ObjectiveTo investigate the value of noninvasive imaging detection （FibroScan）， two serological models of gamma-glutamyl transpeptidase-to-platelet ratio （GPR） score and S index， and two inflammatory factors of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in predicting liver fibrosis in patients with HBeAg-positive chronic hepatitis B （CHB）， as well as the consistency of liver biopsy in pathological staging， and to provide early warning for early intervention of CHB. MethodsA retrospective analysis was performed for 131 HBeAg-positive CHB patients who underwent liver biopsy in The Third People’s Hospital of Kunming from January 2019 to December 2023. The results of liver biopsy were collected from all patients， and related examinations were performed before liver biopsy， including total bilirubin， alanine aminotransferase， platelet count， gamma-glutamyl transpeptidase， albumin， IL-6， TNF-α， liver stiffness measurement （LSM）， and abdominal ultrasound. An analysis of variance was used for comparison of normally distributed continuous data between groups， and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. A Kappa analysis was used to investigate the consistency between LSM noninvasive histological staging and pathological staging based on liver biopsy， and the Spearman analysis was used to investigate the correlation between each variable and FibroScan in the diagnosis of liver fibrosis stage. The Logistic regression analysis was used to construct joint predictive factors. The receiver operating characteristic （ROC） curve was used to evaluate the value of each indicator alone and the joint predictive model in the diagnosis of liver fibrosis， and the Delong test was used for comparison of the area under the ROC curve （AUC）. ResultsIn the consistency check， inflammation degree based on liver biopsy had a Kappa value of 0.807 （P<0.001）， and liver fibrosis degree based on liver biopsy had a Kappa value of 0.827 （P<0.001）， suggesting that FibroScan noninvasive histological staging and liver biopsy showed good consistency in assessing inflammation degree and liver fibrosis stage. Age was positively correlated with LSM， GPR score， S index， IL-6， and TNF-α （all P<0.05）， and GPR score， S index， IL-6， and TNF-α were positively correlated with LSM （all P<0.05）. GPR score， S index， IL-6， and TNF-α were all independent risk factors for diagnosing significant liver fibrosis （≥S2） and progressive liver fibrosis （≥S3） （all P<0.05）. As for each indicator alone， GPR score had the highest value in the diagnosis of significant liver fibrosis （≥S2）， followed by S index， IL-6， and TNF-α， while S index had the highest value in the diagnosis of progressive liver fibrosis （≥S3）， followed by GPR score， TNF-α， and IL-6. The joint model had a higher predictive value than each indicator alone （all P<0.05）. ConclusionThere is a good consistency between FibroScan noninvasive histological staging and pathological staging based on liver biopsy. GPR score， S index， IL-6， and TNF-α are independent risk factors for evaluating different degree of liver fibrosis in CHB， and the combined prediction model established by them can better diagnose liver fibrosis.

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

Objective To explore the influencing factors of spontaneous bacterial peritonitis in patients with primary liver cancer complicated with ascites and establish a prediction model.Methods A total of 292 patients with primary liver cancer complicated with ascites who were hospitalized for the first time in the Third People's Hospital of Kunming from January 2012 to December 2021 were selected as the study objects.General data,etiological indicators,serological indicators and complications of these subjects were collected.Then they were divided into the infection group(n = 114)and the control group(n = 178)according to whether spontaneous bacterial peritonitis(SBP)was complicated.Univariate and multivariate logistic regression were used to analyze the influencing factors of SBP in patients with primary liver cancer complicated with ascites.Finally,ROC curves were constructed to more intuitively represent the individual and combined predictive value of these targets.Results Am-ong 292 hepatocellular carcinoma patients with ascites,there were 235 males(80.48%)and 57 females(19.52%),among which 114 patients with SBP were in the infection group and 178 patients without SBP were in the control group.The results of univariate analysis showed that compared with the control group,the levels of WBC,neutrophils,prothrombin time,total bilirubin,albumin,CD3,CD4,CD8,CD4/CD8 ratio,CD19 procalcitonin,serum amyloid A,hypersensitive C-reactive protein,sodium,chlorine,alcohol consumption,shock,hepatorenal syndrome,hepatic encephalopathy,massive ascites in the infection group had statistically significant difference(P<0.05).Multi-factor analysis revealed that CD8,CD4/CD8 ratio were protective factors for SBP in patients with liver cancer ascites,CD19,procalcitonin,serum amyloid A,and massive ascites were risk factors for SBP in patients with ascites.ROC curve construction showed that serum amyloid A,CD8,CD4/CD8 ratio,CD19,procalcitonin,massive ascites area under curve(AUC)of massive ascites were 0.724,0.637,0.653,0.820,0.705,0.686,respectively.Conclusion CD8,CD4/CD8 ratio,CD19,procalcitonin,serum amyloid A,and a large volume of ascites are significant factors contributing to the development of spontaneous bacterial peritonitis(SBP)in patients with hepatocellular carcinoma ascites.The predictive value of combination is substantial,demonstrating a level of accuracy in forecasting SBP occurrence

Objective To establish a simultaneous detection approach for 34 emerging contaminants(ECs)in tap water by liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Human health risk assessment was performed according to the detection results from 43 tap water samples.Methods Tap water samples were concentrated and extracted by solid phase extraction,and then blown to near dry by nitrogen at 40℃.The sample extracts were dissolved in methanol-water solution(95:5,VN)to 0.5 mL for analyzing.Agilent Jet Stream Electrospray Ionization(AJS ESI)and the multiple reaction monitoring(MRM)mode were performed for MS to acquire the data of 34 ECs.A database including precursor ion,product ion and retention times was established accordingly.Results The average linear correlation coefficients(r)of 34 kinds of ECs was 0.995 9.The limits of detection were 0.01～0.60 ng/L and the recoveries were between 60.7％and 119.8％.The intra-group precisions were between 0.05％～9.89％and the intra-day precisions were between 0.20％～14.40％for the spiked samples.The method was applied to analyze 43 tap water samples and a total of 15 ECs were detected.According to the results,the detection rate of caffeine was the highest(84％),and the concentration range was ND～74.42 ng/L.Among all the ECs detected,1,2,3-benzotriazole had the highest concentration(ND～361.15 ng/L),where detection rate was 44％.Humans may be exposed to these ECs by drinking the tap water.The human health risk assessments of 12 kinds of ECs were carried out,however,the estimated risk was negligible(risk quotient＜0.01).Conclusion The method is simple,highly sensitive and selective,and could meet the detection needs of ECs at trace level in tap water.There was no human health risk posed for ECs identified in 43 tap water samples analyzed by this method.

Traumatic brain injury (TBI) can cause a series of secondary changes, such as neuronal dysfunction, blood-brain barrier destruction, secondary neurovascular injury, neuroinflammation, and even neurodegenerative diseases. In recent years, studies have found that microglia can regulate the long-term inflammation and tissue repair process after TBI through the changes of M1 phenotype and M2 phenotype, affecting the TBI progress. Therefore, this article reviews the recent advance in role of microglia, regulatory mechanisms and related therapies of microglia after TBI, in order to provide some references for TBI treatment.

Objective:To analyze the expression of circular RNA circ_0008274 in cetuximab-resistant colorectal cancer cells using bioinformatics technology and to explore its involvement in the development of cetuximab resistance.Methods:Five concentrations of cetuximab (10, 50, 100, 150, 200 nmol/L) were set. Cetuximab-resistant cells DiFi-R and Caco-2-R were screened out and established by concentration increasing method using colorectal cancer cells DiFi and Caco-2. The expression of circ_0008274 in DiFi-R and Caco-2-R cells was detected by reverse transcription-polymerase chain reaction(RT-PCR). The interaction and regulation between circ_0008274 and microRNA(miR)-140-3p were analyzed by double-luciferase reporter assay. The highly expressed gene SMARCC1 related to cetuximab resistance was determined by Western blotting. Circ_0008274 in DiFi-R and Caco-2-R cells were knocked out with small interfering RNA si-circ_0008274 transfection. After knock out, the differences in the colony formation and cell proliferation in DiFi-R and Caco-2-R cells were compared. MiR-140-3p mimic and blank control miR were transfected into DiFi-R and Caco-2-R cells. After transfection the difference in cell proliferation between transfected with miR-140-3p mimic and blank control miR in DiFi-R and Caco-2-R cells were analyzed. After Caco-2-R cell was knocked out with si-circ_0008274, the changes of SMARCC1 protein expression rescued by pcDNA3.1 SMARCC1 and cell viability were analyzed. The tumor specimens of 15 colorectal cancer patients hospitalized in Renmin Hospital of Wuhan University from March 2019 to August 2020 were included. According to the treatment effect, the patients were divided into sensitive group (11 cases) and drug-resistant group (4 cases). The relative expression levels of circ_0008274, downstream SMARCC1and miR-140-3p in colorectal cancer tissues in the two groups were detected by RT-PCR. Independent sample t test was used for statistical analysis. Results:The level of circ_0008274 in DiFi-R cells was 2.33±0.12 times of that of DiFi cells, while the level in Caco-2-R was (2.92±0.42) times of that of Caco-2 cells, and the differences were statistically significant ( t=19.97 and 7.80, both P<0.05). The results of double-luciferase reporter showed that after miR-140-3p mimic combined with wild-type circ_0008274, the relative fluorescence intensity was lower than before (0.28±0.04 vs. 1.00±0.00), and the difference was statistically significant ( t=-30.71, P=0.001). The expression of SMARCC1 protein in DiFi-R and Caco-2-R cells was significantly increased, the expression at protein level was higher than that of DiFi and Caco-2 cells (2.22±0.36 vs. 0.61±0.17, 0.85±0.11 vs. 0.35±0.08), and the differences were statistically significant ( t=6.23 and 6.32, both P<0.01). After circ_0008274 was knocked out, the numbers of colony formation of DiFi-R and Caco-2-R cells were both lower than those of before knockout (36.67±4.04 vs. 66.00±9.54, 17.35±4.04 vs. 52.33±8.02), the relative active cell ratios after interventing by 10, 50, 100, 150 and 200 nmol/L cetuximab were also lower than those of before knockout (DiFi-R cells: (73.75±2.75)% vs. (88.10±2.48)%, (56.50±6.66)% vs. (75.15±6.03)%, (35.75±5.32)% vs. (59.63±6.67)%, (24.25±3.30)% vs. (52.40±6.71)%, (6.25±2.75)% vs. (48.60±5.38)%; Caco-2-R cells: (63.74±5.25)% vs. (85.76±4.79)%, (56.50±4.20)% vs.(83.50±3.90)%, (46.00±2.94)% vs. (80.00±6.05)%, (35.30±5.56)% vs. (68.30±4.57)%, (12.25±7.37)% vs. (62.40±7.51)%), and the differences were statistically significant ( t=4.90, 6.71, -7.75, -4.16, -5.60, -7.53, -14.02, -6.19, -8.33, -10.10, -9.17 and -9.56, all P<0.01). After transfecting with miR-140-3p mimic, the relative active cell ratios of DiFi-R and Caco-2-R cells interventing by 10, 50, 100, 150 and 200 nmol/L cetuximab were both lower than those transfected with blank control miR (DiFi-R cells: (71.55±4.97)% vs. (85.90±2.66)%, (51.58±3.91)% vs. (74.95±6.35)%, (41.23±8.84)% vs. (58.43±7.05)%, (28.60±5.26)% vs. (53.75±5.65)%, (18.90±5.13)% vs. (51.30±3.30)%; Caco-2-R cells: (61.75±2.22)% vs. (90.10±1.41)%, (53.25±4.17)% vs. (86.18±2.69)%, (46.38±4.55)% vs. (77.75±6.70)%, (36.10±8.76)% vs. (70.15±4.18)%, (24.25±2.63)% vs. (65.10±7.62)%), and the differences were statistically significant ( t=-5.09, -6.47, -3.05, -6.28, -10.30, -21.48, -12.83, -8.01, -6.79 and -10.12, all P<0.01). After circ_0008274 was knocked out, the SMARCC1 protein level of Caco-2-R cells rescued by pcDNA3.1 SMARCC1 was higher than that of before rescue (0.63±0.19 vs. 0.09±0.03), and the relative active cell ratios after interventing by 10, 50, 100, 150 and 200 nmol/L cetuximab were also higher than that of before rescue ((93.10±3.56)% vs. (83.83±3.97)%, (83.28±4.26)% vs. (60.90±7.02)%, (61.83±2.12)% vs. (50.10±5.59)%, (53.20±3.74)% vs. (40.50±3.42)%, (46.20±4.08)% vs. (30.80±4.82)%), and the differences were statistically significant( t=3.55, 3.52, 5.44, 3.87, 4.64 and 4.88, all P<0.01). The relative expression levels of circ_0008274 and downstream SMARCC1 of colon cancer tissues in the drug-resistant group were higher than those in the sensitive group (6.45±1.32 vs. 2.26±1.39, 12.53±1.60 vs. 3.82±1.56), and the relative expression level of miR-140-3p was lower than that in the sensitive group (3.91±1.25 vs. 7.43±2.23), and the differences were statistically significant ( t=5.22, 9.51, -2.93, all P<0.01). Conclusions:Circular RNA circ_0008274 is highly expressed in colorectal cancer tissues and cetuximab resistant cells, interacts and inhibits miR-140-3p expression, up-regulates SMARCC1, and participates in the occurrence of cetuximab resistance. PcDNA3.1 SMARCC1 rescue can block the sensitization effect of si-circ_0008274 on cetuximab, and can significantly increase cetuximab resistance of colorectal cancer cells.

Autoimmune or infectious diseases often instigate the undesirable damages to tissues or organs to trigger immune-related diseases, which involve plenty of immune cells, pathogens and autoantibodies. Nanomedicine has a great potential in modulating immune system. Particularly, biomimetic nanomodulators can be designed for prevention, diagnosis and therapy to achieve a better targeted immunotherapy. With the development of materials science and bioengineering, a wide range of membrane-coated nanomodulators are available. Herein, we summarize recent advancements of bioinspired membrane-coated nanoplatform for systemic protection against immune-related diseases including autoimmune and infectious diseases. We also rethink the challenges or limitations in the progress of the therapeutic nanoplatform, and discuss the further application of the nanomodulators in the view of translational medicine for combating immune-related diseases.

Objective To investigate the current status of healthcare-associated infection (HAI),community-associated infection(CAD,and antimierobial use in hospitalized patients in medical institutions of Guizhou Province.Methods In September 2014,infection status of hospitalized patients in 174 second level hospitals and above in Guizhou Province were performed cross-sectional survey.Results A total of 68 419 patients were surveyed,the actual survey rate was 99.65％.1 581 patients developed 1 684 cases of HAI,HAI prevalence rate and HAI case prevalence rate were 2.31％ and 2.46％ respectively,18 571 patients developed 19 191 cases of HAI,CAI prevalence rate and CAI case prevalence rate were 27.14％ and 28.05％ respectively;patients in general intensive care unit(ICU) and pediatric department(non-neonatal group) had the highest HAI and CAI prevalence rates respectively.Constituent ratios of HAI and CAI sites was significantly different(x2 =17 325.44,P＜0.01);Escherichia coli was the main pathogen causing HAI and CAI.Utilization rate of antimicrobial agents on the survey day was 39.82 ％,ICU (80.47 ％) and pediatric department (76.67 ％) were the highest.Therapeutic antimicrobial use accounted for 67.48 ％ (n =18 386),single antimicrobial use accounted for 79.55 ％ (n =21 672).Pathogenic detection rate of specimens from patients receiving therapeutic antimicrobial agents was 31.76％.Conclusion This survey is helpful for understanding the high risk departments and sites of HAI and CAI in Guizhou Province,as well as pathogenic detection rate of specimens from patients receiving therapeutic antimicrobial agents,which provides basis for further prevention and control of HAI.

Objective To investigate the diagnostic value of serum LP ( a) and C-reactive protein ( CRP) in patients with ca-rotid atherosclerosis vulnerable plaque .Methods One hundred and twenty-eight patients with acute cerebral infarction coupled with carotid atherosclerosis were selected for the study , and they were divided into the vulnerable plaque group (90 cases) and the stable plaque group(38 cases) in accordance with the detection results from color Doppler ultrasonorgraphy .Then, the levels of LP(a) and CRP in the two groups were measured .Results The levels of LP(a) and CRP in the vulnerable plaque group were significantly higher than those in the stable plaque group , and statistical significance could be seen , when comparisons were made between the 2 groups ( P<0.01).Conclusion The higher levels of LP(a) and CRP might indicate that there was probably a transfer from the stable plaque to the vulnerable plaque .

Objective To explore the status of healthcare-associated infection(HAI)in hospitals in Buyi autono-mous prefecture of Guizhou Povince,and provide basis for formulating HAI control measures.Methods A survey was conducted by combined methods of bed-side survey and medical record reviewing,prevalence rates of secondary and above hospitals in Buyi autonomous prefecture in Guizhou Province between September 10 and October 5,2014 were surveyed.Results 6 577 hospitalized patients should be investigated,6 541(99.45%)were actually investiga-ted.The prevalence rate and case prevalence rate of HAI were 1 .83% (n=120)and 1 .94%(n=127)respectively. The top three departments of HAI distribution were intensive care unit (26.32%),neurosurgery (6.10%),and neonatal intensive care unit(5.13%);the main infection site was lower respiratory tract(n=39,30.71 %),followed by skin-soft tissue (n=24,18.90%)and superficial incision (n=23,18.11 %).58 pathogenic isolates were detec-ted,gram-negative bacteria were the major pathogens (n=44),gram-positive bacteria and fungi were 10 and 3 iso-lates respectively.Antimicrobial usage rate at survey day was 42.12%,64.75% of which were for therapeutic, 26.83% for prophylactic,and 8.42% for therapeutic+prophylactic use;the percentage of mono-drug,two drugs combination,and three or more drugs combination use were 79.53%,19.89%,and 0.58% respectively;bacterial detection rate in patients receiving therapeutic as well as therapeutic+prophylactic antimicrobial use was 13.76%. Conclusion Survey on prevalence of HAI is helpful for understanding the current status of HAI,monitoring on HAI in key departments of hospital and key sites of patients should be strengthened to reduce the occurrence HAI effectively.