BACKGROUND:Rheumatoid arthritis is an inflammatory disease.Many studies have shown that wogonin has a good anti-inflammatory effect on rheumatoid arthritis,but its exact efficacy and specific mechanism of action remain to be clarified. OBJECTIVE:To investigate the mechanism of wogonin ameliorating joint inflammation by regulating endoplasmic reticulum stress pathway in rats with collagen-induced arthritis. METHODS:(1)At the animal level:Female Wistar rats were divided into healthy control group,arthritis model group and wogonin treatment group.Rat models of arthritis in the latter two groups were established by subcutaneous injection of bovine type Ⅱ collagen and adjuvant.In the wogonin group,wogonin was given by gavage for 28 consecutive days after modeling.During this period,the rats in each group were weighed,and arthritis score and ankle swelling were measured every 7 days.After the experiment,the pathological changes of the joint were observed,the mRNA and protein levels of endoplasmic reticulum stress pathway GRP78 and CHOP were detected by qRT-PCR,western blot,and immunohistochemistry.(2)At the cellular level,cell counting kit-8 was used to detect the cytotoxic effect of wogonin on fibroblast-like synoviocytes from rats with collagen-induced arthritis.The fibroblast-like synoviocytes induced by thapsigargin were treated with different concentrations of wogonin.The levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant were detected by ELISA,and the intracellular reactive oxygen species in each group were determined by DCFH-DA probe method.The mRNA and protein levels of GRP78,IRE1α,XBP1s and CHOP were detected by qRT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the healthy control group,arthritis index score and ankle swelling degree in the arthritis model group were increased(P<0.01),synovial hyperplasia,inflammatory cell infiltration,cartilage destruction and bone erosion were observed in pathological sections,and the mRNA and protein expressions of GRP78 and CHOP in the ankle were significantly increased(P<0.01),which were mainly located in synovial tissue and articular surface.Compared with the arthritis model group,the arthritis index score and ankle swelling degree in the wogonin treatment group were decreased(P<0.05),synovial hyperplasia and the number of inflammatory cells were decreased,cartilage destruction and bone erosion were alleviated,the mRNA and protein expression levels of GRP78 and CHOP in the ankle were decreased(P<0.05),particularly in synovial tissue and on the articular surface.There was no significant difference in body mass among the three groups(P>0.05).In the cell experiment,200 μmol/L wogonin significantly reduced the survival rate of fibroblast-like synoviocytes(P<0.01).Compared with the blank control group,the levels of interleukin-1β,tumor necrosis factor-α,content of reactive oxygen species,and mRNA and protein expression of GRP78,IRE1α,XBP1s,and CHOP in the thapsigargin group were significantly increased(P<0.05);compared with the thapsigargin group,50 and 100 μmol/L wogonin significantly reduced the levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant(P<0.05,P<0.01),and 100 μmol/L wogonin significantly reduced the content of reactive oxygen species(P<0.01)and down-regulated the mRNA and protein expression levels of GRP78,IRE1α,XBP1s and CHOP(all P<0.05).These results suggest that wogonin can effectively alleviate joint inflammatory responses in rats with collagen-induced arthritis,and the endoplasmic reticulum stress pathway may be the key target of its intervention.

Purpose/Significance Based on the typical use scenario of sensitive personal information in medical and health institu-tions,the implementation of the secure use of sensitive personal information is explored.Method/Process For user registration,internal utilization and interaction,medical device/wearable device collection and information disclosure and other scenarios,the paper analyzes the risk of sensitive personal information leakage,explores the application scenarios,advantages and disadvantages of various technical means such as identity authentication,access control,data encryption,data desensitization and detection audit.Result/Conclusion The application of technical means can assist medical and health institutions to further protect the security of patients'personal information.

OBJECTIVE To analyze the research status， hotspots and trends in the research of intravenous thrombolytic drugs in the treatment of acute ischemic stroke. METHODS The original studies related to intravenous thrombolytic drugs for acute ischemic stroke were collected by searching the Web of Science core database； the authors， countries/regions， institutions and keywords of the literature were visualized and analyzed using CiteSpace 6.1.R6 software. RESULTS A total of 1 810 articles were included， and the number of articles published showed an increasing trend year by year， with the United States （556 articles） having the largest number of articles， and China ranking the second （339 articles， with centrality of 0）. The most published author was Ahmed of Sweden （32 articles）， and the most published institution was the University of Calgary in Canada （80 articles）. The current research status and hotspots were mainly the application and therapeutic exploration of new thrombolytic drugs， and the frontier and development trend were the adverse prognosis of neurological deterioration and hemorrhagic transformation accompanied by intravenous thrombolytic drug treatment. CONCLUSIONS The research hotspots and frontier about intravenous thrombolytic drugs for acute ischemic stroke are mainly the third generation of intravenous tissue plasminogen activator， and the exploration of new intravenous thrombolytic drugs and their safety and effectiveness will be the future research hotspots. Chinese scholars and research teams should strengthen cooperation and exchanges with other countries， which can be strengthened by carrying out multi-center clinical trials.

Objective Tto evaluate the effect of low intensity pulsed ultrasound(LIPUS)on the migration and phagocytosis ability of lipopolysaccharide(LPS)-induced RAW264.7 macrophages and on macrophage behavior under inflammation.Methods An in vitro activated RAW264.7 macrophage model was developed using LPS.Cell viability was assessed using a CCK-8 assay to explore the effect of LIPUS on activated and inactivated macrophages.Wound healing assays were employed to measure the effect of LIPUS on macrophage migration,and the Transwell assay was employed when LPS was used as a chemoattractant.Phagocytosis ability was examined using confocal microscopy and flow cytometry by observing the FITC fluorescence signal of internalized pHrodo Green E.coli BioParticles Conjugate.Results An activated RAW264.7 macrophage model was successfully developed using 100 ng/mL LPS.LIPUS inhibited the migration of inactivated macrophages into scratch areas as well as guided cell migration.However,cell viability and phagocytosis remained unchanged.Conclusion LIPUS may inhibit RAW264.7 migration but not affect the phagocytosis ability of the macrophages.

ObjectiveTaking Shengxuebao as the model traditional Chinese medicine（TCM）， this study aims to explore the methodologies and transfer patterns in the composition changes of TCM compound preparations from liquid to solid dosage forms. MethodBased on the previously established ultra-high performance liquid chromatography（UPLC） qualitative and quantitative methods for Shengxuebao， the fingerprint profiles of three preparations of Shengxuebao（homemade decoction， commercially available granules and mixtures） were established， and nineteen components were quantitatively analyzed. The similarities of fingerprint profiles among these three preparations were assessed using the Similarity Evaluation System for Chromatographic Fingerprint of TCM（2012 edition） and the total quantum statistical moment similarity method， respectively. The molecular connectivity index （MCI） and the average molar MCI of the chemical components in the three preparations were calculated. Seventy-two MCI values across 0-8 orders， including 8 subclasses， were calculated. The average molar MCI of 0-3 orders was used to study the "imprint template" structural characteristics and transfer patterns of the medicinal component groups. ResultThe similarities of the fingerprint profile of the decoction with those of the control， granules， and mixtures were 0.971， 0.888 and 0.799， respectively， indicating that the chemical composition of the granules and mixtures differed from that of the decoction， and that the 19 components were able to basically respond to the overall situation of the component group of Shengxuebao decoction. The total mass fractions of the detectable major components in Shengxuebao decoction， granules and mixtures was measured to be 5.498 6， 2.282 0， 1.416 6 mg·g^-1， respectively. The average molar MCI of 0-3 orders showed a gradual decrease across the three preparations， with the trend of decoction>granules>mixtures， indicating subtle changes in the overall structural characteristics of the chemical components in the samples of the three preparations. ConclusionAmong the three formulations of Shengxuebao， the traditional decoction contained the highest variety and quantity of components and carried the most substantial amount of component information， with a decreasing order observed in the granules and mixtures. This study further validates that traditional decoction is a reliable and fundamental dosage form， providing a reference for the modernization of TCM dosage forms and the quality consistency evaluation of compound preparations.

Tumor-associated macrophages （TAMs）， as the main immune cells in the human body， are key factors in maintaining the homeostasis of the tumor microenvironment. With high plasticity， they can polarize into the classically activated （M1） macrophages or alternatively activated （M2） macrophages under different conditions. M1 macrophages can inhibit tumor growth by phagocytosis， and M2 can inhibit the immune microenvironment to promote tumorigenesis and immune escape. Small molecules of traditional Chinese medicine have been widely studied in gastrointestinal tumors. These small molecules exert anti-tumor activity by enhancing TAM activity and promoting the polarization of macrophages. Targeted intervention in TAMs with these molecules has the potential to inhibit the development of gastrointestinal tumors. This article summarizes the research status and significance of small molecules of traditional Chinese medicine targeting TAMs against gastrointestinal tumors， aiming to provide reference for the future studies in this field.

OBJECTIVE To prepare meloxicam solid dispersions tablets, and to investigate their dissolution in vitro. METHODS Crystal inhibition experiments were carried out to screen the carrier materials, and the solid dispersion was characterized by X-ray diffraction(XRD) amd differential scanning calorimeter(DCS). The improved bioavailability of solid dispersions was evaluated through in vivo pharmacokinetic studies. The optimum preparation process of meloxicam solid dispersion tablets was investigated, and the in vitro dissolution curve similarity factor f2 was used as the main evaluation index to screen and optimize the dosage of pH regulator, filler, disintegrator, lubricant, flow aid and the mixing time in the prescription. RESULTS The solid dispersion prepared with Kollidon@VA64 as carrier effectively maintained the supersaturated state of the drug in solution. The results of XRD and DSC showed that the crystal state of meloxicam in the solid dispersion was completely transformed into amorphous state. Compared with meloxicam, solid dispersions significantly increased the solubility, and its peak blood concentration(Cmax) and relative bioavailability were increased by 208.09% and 241.78%, respectively. The optimal formulation and process of meloxicam solid dispersion tablets prepared by direct powder pressing method were meloxicam solid dispersion 35.2%, lactose∶microcrystalline cellulose =1∶1.5, sodium citrate 9.8%, crosslinked povidone 8%, magnesium stearate 0.75%, silica 0.8%, and mixing time 5 min. The dissolution similarity factor f2 of the prepared meloxicam solid dispersion tablets and the original reference preparation in different pH medium was above 50. CONCLUSION Meloxicam solid dispersible tablets are prepared by hot melt extrusion and powder pressing method. The dissolution and bioavailability of meloxicam are improved, and the dissolution behavior of meloxicam is similar to that of the original reference preparation.

Objective To investigate the effects of 0.5 Gy 60Co γ-ray irradiation on intestinal tissue injury and intestinal microflora in mice.Methods C57BL/6N mice were irradiated with 0.5 Gy 60Co γ-ray at 1 d,3 d,7 d and 14 d after irradiation.Jejunum tissues were fixed and frozen,and feces were frozen.Hematoxylin-eosin staining was used to observe the pathological injury to jejunum after irradiation,ki67 immunohistochemical staining was adopted to detect the proliferation of jejunum crypt cells,and TdT-mediated dUTP nick end labeling was employed to detect the apoptosis of jejunum crypt cells.The expressions of TNF-α,IL-1β,IL-6 and IL-10 cytokines in small intestines were detected via radioimmunoassay.The changes of intestinal flora in mice after irradiation were analyzed by metagenomic sequencing,and LEfSe analysis and ROC analysis were used to screen the bacteria with significant differences.Results After 0.5 Gy 60Co γ-ray irradiation,the proliferative cells of the jejunal crypt were significantly decreased at 1 d after irradiation(P＜0.05),while the apoptotic cells were significantly increased at 1 and 3 d after irradiation(P＜0.01).The expression of TNF-α at 7 and 14 d after irradiation,that of IL-1 β at 1,3,7 and 14 d after irradiation and that of IL-6 at 3,7 and 14 d after irradiation were significantly increased(P＜0.05),while the expression of IL-10 at 7 and 14 d after irradiation was significantly decreased(P＜0.05).After 0.5 Gy 60Co γ-ray irradiation,intestinal flora composition changed significantly at phylum,genus and species levels,and Lactobacillus murinus,Lactobacillus johnsonii,Alistipes-unclassified,Mucispirillum schaedleri underwent the most significant changes and had higher LDA scores.Conclusion The whole body irradiation of 0.5 Gy 60Co γ-ray can cause intestinal tissue damage and change the composition of intestinal flora in mice.

Objective:To explore the clinical features of Heidenhain variant Creutzfeldt-Jakob disease (HvCJD) to deepen understanding and recognition of this disease.Methods:Clinical data of 1 case of HvCJD admitted to Hainan General Hospital on August 4, 2022, were collected, whose clinical characteristics were reviewed and analyzed, and literature review was conducted.Results:The 59 years old male patient initially experienced symptoms of blurred vision, followed by a rapid decline in cognitive function. Mini-Mental State Examination score was 21/30 and Montreal Cognitive Assessment score was 11/30. Diffusion-weighted magnetic resonance imaging demonstrated the presence of mild ribbon-like hyperintensity within the bilateral frontal-parietal-occipital-insular cortex. T 2WI fluid attenuated inversion recovery imaging exhibited slight hyperintensity within the bilateral parietal cortex. The electroencephalography showed atypical triphasic waves. The examination of cerebrospinal fluid demonstrated 14-3-3 protein with a positive result. Two months after onset of illness, follow-up revealed new symptoms of myoclonus in the patient. Finally, the patient was not effectively treated and died about 2.5 months after onset. Thirty-six relevant literatures of HvCJD were reviewed. Most Heidenhain variant patients exhibited occipital cortical diffusion weighted imaging hyperintensity. Posterior cortical damage may affect primary and higher-level visual processing, leading to various visual disturbances. The early symptoms were mainly visual symptoms, such as visual reduction, blurred vision, visual field defect and color vision impairment. Conclusions:HvCJD patients only present with various visual disorders at the onset, followed by other neurological symptoms. The disease progresses rapidly, and patients often die in a short period of time. The disease is very rare and is often misdiagnosed. Currently, there is no feasible and effective treatment for HvCJD.

Objective To observe the level of serum Meteorin-like protein(Metrnl)in patients with type 2diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD).To explore the predictive value of serum Metrnl for the occur-rence of NAFLD in T2DM patients.Methods From January 2022 to June 2023,218 patients with T2DM were initially diagnosed in the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University(Xuzhou First People's Hospital).According to whether NAFLD was combined,they were divided into T2DM group(n=105)and T2DM combined with NAFLD group(n=113).The general information,related biochemical and metabolic indicators of the two groups of patients were collected,and the serum Metrnl levels of the two groups were detected by enzyme-linked immunosorbent assay(ELISA).Results Homeostasis model assessment insulin resistance index(HO-MA-IR),glycosylated hemoglobin(HbA1c)and triglyceride(TG)in T2DM combined with NAFLD group were higher than those in T2DM group,while high-density lipoprotein cholesterol(HDL-C)and Metrnl were lower than those in T2DM group,and the differ-ences were statistically significant(P＜0.05).Logistic regression results showed that body mass index(BMI)and TG were risk factors for T2DM with NAFLD(OR＞1,P＜0.05),HDL-C and Metrnl were protective factors for T2DM with NAFLD(OR＜1,P＜0.05).Spearman correlation analysis showed that Metrnl was negatively correlated with TG,HbA1c,HOMA-IR and BMI in initially diagnosed T2DM patients(r＜0,P＜0.05),and positively correlated with HDL-C(r＞0,P＜0.05).Receiver operating characteristic(ROC)curve analysis show that,the area under the curve(AUC)of BMI,TG,HDL-C and Metrnl predicting T2DM combined with NAFLD was 0.719,0.701,0.736 and 0.771.The AUC of Metrnl was largest.Conclusion The serum Metrnl levels in initially diagnosed T2DM combined with NAFLD patients are lower than those in simple T2DM patients,and serum Metrnl levels has good predictive power for the presence of NAFLD in initially diagnosed T2DM patients.