In 2022， Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%， a diagnostic rate of 90%， and a treatment rate of 80% among people aged 18 years and above by the year 2025， and the main intervention measures include population-based prevention， case screening， antiviral therapy， and health management. As of December 31， 2024， a total of 6.875 million individuals in the general population had been screened for hepatitis B， with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified， among whom 156 772 were diagnosed through serological reexamination， resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified， among whom 42 921 had hepatitis B-specific health records established for health management， with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy， with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened， among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing， resulting in a diagnostic rate of 79.2%， and 1 824 individuals with positive HCV RNA were identified， among whom 1 194 received antiviral therapy， with a treatment rate of 65.5%. In addition， 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis， a large number of hepatitis patients have been identified， treated， and managed in the province within a short period of time， which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.

Kounis syndrome is an acute coronary syndrome triggered by an allergic reaction, which is clinically rare and frequently subject to misdiagnosis or missed diagnosis. This article presents a case report of a 70-year-old male patient who developed a rash, pruritus, and chest pain following colon polyp resection. Coronary angiography revealed occlusion of the left anterior descending artery, and blood flow was restored after stent implantation. However, the patient experienced recurrent symptoms accompanied by loss of consciousness. Drug skin tests confirmed positive reactions to chlorhexidine and fondaparinux sodium, leading to a diagnosis of type Ⅱ Kounis syndrome. By avoiding allergenic drugs and combining antihistamines with symptomatic treatment to correct myocardial ischemia, the patient′s clinical symptoms significantly improved, and he eventually recovered and was discharged from the hospital. This case underscores the importance of maintaining vigilance for this syndrome in patients with allergies accompanied by chest pain and promptly identifying and avoiding allergens.

Stroke is the main cause of disability in adults.With the progress of stroke diagnosis and treatment technology,the mortality rate of stroke patients has decreased significantly,but its incidence keeps increasing,and there is an increasing number of stroke survivors develop chronic neurological disorders.At present,there is no clear drug to promote functional repair after stroke.Several studies have shown that gut microbiota can improve stroke prognosis by regulating neuroactive molecules and immune cell functions,enhancing neural network plasticity,and reducing neuroinflammation.Based on a review of previous studies,this paper describes the mechanism of action of gut microbiota on neural network plasticity and neuroinflammation after stroke and its impact on functional recovery after stroke and explores its clinical value and feasibility in improving neurological dysfunction after stroke.

Objective The purpose of this article is to summarize and review the current status of the construction of clinical research evaluation systems in domestic public hospitals,identify existing problems in the evaluation system,and propose development strategies and suggestions.Methods Retrieved relevant articles,dissertations and policies from the past five years(2018-2022),screened the titles,viewed the full texts of 52 selected papers and their references,and summarized them.Results The"five-only"indicators have long been an important indicator for evaluating clinical research in public hospitals,but in today's scientific research environment and policy environment,the"five-only"evaluation system has revealed its utilitarian draw-backs and gradually evolved into a hindrance to scientific research.It is urgent to break through the"five-only"orientation and establish a clinical research evaluation system oriented towards"transforming and applying transformation of scientific research achievements".Conclusion The evaluation system for clinical research should break the previous"five-only"evaluation model based on quantity-oriented scientific research evaluation.We can draw on the framework of the research output,influence,and environment indicators in the UK's REF Excellence Framework model,combine the American APT system and the Chinese STEM indicator dimensions,explore multi-outcome evaluation,integrate developmental indicators,and continuously improve the indica-tor system and application methods in practice to promote the development of clinical research in public hospitals.

Objective:To explore the distribution characteristics and antibiotic resistance of pathogen in children with hematological disorders and cancers complicated with sepsis in pediatric intensive care unit (PICU).Methods:The clinical data of children with hematological disorders and cancers complicated with sepsis hospitalized at Shenzhen Children′s Hospital affiliated to China Medical University from January 2016 to August 2023 were retrospectively analyzed. Patients were divided into survival group and death group based on the outcome of sepsis on 28 days after diagnosis.Results:A total of 202 sepsis episodes occurred in 176 children were enrolled in this study. Among all, 144 (71.3%) cases of bloodstream infection, 59 (29.2%) cases of pulmonary infection, 21 (10.4%) cases of abdominal infection, 9 (4.5%) cases of soft tissue infection, 9 (4.5%) cases of nervous system infection, and 3 (1.5%) cases of urinary tract infection. A total of 244 pathogenic strains were identified, in which 74 (30.3%) cases were gram-positive bacteria. The top 3 pathogens isolated were Coagulase negative Staphylococcus (21 strains), Staphylococcus aureus (19 strains) and Streptococcus pneumoniae (13 strains). Gram-negative bacteria accounted for 122 (50.0%) strains, in which top 3 were Klebsiella pneumonia (33 strains), Escherichia coli (25 strains), and Pseudomonas aeruginosa (23 strains). Fungi comprised 48 (19.7%) strains:the top 3 were Candida tropicalis (14 strains), Candida albicans (10 strains), Aspergillus and Pneumocystis jirovecii (7 strains each). The incidence of Acinetobacter baumannii, Stenotrophomonas maltophilia, and Pseudomonas aeruginosa were significantly higher in death group compared to survival group[9.0%（6/67）vs. 2.3%（4/177）, χ2＝3.971 ，P＝0.046; 9.0%（6/67）vs. 1.1%（2/177）, χ2＝7.080 ，P＝0.008;16.4%（11/67）vs. 6.8%（12/177）, χ2＝5.288 ，P＝0.021]. The samples of 57 cases were simultaneously detected by both culture and metagenomic next-generation sequencing (mNGS). Pathogens were detected in 25 cases by both culture and mNGS. In 30 cases, pathogen detection were mNGS positive but culture negative. Two cases showed positive results only with culture. A total of 79 (46.8%) strains were multi-drug resistant bacteria, including 27 (34.2%) strains of gram-positive bacteria and 52 (65.8%) strains of gram-negative bacteria. A total of 174 (86.1%) children with sepsis received empirical anti-infective drugs within 24 hours of fever onset. A total of 124 (61.4%) cases were appropriately covered by the initial empirical antibiotics, while 40 (19.8%) cases were not adequately covered and 10 (5.0%) cases had incomplete coverage. Despite the inclusion of pathogenic in the coverage, resistance to initial antibiotics was observed in 22 (10.9%) cases. Fifty-one patients died. Conclusion:The predominant pathogens responsible for sepsis in PICU with hematological disorders and cancers is gram-negative bacteria, followed by gram-positive bacteria and fungi. In comparison to healthy children with sepsis, there is a higher incidence of fungal infections among hematological disorders and cancers. The proportion of multi-drug resistant bacteria infection is high. Early identification and combination of local etiological distribution and drug resistance, along with the empirical selection of appropriate anti-infection treatment strategies, can greatly enhance survival rate.

Objective To investigate the effects of modified Yupingfeng Powder medicated serum on the inflammatory response of rat lung epithelial type Ⅱ cells RLE-6TN;To explore the mechanism based on nuclear factor(NF)-κB signaling pathway.Methods The inflammatory reaction of RLE-6TN cells was induced by lipopolysaccharide,and the cells were divided into control group,model group,dexamethasone medicated serum group,and 5%,10%and 20%TCM serum group,and the cell model was intervened with different serum.After 24 hours,the content of lactate dehydrogenase(LDH)in cell supernatant was detected by kit,and the content of reactive oxygen species(ROS)in cells were detected by fluorescence staining,Hoechst/PI double staining was used to observe cell apoptosis,and ELISA was used to detect tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and IL-1β contents in cell supernatant,RT-qPCR was used to detect Toll like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and NF-κB inhibitory protein α(IκBα)mRNA expression,Western blot was used to detect protein expressions of TLR4,MyD88,NF-κBp65 and IκBα.Results Compared with the control group,the contents of LDH,TNF-α,IL-6,IL-1β in RLE-6TN cell supernatant and ROS content in cells of model group significantly increased(P<0.01),the cell apoptosis rate significantly increased(P<0.01),the expressions of TLR4 and MyD88 mRNA and protein significantly increased(P<0.01),the expression of IκBα mRNA significantly decreased(P<0.01),and the ratio of p-NF-κBp65/NF-κBp65 and p-IκBα/IκBα significantly increased(P<0.01).Compared with the model group,the content of LDH,TNF-α,IL-6,IL-1 in RLE-6TN cell supernatant and ROS content in cells significant decreased in the 20%TCM serum group and dexamethasone medicated serum group(P<0.01),the cell apoptosis rate significantly decreased(P<0.01),the expressions of TLR4 and MyD88 mRNA and protein significantly decreased(P<0.05,P<0.01),the expression of IκBα mRNA significantly increased(P<0.01),and the ratio of p-NF-κBp65/NF-κBp65 and p-IκBα/IκBα significantly decreased(P<0.05,P<0.01).Conclusion Modified Yupingfeng Powder medicated serum can reduce RLE-6TN cells inflammatory reaction,and its mechanism may be related to the regulation of NF-κB signaling pathway.

BACKGROUND:Kidney deficiency is the main pathogenesis of osteoporosis.To study the relationship between the two major syndrome types of kidney deficiency,Kidney-Yang deficiency and Kidney-Yin deficiency,is beneficial for the development of clinical diagnosis and treatments based on the combination of disease and syndrome. OBJECTIVE:To evaluate the biomechanical differences of the rat femurs with Kidney-Yang deficiency and Kidney-Yin deficiency caused by Yougui pills,and to demonstrate the scientific efficacy of medication based on the combination of disease and syndrome in osteoporosis from a biomechanical perspective. METHODS:The bilateral ovaries of 60 female Sprague-Dawley rats were surgically removed to establish an ovariectomized osteoporosis model.At 10 weeks after modeling,all the rats were randomly divided into a Kidney-Yang deficiency group(n=30)and a Kidney-Yin deficiency group(n=30).Rats with Kidney-Yang deficiency were given gluteal intramuscular injection of hydrocortisone,while rats with Kidney-Yin deficiency were orally administered with thyroid tablet suspension,once a day,for 14 consecutive days.After successful modeling,20 rats in each group were given a suspension of Yougui pills by gavage once a day for 12 consecutive weeks and the remaining 10 rats were used as the control group without intervention.After gavage,the microstructural parameters of the bone were measured using Micro-CT scanning.Three-point bending,finite element simulation,femoral head compression,and surface indentation distribution experiments of the femurs were performed on a mechanical testing machine. RESULTS AND CONCLUSION:Micro-CT revealed that the femoral bone density,bone volume fraction,bone surface density,trabecular number,and trabecular separation were improved in the Kidney-Yin deficiency+Yougui pills group compared with the Kidney-Yin deficiency group(P＜0.05);the femoral bone volume fraction,bone surface density,trabecular number,and trabecular thickness were improved in the Kidney-Yang deficiency+Yougui pills group compared with the Kidney-Yang deficiency group(P＜0.05).The three-point bending experiment showed that the femur elastic modulus,maximum bending strength and bending fracture strength were decreased(P＜0.05)and toughness was increased(P＜0.05)in the Kidney-Yang deficiency+Yougui pills group compared with the Kidney-Yang deficiency group.Finite element simulation showed that Yougui pills could significantly improve the bending resistance of the femurs in the Kidney-Yang deficiency group,but had no significant effect on the Kidney-Yin deficiency group.The femoral head compression experiments showed that Yougui pills could enhance the ability of the femoral head to resist deformation in the Kidney-Yang deficiency group,but there was no significant difference in the effect of Yougui pills on the surface properties of the femoral head in the Kidney-Yin deficiency group and the Kidney-Yang deficiency group.To conclude,Yougui pills can significantly enhance the biomechanical properties of the osteoporotic bones with Kidney-Yang deficiency,but have no significant effect on the osteoporotic bone with Kidney-Yin deficiency.

ObjectiveTo investigate the effects of berbamine hydrochloride on sorafenib resistance in hepatocellular carcinoma cells and the underlying mechanisms. MethodThe sorafenib-resistant cell line SMMC-7721/S was selected by the concentration increment method starting at 1.25 μmol·L^-1 sorafenib. Both SMMC-7721 and SMMC-7721/S cells were treated with 0， 2.5， 5， 10， 15， 20 μmol·L^-1 sorafenib， and the cell counting kit-8 （CCK-8） assay was employed to determine the half maximal inhibitory concentration （IC₅₀） and calculate the resistance index （RI）. Western blot was conducted to compare the expression of proteins involved in autophagy and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway between SMMC-7721 and SMMC-7721/S cells. Furthermore， SMMC-7721/S cells were treated with 5 μmol·L^-1 berbamine hydrochloride alone or in combination with 2.5， 5， 10 μmol·L^-1 sorafenib， and the cell growth was assessed by the CCK-8 assay. In addition， SMMC-7721 and SMMC-7721/S cells were treated with 5 μmol·L^-1 berbamine hydrochloride alone or in combination with 5 μmol·L^-1 sorafenib， and the cell proliferation was examined by the colony formation assay. The immunofluorescence assays with Microtubule-associated protein 1 light chain 3 （LC3） and LysoTracker as probes were employed to assess the lysosomal acidification in SMMC-7721 cells treated with 5 μmol·L^-1 berbamine hydrochloride or 0.1 μmol·L^-1 autophagy inhibitor bafilomycin A1 （Baf）. Further， the expression of proteins involved in autophagy and PI3K/Akt/mTOR signaling pathway was determined by Western blot and compared between groups. ResultSorafenib showed the IC₅₀ of 9.56 mol·L^-1 （P<0.01） and 7.99 mol·L^-1 for SMMC-7721/S and SMMC-7721 cells， respectively， at 24 h. The resistance index （RI） of SMMC-7721/S for sorafenib was 1.20 （P<0.01）， which indicated mild resistance. Compared with SMMC-7721 cells， SMMC-7721/S cells exhibited up-regulated expression of p-mTOR， p-Akt， and LC3Ⅱ， down-regulated expression of p62 protein （P<0.01）， and unchanged Akt protein level. CCK-8 and colony formation assays demonstrated that the combination of berbamine hydrochloride and sorafenib exhibited a synergistic effect （Q>1.15）， with berbamine hydrochloride partially reversing the resistance of liver cancer cells to sorafenib. The immunofluorescence detection of LC3 revealed that berbamine hydrochloride and Baf significantly increased LC3 in SMMC-7721 cells. The detection with LysoTracker as the probe showed that berbamine hydrochloride inhibited the acidity of lysosomes in SMMC-7721 cells （P<0.01）， indicating the suppression of autophagy. Berbamine hydrochloride further enhanced the downregulation of p-mTOR and p-Akt protein levels and did not change the Akt protein level in SMMC-7721 cells exposed to sorafenib. Berbamine hydrochloride inhibited the increase in p-mTOR expression， down-regulated the p-Akt protein level， and did not change the total Akt protein level in the SMMC-7721/S cells exposed to sorafenib. ConclusionBerbamine hydrochloride can ameliorate the resistance of liver cancer cells to sorafenib by inhibiting cellular autophagy and the PI3K/Akt/mTOR signaling pathway.

Objective To explore the diagnostic value of serum neuronal Per-Arnt-Sim domain protein 4(NPASDP-4)and myelin basic protein(MBP)expression in patients with Parkinson's disease in relation to cognitive impairment(CI)and severity.Methods Selected and 138 Parkinson's disease patients admitted to the 909th Hospital of the Joint Logistics Support Force of the People's Liberation Army of China as the Parkinson's disease group,and 69 healthy people in the physical examination center of the hospital were in the healthy control group.Patients with Parkinson's disease were divided into normal cognitive function group(n=55),mild CI group(n=51)and dementia group(n=32)according to whether CI occurred and its severity.General data of subjects was collected,the serum levels of NPASDP-4 and MBP were detected by ELISA,correlation analysis was adopted by Spearman rank correlation or Pearson linear correlation,diagnostic value was analyzed by ROC curve,and influencing factors were analyzed by multivariate Logistic regression.Results Compared with the healthy control group,the levels of serum NPASDP-4(6.75±0.48 ng/ml vs 2.38±0.31 ng/ml)and MBP(8.34±0.65 μg/L vs 3.54±0.42 μg/L)in the Parkinson's disease group were increased with statistical significance(r=68.751,55.761,all P＜0.05).There were significant differences in H-Y stage among the normal cognitive function group,mild CI group and dementia group(x2=7.788,P＜0.05).Compared with the group with normal cognitive function(47.92±11.63 score),the mild CI group(50.78±13.69 score)and the dementia group(41.95±10.36 score)showed an increase in UPDRS-Ⅲ scores,and the differences were statistically significant(H=6.672,all P＜0.05).In normal cognitive function group,mild CI group and dementia group,the course of disease,and serum NPASDP-4(5.89±0.40,6.83±0.55,8.12±0.54 ng/ml)and MBP(6.65±0.56,8.94±0.69,10.27±0.70μg/L)levels were significantly increased(H=207.950,355.594,allP＜0.05),while MMSE score(28.47±0.94,24.51±1.35,17.09±2.57 score),MoCA score(27.45±1.03,20.18±1.92,11.75±2.53 score)and GPCOG total score(13.47±0.69,10.25±1.04,8.97±0.82 score)were significantly decreased,and the differences were statistically significant(H=515.005,775.933,327.584,all P＜0.05),respectively.The serum levels of NPASDP-4 and MBP in Parkinson's disease patients were significantly positively correlated with the course of disease(r=0.316,0.358),H-Y stage(r=0.345,0.384)and UPDRS-Ⅲ score(r=0.371,0.396),and significantly negatively correlated with MMSE score(r=-0.468,-0.517),MoCA score(r=-0.504,-0.569)and GPCOG total score(r=-0.527,-0.538)(all P＜0.05),respectivey.The areas under the curve(AUC)of the serum levels of NPASDP-4,MBP and their combination in diagnosing of Parkinson's disease were 0.850,0.930 and 0.960,respectively.The AUC of the serum levels of NPASDP-4 and MBP and their combination in diagnosing the severity of CI in patients with Parkinson's disease were 0.866,0.803 and 0.933,respectively.H-Y stage metaphase[OR(95％CI):4.725(1.742～12.814)],H-Y stage advanced[OR(95％CI):5.083(1.919～13.464)],UPDRS-Ⅲ score[OR(95％CI):3.257(1.464～7.246)],NPASDP-4[OR(95％CI):5.324(1.516～18.701)]and MBP[OR(95％CI):5.769(2.459～13.533)]were the influential factors for CI in patients with Parkinson's disease(all P＜0.05).NPASDP-4[OR(95％CI):4.768(2.382～9.543)]and MBP[OR(95％CI);5.846(3.141～10.882)]were the influential factors for the severity of CI in patients with Parkinson's disease(all P＜0.05).Conclusion The serum levels of NPASDP-4 and MBP in patients with Parkinson's disease were high,and they were closely related to CI and its severity,which may have certain clinical diagnostic value.

Objective:To investigate the effect of Fu-Fang-Yu-Jie(FFYJ)granules on LPS-induced inflammation model in bone marrow-derived macrophages(BMDM)and its intervention of FFYJ on nucleotide-bound oligomeric domain-like receptor protein 3(NLRP3)inflammatory signaling pathway in macrophages.Methods:Primary cells were extracted and isolated from the leg bone mar-row of C57BL/6 mice and BMDM macrophages were obtained after 7 days of induction with 50 ng/ml M-CSF.Groups included control group(Control),model group(LPS+ATP),FFYJ low dose group(FFYJ 50 μg/ml),FFYJ medium dose group(FFYJ 100 μg/ml),FFYJ high dose group(FFYJ 200 μg/ml)and positive drug dexamethasone group(DEX).BMDM in FFYJ treatment group and posi-tive drug group were pretreated for 1 hour before modeling.Lactate dehydrogenase(LDH)release assay was used to detect the level of LDH in the supernatant of each group of cells;ELISA was used to detect the level of inflammatory factors TNF-α,IL-6 and IL-1β in the supernatant of each group of cells;qRT-PCR was used to detect the levels of TNF-α,IL-6 and IL-1β in each group of cells;protein levels of NF-κB,p-NF-κB,NLRP3,Caspase-1 p45,Caspase-1 p20 and GSDMD-N in each group of cells were detected by Western blot;inverted fluorescence microscope was used to observe the cell pyroptosis of each group after Hoechst-PI staining.Results:Compared with control group,the levels of LDH,TNF-α,IL-6 and IL-1β in the supernatant of the model group were signifi-cantly higher(P<0.000 1);the mRNA levels of TNF-α,IL-6 and IL-1β in the model group were significantly higher(P<0.000 1);the protein levels of p-NF-κB,NLRP3,Caspase-1 p20 and GSDMD-N were significantly higher(P<0.05);and the number of PI-posi-tive cells was significantly higher(P<0.05).Compared with the model group,FFYJ and DEX significantly reduced the levels of LDH,TNF-α,IL-6 and IL-1β in the supernatant of BMDMs(P<0.05);down-regulated the mRNA levels of TNF-α,IL-6 and IL-1β in the cells(P<0.05);and inhibited the expressions of p-NF-κB,NLRP3,Caspase-1 p20 and GSDMD-N protein expressions(P<0.05);and significantly reduced the number of PI-positive cells(P<0.05).Conclusion:FFYJ exerts anti-inflammatory effects by inhibiting NLRP3 inflammasome activation in BMDM macrophages.