Crataegi Fructus to improve MH targets through databases such as SwissTargetPrediction and GeneCards; build "active ingredient-target-disease" network of Crataegi Fructus with Cytoscape software; DAVID was used to analyze GO enrichment and KEGG pathway. The core components and core targets were verified by molecular docking with Autodock software. RESULTS The total of 89 active components were screened from Crataegi Fructus and acted on 84 targets. Among them, the core active components of Crataegi Fructus to improve MH were maslinic acid, fomefficinic acid B, linolenic acid, linoleic acid, methyl-n-nonylketone, apigenin, ursolic acid, etc. The core targets were CYP19A1, PPARA, ESR1, PTGS2, PPARG, NR3C1, MMP9, TNF, etc. The mechanism of action mainly involved multiple signaling pathways such as inflammation, glycolipid metabolism, and vascular endothelial function. Molecular docking showed that the core active ingredients of Crataegi Fructus had high affinity with core targets. CONCLUSION Crataegi Fructus may regulate multiple signaling pathways such as TNF, IL-17, AGE-RAGE, HIF-1, cGMP-PKG through multi-component regulation, thereby inhibiting inflammatory response, improving glucose and lipid metabolism abnormalities, and improving vascular endothelial function, so as to comprehensively exert the role of improving MH in various aspects.