ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

ObjectiveTo investigate the effect and mechanism of Qingre Sanzhuo decoction in treating gouty arthritis （GA） combined with hyperuricaemia （HUA）. MethodsSixty male SD rats were randomized into normal， model， colchicine （0.5 mg·kg^-1）， and low-， medium-， and high-dose （17， 34， 68 g·kg^-1， respectively） Qingre Sanzhuo decoction groups （n=10）. The rats in other groups except the normal group were treated with the modified method for the modeling of GA combined with HUA. The drug intervention groups were administrated with corresponding drugs by gavage in the afternoon every day and the normal group and the model group were administrated with an equal volume of sterile normal saline by gavage. The level of uric acid （SUA） in the serum was measured 2 h after the last administration. The degree of ankle joint swelling was calculated 0.5， 12， 24， 48 h after modeling， and joint inflammation was scored. The pathological changes of ankle joints were observed by hematoxylin-eosin staining， and the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， C reactive protein （CRP）， and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay. Real-time PCR was performed to determine the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， gasdermin D （GSDMD）， and nuclear factor-kappa B （NF-κB） in the synovial tissue of ankle joints. Western blot was employed to determine the protein levels of NLRP3， ASC， and Caspase-1 in ankle joints. The immunohistochemical method was used to detect the expression of GSDMD and NF-κB in the synovial tissue of ankle joints. ResultsCompared with the normal group， the model group showed increased SUA in the serum （P<0.05）， ankle joint swelling and joint inflammation （P<0.05）， increased number of blood vessels in the synovium， inflammatory cell foci in the synovial bursa， elevated serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and up-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. Compared with the model group， the medium- and high-dose Qingre Sanzhuo decoction groups showed reduced SUA in the serum （P<0.05）， alleviated ankle joint swelling and joint inflammation （P<0.05）， lowered serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and down-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. However， in terms of ameliorating the pathological changes of ankle joints， only the high-dose Qingre Sanzhuo decoction group showed normal morphology of the synovial membrane of ankle joints and no obvious lesion in the articular cartilage. ConclusionQingre Sanzhuo decoction may play a role in preventing and controlling GA combined with HUA by down-regulating the activity of NLRP3/ASC/Caspase-1 pathway and inhibiting the expression of inflammatory cytokines， such as TNF-α， IL-1β， CRP， and IL-18.

OBJECTIVE To systematically evaluate medication risk prediction models for hospitalized adult patients and provide references for their development and clinical application. METHODS Databases including PubMed， Embase， Web of Science， CNKI， Wanfang data， VIP and CBM were searched for studies on medication risk prediction models from their inception to May 2024. After screening the literature， extracting data， and evaluating the quality of the literature， descriptive analysis was performed on the results of the included studies. RESULTS A total of 13 studies were included， involving 12 models. Nine studies used Logistic regression algorithm for modeling， and the number of included predictive factors ranged from 3 to 11； the area under the receiver operating characteristic curve ranged from 0.65 to 0.865. The literature quality evaluation results showed that 10 studies had high risk of bias； 10 studies had high applicability risk. A total of 31 predictive factors were extracted， including 15 items of basic patient information， 3 test indicators， and 5 items of medication information， and 8 others. CONCLUSIONS The existing medication risk prediction models for hospitalized adult inpatients are mainly Logistic regression algorithm， with predictive factors mainly focusing on basic indicators such as demographics. The overall prediction performance of the models needs to be improved， and the overall risk of bias is relatively high.

Objective:To investigate the differences and prognostic value of serum myeloid-related proteins 8 and 14 (Mrp 8/14) in patients with acute respiratory distress syndrome (ARDS) induced by pulmonary and extrapulmonary sepsis.Methods:A retrospective cohort study was conducted to collect the general clinical data of septic ARDS patients admitted to the intensive care unit (ICU) of Nanjing Hospital of Nanjing Medical University from August 2021 to February 2024. The serum levels of Mrp 8/14 were detected within 24 hours after admission. According to whether the patients died during ICU stay, the patients with pulmonary ARDS and extrapulmonary ARDS induced by sepsis were divided into survival and death groups, respectively. The differences of Mrp 8/14 and other clinical data between the two groups were compared. Logistic regression analysis was used to analyze the prognostic factors of septic patients with pulmonary ARDS and extrapulmonary ARDS. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of serum Mrp 8/14 for the prognosis of patients with pulmonary ARDS and extrapulmonary ARDS.Results:A total of 138 patients with sepsis-induced ARDS were enrolled in this study, including 79 patients with pulmonary ARDS and 59 patients with extrapulmonary ARDS. Compared to the death group, the level of serum Mrp 8/14 was significantly lower [Mrp 8/14: 22.90 (17.91, 30.88) μg/mL vs. 10.73 (7.15, 17.20) μg/mL, P<0.05]. Multivariate logistic regression analysis demonstrated that the serum Mrp 8/14 level was an independent risk factor for the prognosis of pulmonary ARDS patients only during the ICU stay ( OR=1.253, 95% CI: 1.110-1.414, P<0.05). ROC curve analysis showed that the area under the curve of serum Mrp 8/14 for the prediction of death in ARDS patients with pulmonary sepsis during ICU stay was 0.855 (95% CI: 0.773-0.938, P<0.05), the cut-off value was 19.230 μg/mL, the sensitivity was 0.718, the specificity was 0.925, and the Yonden index was 0.405. Conclusion:Serum Mrp 8/14 is an effective prognostic indicator for the mortality of ARDS patients with pulmonary sepsis during ICU hospitalization.

Objective To explore the correlation between serum vitamin D(VD3)level differences and immune inflammatory markers in elderly sepsis patients.Methods A total of 103 elderly patients with sepsis(aged 65-99 years)in the ICU of the First Affiliated Hospital of Kunming Medical University from January 2020 to December 2022 were collected and divided into two groups according to the diagnostic criteria for VD3 deficiency:VD3 deficiency group(n=32)and VD3 severe deficiency group(n=71).Correlation analysis was conducted by comparing the differences in serum 25-(OH)-D3(VD3)levels,immune function-related indicators upon admission(blood routine,infection-related proteins,combined detection of 12 cytokines,absolute count analysis of lymphocytes and subgroups,quantitative determination of infection-related immune cells,immunoglobulin,and complement),illness severity,and prognostic indicators(APACHE-II score,SOFA score,duration of ICU stay,and 28-day mortality rate).Result(1)Serum VD3 levels were lower in elderly patients with sepsis.No patient was in the VD3 normal or insufficient group.Patients with severe VD3 deficiency had higher APACHE-II scores,SOFA scores,and 28-day mortality rates than those with VD3 deficiency,and these scores were negatively correlated with serum VD3 levels(P<0.001),while the difference in ICU stay duration between the two groups was not statistically significant(P>0.05);(2)WBC,PCT,CRP,and CD4/CD8 in the VD3 deficiency group were all lower than those in the VD3 severe deficiency group(P<0.05),while IL-6,IL-10,CD45+,CD3+/CD45+,and CD19+Abs were all higher than those in the VD3 severe deficiency group(P<0.05);In the VD3 deficiency group,VD3 levels were positively correlated with CD45+(P<0.05 for all),while negatively correlated with IL-6,IL-10,PCT,and CRP(P<0.05 for all);In the VD3 severe deficiency group,there were fewer corre-lation indicators and the correlation strength was not as strong as that in the VD3 deficiency group.Conclusion(1)Elderly patients with sepsis generally have lower levels of VD3,with lower levels associated with more severe illness and poorer prognosis;(2)In elderly sepsis patients,compared to patients with severe VD3 deficiency,patients with VD3 deficiency have lower levels of inflammation,stronger cellular immune response,and stronger correlation,suggesting that the effects of different VD3 levels on immune inflammatory responses may vary in elderly sepsis patients.

Objective To analyze the correlation between the duration of hyperbaric oxygen(HBO)therapy and oral medication clonazepam reduction in patients with paroxysmal sympathetic hyperactivity(PSH).Methods Clinical data of patients with secondary PSH after severe brain injury at Capital Medical University Affiliated Fuxing Hospital from September 2017 to July 2023 were retrospectively included,covering general information,etiology,lesion location,comorbidities,vital signs at admission,PSH attack characteristics,HBO treatment frequency,PSH treatment drugs and dosage.According to the number of HBO treatments,PSHpatients were divided into HBO short course group(10 treatments)and HBO long course group(＞10 treatments).Multiple logistic regression and rank correlation analysis were used to investigate the correla-tion between the duration/frequency of HBO treatment and the reduction of clonazepam.Results A total of 75 PSH patients who met the inclusion and exclusion criteria were selected,including 38 cases(50.7％)who re-ceived reduced doses of clonazepam.There were 32 cases(42.7％)in the HBO short course group and 43 ca-ses(52.3％)in the HBO long course group.The reduction rate of clonazepam in the HBO short course group was lower than that in the HBO long course group[31.3％(10/32)vs.65.1％(28/43),crude OR=4.11(95％CI:1.55-10.90),P=0.004].After adjusting for confounding variables,a multivariate Logistic re-gression model showed a significant correlation between HBO long course and clonazepam reduction(OR=3.76,95％CI:1.23-11.55,P=0.021).Rank correlation analysis showed a positive correlation between HBO treatment frequency and clonazepam reduction(rs=0.331,P=0.004).Conclusions Long course HBO treatment was positively correlated with oral reduction of clonazepam in PSH patients,which may help re-duce the side effects caused by clonazepam and become a non-pharmacological treatment option for PSH.

Osteosarcoma(OS)is a common primary malignant bone tumor with high mortality,disability,metastasis,and recurrence rates and a complex pathogenesis,Resulting in serious effects on patient quality of life and huge economic burdens on families and society.Traditional Chinese medicine(TCM)has"multi-target,multi-component and multi-pathway"characteristics.Recent studies using animal and cell models demonstrated that the mechanism of OS progression was related to Notch,mitogen-activated protein kinase,Wnt/β-catenin,phosphatidylinositol 3-kinase/AKT,Hedgehog and nuclear factor-κB,transforming growth factor-β/Smad and signal transducer and activator of transcription pathways.TCM can exert anti-tumor effects by influencing biological processes such as cell proliferation,migration,invasion,apoptosis,and autophagy via interfering with the above signaling pathways.This review considers the roles of these signaling pathways in OS and summarizes the current research status of TCM interventions in the prevention and treatment of OS,with the aim of providing a reference for future studies of TCM treatments of OS and to provide new ideas for its clinical treatment.

AIM:To investigate the therapeutic effect of Qingre sanzhuo decoction on rats with hyperuri-caemia combined with gouty arthritis and its effect on TLR4/Myd88/NF-κB signalling pathway.METHODS:Forty-eight SD male rats were randomly divided into blank,model,and colchicine groups(0.3 mg·kg-1·d-1),and Origre sanzhou decotion low,medium and high-dosage groups(7.42,14.85,29.70 g·kg-1·d-1),which were treated with the modified Coderre method for hyperuricemia combined with acute gouty arthritis via gavage of yeast paste combined with potassium oxa-late,which was used for the treatment of acute gouty arthritis combined with hyperuricemia.A composite rat model of acute gouty arthritis was constructed by combining yeast paste with potassium oxalate gavage to cause hyperuricaemia,combined with the modified Coderre method.After 7 days of intervention,the circumference of the right ankle joint of rats was measured and the swelling of the ankle joint was calculated,the blood uric acid(HUA)level of rats was determined by biochemical method,the histopatho-logical and morphological changes of the synovial membrane of the ankle joint of rats were examined by HE staining,and the serum levels of inflammatory factors,tumour necrosis factor-alpha(TNF-α),inter-leukin-6(IL-6),and IL-1β were determined by enzyme-linked immunosorbent assay(ELISA),and Western blotting was performed to determine the levels of inflammatory factors,TNF-α,and IL-1β.The protein expression levels of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(Myd88),and nuclear factor-κB(NF-κB)in the synovial tissues of the ankle joints of the rats were determined by Western blot method,and the mRNA expression of TLR4,Myd88,and NF-κB in the rat was determined by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR).RESULTS:Compared with the blank group,rats in the model group showed significantly lower ankle joint swelling(P<0.01),increased levels of HUA,dis-organised synovial tissue structure,large number of inflammatory cells infiltration,and significantly higher serum levels of TNF-α,IL-6,and IL-1β(P<0.01),and the protein and mRNA expression levels of TLR4,Myd88,and NF-κB in the synovial membrane of the ankle joints of the model group were significantly increased(P<0.01).levels were significantly increased(P<0.01);compared with the model group,joint swelling was significantly reduced in the colchicine group,and the medium-and high-dose groups of Qingre sanzhuo decoction(P<0.05);synovial hyperplasia and inflam-matory cell infiltration were improved in the colchicine group and the medium-and high-dose groups of Qingre sanzhuo decoction,and the HUA and the levels of TNF-α,IL-6,and IL-1β were significantly decreased in the dosing groups(P<0.05,P<0.01),and compared with the model group,the medium-and high-dose groups of Qingre sanzhuo decoction could significantly reduce the expression of TLR4,Myd88,and NF-κB protein and mRNA(P<0.01).CONCLUSION:Qingre sanzhuo decoction reduces the release of inflamma-tory factors by inhibiting the TLR4/Myd88/NF-κB pathway,and plays a role in the treatment of hyper-uricaemia combined with gouty arthritis.

Objective To compare the clinical efficacy of unilateral biportal endoscopy(UBE)and percutaneous transforaminal endoscopic discectomy(PTED)in treatment of far lateral lumbar disc herniation(FLLDH).Method A retrospective analysis was conducted on 42 patients with FLLDH who underwent surgery from March 2021 to March 2023.The UBE group included 18 patients,and the PTED group included 24 patients.The surgery duration,intraoperative fluoroscopy times,length of hospital stay,perioperative complications were recorded and compared between the two groups.The degree of pain was evaluated by visual analogue scale(VAS)score for pain,the Oswestry disability index(ODI)for dysfunction was used,and the Macnab scoring standard was used to evaluate the clinical efficacy.Result The operation time of the UBE group was(95.56±20.94)min,which was longer than that of the PTED group(78.25±17.23)min,and the intraoperative blood loss was(69.17±8.95)mL,which was more than that of the PTED group(23.96±5.89)mL,the differences were statistically significant(P<0.05).The hospitalization time of the UBE group was(5.67±1.28)d,compared with that of the PTED group(5.33±1.05)d,the difference was not statistically significant(P>0.05).The intraoperative fluoroscopy times in the UBE group was(3.00±0.77)times,which was significantly less than that in the PTED group(7.42±0.93)times,and the difference was statistically significant(P<0.05).The VAS score and ODI of the two groups of patients after the operation were significantly lower than those before the operation,and the differences were statistically significant(P<0.05).Three days after the operation,the VAS score of leg pain in the UBE group was(3.28±0.58)and ODI was(41.17±4.30)%,which were significantly lower than those in the PTED group(4.13±0.74)and(45.50±3.91)%,and the differences were statistically significant(P<0.05).However,when comparing the VAS score and ODI of the two groups 3 months and one year after the operation,the differences were not statistically significant(P>0.05).There was no statistically significant difference in the excellent and good rate between the two groups of patients(88.9%vs 87.5%,P=0.563).Two cases of nerve injury occurred in the PTED group,while no nerve injury was reported in the UBE group.No infections,recurrences,or major bleeding complications occurred in either group.Conclusion Both PTED and UBE are safe and effective for treatment of FLLDH.There is less intraoperative fluoroscopy time,clearer endoscopic view,and significantly lower risk of nerve injury in UBE.