ObjectiveBased on the clinical characteristics of chronic gouty arthritis （CGA） in both traditional Chinese and western medicine， this study aims to systematically evaluate the clinical concordance of existing CGA animal models， providing recommendations for establishing animal models that align with the pathological characteristics of CGA and the manifestations of traditional Chinese medicine syndromes. MethodsBy comprehensively retrieving Chinese and international databases such as China National Knowledge Infrastructure， Wanfang， VIP Chinese Science and Technology Periodical Database （VIP）， and PubMed， all relevant literature on CGA animal models was collected. Based on the guidelines， the diagnostic criteria of both traditional Chinese and western medicine were summarized and organized. The evaluation indicators for the CGA model were constructed with reference to existing evaluation modes， and the CGA animal models were analyzed to systematically evaluate the clinical concordance of existing models. ResultsThe current methods used to construct CGA animal models mainly include monosodium urate crystal induction， high-protein diet induction （poultry lack urate oxidase）， and high-fat diet combined with urate oxidase inhibitors and joint injection. Based on 11 pieces of included literature， the traditional Chinese and western medicine scoring data of each model were extracted， and the average scoring values of all models were ultimately calculated. The results show that the average clinical concordances of existing CGA animal models in both traditional Chinese and western medicine are 43.33% and 64.44%， respectively. Among them， the model with the highest clinical concordance rate is the one with a high-fat diet combined with potassium oxonate to induce hyperuricemia plus joint injection， achieving 83.33% clinical concordance in western medicine and 60% in traditional Chinese medicine. This model aligns well with the pathogenic characteristics and pathological changes of clinical CGA. ConclusionAlthough current CGA animal models can simulate some pathological characteristics of CGA， they struggle to comprehensively reflect the complex pathological processes of CGA and the characteristics of traditional Chinese medicine syndromes. Therefore， in the future， it is necessary to establish the CGA animal models that incorporate the clinical disease and syndrome characteristics of traditional Chinese and western medicine and formulate the uniform model evaluation criteria， providing more precise tools for CGA mechanism research and the development of traditional Chinese medicine.

ObjectiveTo evaluate the therapeutic effect of Huazhuo SanJie Chubi presciption （HSCD） on chronic gouty arthritis （CGA） rats with low-grade inflammation and to explore the underlying mechanism with a focus on macrophage polarization. MethodsThe 41 male 6-week-old SD rats were randomly allocated， using the random number table， to a normal group （n=8） and a model group （n =33）. CGA with low-grade inflammation was induced in the model group by daily gavage of potassium oxonate （250 mg·kg^-1·d^-1） and hypoxanthine （300 mg·kg^-1·d^-1）， combined with intra-articular injection of a monosodium urate （MSU） crystal suspension （50 μL， 25 g·L^-¹） into the left ankle twice weekly. After 4 weeks of modeling， 3 rats were randomly selected from each group for model validation. The remaining successfully modeled rats were randomly divided into a model group， an HSCD group （10.35 g·kg^-1·d^-1， gavage once daily）， an M1 polarization agonist group （L-methionine sulfoximine， 300 mg·kg^-1， subcutaneous injection every other day）， an M1 polarization agonist + HSCD group， an M2 polarization inhibitor group （PD0325901， 10 mg·kg^-1·d^-1， gavage once daily）， and M2 polarization inhibitor + HSCD group. The corresponding drug or drug combination was administered according to group assignment， whereas rats in the normal and model groups received 0.5% carboxymethyl cellulose sodium （CMC-Na） vehicle （10.35 g·kg^-1·d^-1， gavage once daily）. All interventions were continued for four weeks. During the intervention period， except for the normal group， potassium oxonate （250 mg·kg⁻¹） and hypoxanthine （300 mg·kg^-1） were co-administered by gavage every other day to maintain the model. At the end of treatment， serum uric acid （SUA）， ankle joint diameter and joint swelling index were measured. The levels of high-sensitivity C-reactive protein （hs-CRP）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， chemokine C-C motif ligand 2 （CCL2）， S100 calcium-binding protein A8/A9 （S100A8/A9）， interleukin-10 （IL-10） and arginase-1 （Arg-1） in serum and joint fluid were determined by enzyme-linked immunosorbent assay （ELISA）. High-frequency ultrasound was used to assess MSU deposition in the ankle joint. Hematoxylin-eosin （HE） staining was performed to evaluate synovial histopathological changes. Quantitative Real-time PCR and immunofluorescence were used to detect the mRNA and protein expression of the M1 macrophage polarization markers inducible nitric oxide synthase （iNOS） and the M2 macrophage polarization marker scavenger receptor cysteine-rich type 1 protein M130 （CD163） in synovial tissue. ResultsCompared with the normal group， the model group showed significantly elevated SUA level and joint swelling index， and increased levels of pro-inflammatory cytokines， CCL2， and S100A8/A9 in both serum and joint fluid （P<0.05）， accompanied by MSU deposition and synovial inflammation in the ankle joint. The mRNA and protein expression levels of macrophage polarization M1/M2 markers iNOS and CD163 in synovial tissues were also significantly up-regulated （P<0.05）. Compared with model group， rats in HSCD group had significantly lower SUA levels， attenuated joint swelling， reduced serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in both serum and joint fluid， accompanied with alleviated MSU deposition and synovial inflammation （P<0.05）. HSCD markedly downregulated the mRNA and protein expression of M1 marker iNOS （P<0.05）， whereas it had no significant effect on the expression of M2 marker CD163. Compared with the M1 polarization agonist group， the M1 polarization agonist + HSCD group showed significantly reduced joint swelling， lower serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in joint fluid （P<0.05）. In addition， synovial inflammatory cell infiltration and angiogenesis were attenuated， and iNOS mRNA and protein expression levels were significantly reduced （P<0.05）. Compared with the M2 polarization inhibitor group， the M2 polarization inhibitor + HSCD group exhibited reduced joint swelling， decreased levels of CCL2 and S100A8/A9 in joint fluid and ameliorated synovial inflammation （P<0.05）， whereas the levels of anti-inflammatory mediators （IL-10， Arg-1） and CD163 mRNA and protein expression were not significantly increased. ConclusionHSCD alleviates low-grade inflammation in CGA rats， at least in part， by inhibiting macrophage polarization toward the M1 phenotype.

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.

Liver transplantation is a radical treatment for progressive and irreversible end-stage liver disease. However, its clinical application has always been restricted by the core bottleneck of donor liver shortage. Living donor liver transplantation can alleviate the shortage of donor livers to a certain extent, but it requires simultaneous assurance of sufficient residual liver volume in donors to avoid liver insufficiency, as well as an adequate graft-to-recipient weight ratio to prevent small-for-size syndrome, which limits its clinical application. Dual-donor liver transplantation utilizes partial liver tissues from two donors as grafts. While ensuring donor safety, avoiding small-for-size syndrome in recipients, and expanding the donor pool, this technique significantly improves the utilization rate of donor livers and effectively eases the clinical contradiction of donor liver shortage. Based on recent domestic and international clinical practices and the latest diagnosis and treatment guidelines, this article systematically reviews the developmental background, donor and recipient evaluation and selection, surgical procedures and postoperative complications of dual-donor liver transplantation, aiming to provide references for the standardized promotion and clinical optimization of this technique.

[Objective]To briefly examine the work Shanghan Leizheng by SONG Yungong,a medical scholar in Jin Dynasty,and deeply explore his academic thoughts,with the aim of providing references for clinical practice.[Methods]Taking the 50 chapters of Shanghan Lei Zheng as the research subjects,while also integrating the articles from Treatise on Febrile Diseases,this study systematically organizes the academic thought characteristics of the book by using literature research methods.[Results]Shanghan Leizheng was a kind of exerting works of Treatise on Febrile Diseases edited by SONG Yungong,a doctor in Jin Dynasty.The book consisted of three volumes,divided into 50 categories,484 methods,using sub-items of the Treatise on Cold Damage Diseases research and was printed in the form of tables,with concise,novel format.The academic thoughts of the book were mainly embodied in four aspects:Syndrome was classified by symptoms,attention should be paid to the induction and differentiation of fever and self-sweating syndrome;Master the main syndrome,integrate three levels of syndrome,syndrome and main symptoms,main syndrome,not only pay attention to the subtle differentiation of the similar main symptoms,but also emphasize the important role of different concurrent and pulse syndromes in the diagnosis of the same main symptoms;Prescription corresponding to syndrome,what kind of syndrome with what kind of prescription,no corresponding syndrome,remove the corresponding Chinese medicine;Different treatments for the same disease and different diseases with the same treatment,according to the main symptoms and concurrent syndromes,pulse syndromes reflect the pathogenesis of the same or not,decide whether to use the same prescription;The combination of Taoism and medicine,practicing medicine and with determination,investigating things,worship teachers and then enter the portal of medicine;Adhering to the classics and inheriting the viewpoints of Plain Questions:Heat Syndrome,which served as the theoretical support of the entire book.[Conclusion]Shanghan Leizheng pioneered the study of Treatise on Cold Damage in the form of charts,which was of pioneering significance and embodied a spirit of innovation.On the basis of ZHANG Zhongjing's diagnostic and treatment system of"disease-pulse-symptom-treatment",it expanded to"disease-symptom-primary symptom-additional symptom-pulse-treatment",with distinct academic characteristics and extensive clinical value.

Objective:To investigate the clinical manifestations, histological features, immunophenotype, molecular characteristics, and treatments of uterine inflammatory myofibroblastic tumor (UIMT).Methods:Clinical and pathological data of 4 UIMT cases diagnosed at the Peking Union Medical College Hospital, Beijing, China from 2020 to 2024 were collected. Their clinicopathological and genetic characteristics were analyzed.Results:The patients′ ages were 63, 42, 53 and 37 years, respectively. The tumors were located in the submucosa and intermuscular walls of the uterus, with a diameter ranging from 1.5 to 6.0 cm. All tumors were suspected by the clinician as leiomyosarcoma. Histologically, 3 of the 4 tumors showed spindle cells that appeared like leiomyoma. Prominent myxoid stroma and inflammatory cells infiltration were observed, with mitotic figures of 1-2 per 10 high-power fields. One case was primarily composed of spindle cells arranged in fascicles, with inflammatory cell infiltration, inconspicuous myxoid stroma and mitotic figures of 3 per 10 high-power fields. Two cases exhibited a pushing pattern of invasion and slightly unclear boundaries, while the other two showed infiltrative growth with unclear boundaries. The immunohistochemistry revealed diffuse and strong, cytoplasmic granular staining of ALK in all 4 cases. RNA sequencing was performed in 3 cases, of which 2 cases showed ALK gene rearrangements, and 1 case did not. One case underwent FISH testing and showed ALK gene translocation. Follow-up showed that no recurrence or metastasis was observed after surgery in all patients.Conclusions:UIMT is a rare mesenchymal tumor of the uterus and lacks specific clinical manifestations. When tumor cells exhibit mild atypia, indistinct borders, myxoid stroma, inflammatory cell infiltration, and decreased expression of ER and PR on immunohistochemistry, immunohistochemical staining of ALK is recommended to confirm the diagnosis of UIMT. This tumor shares many features with myogenic tumors and endometrial stromal sarcomas. Molecular testing may also be needed to assist in diagnosis when necessary. For patients who are not suitable for surgery or have recurrence and metastasis, targeted therapy with ALK inhibitors can be used.

Objective:To analyze the correlation between variants in the start codon of the α-globin gene and phenotypes of thalassemia, so as to provide a basis for the diagnosis and prevention of α-thalassemia.Methods:A retrospective study was conducted on 7 patients diagnosed by Yangjiang People′s Hospital and Guangzhou Hybribio Co. Ltd., from June 2019 to October 2022. Routine blood tests and hemoglobin electrophoresis were carried out. Potential variants were identified through polymerase chain reaction (PCR) combined with Reverse dot blotting (RDB), Gap-PCR, and Sanger sequencing. This study has been approved by the Medical Ethics Committee of People′s Hospital of Yangjiang (Ethics No: 20240001).Results:For the 7 patients, results of blood routine test of one case was unknown, and that of another was normal. The remaining 5 cases had presented with microcytic hypochromic anemia. The results of hemoglobin electrophoresis showed that one case had normal Hb A and slightly lower Hb A 2, whilst another had significantly decreased Hb A and Hb A 2, in addition with the appearance of a Hb H band. The content of Hb Bart′s in four neonates was ≥0.4%. The remaining one case had no result. Genetic testing has identified 4 rare start codon mutations, namely HBA2: c. 2delT, HBA2: c. 1A>G, HBA2: c. 1A>T, and HBA1: c. 2T>C. Among these, Patient 1 had harbored compound heterozygous variants of HBA2: c. 427T>C (Hb CS) and HBA2: c. 2delT. Patient 4 had harbored compound heterozygous variants of HBA2: c. 1A>G and Southeast Asian type deletion. Conclusion:Heterozygotes with HBA start codon variants usually present as silent or mild thalassemia, and the symptoms of anemia may deteriorate when combined with other α-thalassemia variant. The HBA2: c. 1A>T start codon variant was unreported previously in China. The detection of start codon variants has helped to clarify the causes of anemia, genetic counseling, and guidance for reproduction.

Objective:To observe the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) at different frequencies on cognitive impairment due to high-altitude hypoxia.Methods:Sixty officers and soldiers displaying cognitive impairment in a hypoxic high-altitude environment were randomly divided into 15Hz, 20Hz and 25Hz groups, each of 20. They were given rTMS at those frequencies for 30 days. Before the stimulation and after 15 and 30 days, event-related potentials, latencies of mismatched negativity (MMN) and P300 signals were recorded. The participants′ cognition was also evaluated using the Montreal Cognitive Assessment Scale (MoCA). Correlation between the electrophysiological indexes and the MoCA scores was computed.Results:After 15 days, all had shorter MMN latencies, higher total MoCA scores and better memory scores. The only significant difference among the three groups was in the average memory scores. After 15 days, MMN latency was significantly negatively correlated with the memory scores in all three groups ( r=0.44 to -0.54). Conclusions:rTMS at frequencies above 15Hz can effectively relieve cognitive impairment, especially memory dysfunction, resulting from high-altitude hypoxia.

Objective:To compare the clinical manifestations,laboratory results,and imaging features between pyogenic spondylitis(PS) and tuberculous spondylitis(TS).Methods:This was a cross-sectional study. A total of 88 patients with infectious diseases of spine(IDS) admitted to Shanghai Sixth People′s Hospital from January 2021 to December 2023 were analyzed,including 61 PS cases(PS group) and 27 TS cases(TS group). The clinical manifestations,laboratory results,and imaging features were compared between two groups. The factors associated with PS were analyzed by multivariate logistic regression. The diagnostic efficacy for pathogen identification was compared between metagenomics next-generation sequencing(mNGS) and bacterial culture methods in PS and TS patients.Results:Compared with the TS group,the PS group had a higher age-adjusted Charlson comorbidity index(aCCI)[3.0(1.5,4.0) points vs. 2.0(1.0,3.0) points, Z=-2.189, P=0.029],shorter onset time of disease[1.0(0.8,3.0) months vs. 6.0(2.0,12.0) months,Z=-4.353, P<0.001],and higher median blood leukocyte counts and serum ferritin(SF) level(7.2×10 9/L vs. 6.3×10 9/L, Z=-2.652, P=0.008; 571.3 ng/ml vs. 266.0 ng/ml, Z=-4.773, P<0.001). The proportions of lumbar spine involvement,non-collapsed involved vertebrae,and bone bridges formed were all higher in the PS group compared to the TS group[68.8%(99/144) vs. 41.4%(29/70), χ2=14.628, P<0.001; 68.9%(42/61) vs. 18.5%(5/27), χ2=19.055, P<0.001; 41.0%(25/61) vs. 7.4%(2/27), χ2=9.921, P=0.002]. The proportions of thoracic spine involvement,severe vertebral collapse,severe narrowing of the involved intervertebral space,sequestrum,and paravertebral soft tissue calcification were all higher in the TS group compared to the PS group[52.9%(37/70) vs. 18.1%(26/144), χ2=27.463, P<0.001; 55.6%(15/27) vs. 13.1%(8/61), χ2=17.462, P<0.001; 74.1%(20/27) vs. 37.7%(23/61), χ2=9.907, P=0.002; 74.1%(20/27) vs. 18.0%(11/61), χ2=25.761, P<0.001; 51.9%(14/27) vs. 6.6%(4/61), χ2=23.599, P<0.001]. Multivariate logistic regression analysis indicated that a symptom duration<5.5 months( OR=30.644,95% CI: 2.022-464.529, P<0.05) and a leukocyte count>7.35×10 9/L( OR=48.653,95% CI: 2.045-1 157.721, P<0.05) indicated a higher likelihood of PS; while the vertebral collapse indicated a higher likelihood of TS( OR=0.025,95% CI: 0.001-0.638, P<0.05). The most common pathogen in the PS group was Staphylococcus aureus(31 cases,50.8%),followed by Streptococcus species(10 cases,16.4%). The positive rates of mNGS testing in the PS and TS groups were 84.1%(37/44) and 12/13,respectively,which were higher than those of conventional bacterial culture[77.8%(42/54)] and Mycobacteriumtuberculosis culture(2/11). Conclusions:Compared with the TS patients,the PS patients have shorter onset time,higher aCCI scores,higher blood leukocyte counts and SF levels,less vertebral collapse and intervertebral space narrowing,and more bone bridge formation. The TS patients have more dead bones and calcifications. The mNGS has a higher diagnostic efficacy than bacterial cultures for PS and TS.

With the deepening understanding of the pathogenesis of psoriasis, small-molecule drugs targeting the key Janus kinase (JAK) -tyrosine kinase (TYK) 2 pathway have gained increasing interest. TYK2-related pathways play an important role in the pathogenesis of psoriasis, while they are not involved in modulating broad biological effects, making them one of the potential therapeutic targets for the efficient and safe treatment of psoriasis. How to improve the selectivity and specificity of TYK2 inhibitors to minimize adverse reactions associated with the inhibition of other pathways has been one of the key directions for development of drugs targeting TYK2 in recent years. This review summarizes the role of TYK2 pathway in the pathogenesis of psoriasis, the modes of action of TYK2 inhibitors (competitive or allosteric inhibition), and the latest clinical research progress.