Sepsis-induced lung injury is a common type of sepsis complicated with multiple organ dysfunction syndrome， whose uncontrolled inflammatory response and oxidative stress are the key pathological mechanisms. As an important pathway of anti-inflammatory and anti-oxidative stress， the nuclear factor-erythroid 2-related factor 2 （Nrf2） signaling pathway is very important in the occurrence and development of sepsis-induced lung injury. This review summarizes relevant research conducted over the past decade on the regulation of the Nrf2 signaling pathway by traditional Chinese medicine （TCM） to ameliorate sepsis- induced lung injury. It has been found that 14 kinds of TCM effective ingredients （including five types of compounds： flavonoids， terpenes， alkaloids， saponins， phenols） and 6 kinds of compound preparations （including three types of formulas： heat-clearing and detoxifying formulas， purgative formulas for promoting bowel movement， and formulas for reinforcing vital qi and consolidating the constitution） can inhibit inflammatory responses and oxidative stress by activating Nrf2 signaling pathway and intervening in related pathways such as those involving Kelch-like ECH-associated protein 1， heme oxygenase-1， antioxidant response element and AMP-activated protein kinase， thereby alleviating sepsis-induced lung injury.

Background Exposure to ozone (O₃) is closely associated with an increased risk of mortality in the population, but this association exhibits regional heterogeneity, and relevant research in northern and central-western China is limited. Hohhot, as a typical city in the northern and western region, has seen a significant upward trend in O₃ concentrations (an increase of 17.9 μg·m⁻³ in 2020 compared to 2016). Studies targeting this region can fill the regional research gap. Objective To evaluate the health effects of ground-level O₃ exposure on resident mortality in Hohhot from 2018 to 2023. Methods Air quality, meteorological, and mortality data in Hohhot from 2018 to 2023 were collected. A time-series analysis based on Quasi-Poisson generalized additive model (GAM) was employed, controlling for meteorological factors, day-of-week effects, and holiday effects, to assess the impact of O₃ on non-accidental mortality, mortality from circulatory system diseases (CSD), and mortality from respiratory system diseases (RSD). Results From 2018 to 2023, the non-accidental, CSD, and RSD mortalities in Hohhot amounted to 89721, 47394, and 11378 cases, respectively. The daily maximum 8-hour average O₃ concentration (O₃-8 h) was 90.00 μg·m⁻³. According to the Class I limit (100 μg·m⁻³) of GB 3095—2012 Ambient Air Quality Standard, the annual average number of days exceeding the standard was 144 d. For single-day lag effects, O₃ had the strongest health impact on non-accidental mortality and CSD mortality on the current day (lag0), with effect sizes of 0.78% (95%CI: 0.33%, 1.24%) and 1.10% (95%CI: 0.50%, 1.71%), respectively. The strongest impact on RSD mortality occurred on the second day (lag2), with an effect size of 1.61% (95%CI: 0.61%, 2.62%). The subgroup analyses showed that for every 10 μg·m⁻³ increase in O₃-8 h concentration, the risk of non-accidental mortality in females increased by 0.70% (95%CI: 0.01%, 1.41%); for CSD mortality, the risk in males and individuals aged ≥65 years increased by 0.73% (95%CI: 0.01%, 1.47%) and 0.76% (95%CI: 0.13%, 1.39%), respectively. During the warm season, statistically significant risks were observed for non-accidental, CSD, and RSD mortalities, with increases of 1.07% (95%CI: 0.54%, 1.60%), 1.31% (95%CI: 0.59%, 2.04%), and 2.27% (95%CI: 1.07%, 3.49%), respectively. In the two-pollutant models incorporating sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), particulate matter with an aerodynamic diameter of 10 micrometers or less (PM₁₀), and fine particulate matter (PM_2.5), the effect estimates (excess risk) of O₃ remained stable and statistically significant (P<0.05), indicating model robustness. Conclusion Ground-level O₃ exposure in Hohhot increases mortalities due to non-accidental causes, CSD, and RSD, with more pronounced effects during the warm season. Females and individuals aged ≥65 years may be susceptible populations. Therefore, relevant authorities should prioritize the potential health risks of O₃ exposure, particularly to vulnerable groups, and promote targeted prevention and control strategies.

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

With the development of the Scientific, Transparent and Applicable Rankings tool for clinical practice guidelines(STAR), the publication of evaluation and ranking for scientificity, transparency and applicability of Chinese guidelines and consensus published in the medical journals in 2021and 2022, as well as the publication of the STAR evaluation and ranking for some specialities, the STAR evaluation and ranking has received widespread attention in the medical community. In order to further enhance its scientificity and transparency, Methodology and Technology Specialization Committee of the STAR Working Group presents this article to introduce sample identification and speciality assignment in the evaluation and ranking process.

Objective To investigate the influencing factors for chronic pancreatitis(CP)complicated by pancreatogenic portal hypertension(PPH),and to establish a predictive model.Methods A retrospective analysis was performed for the clinical data of 99 patients with CP complicated by PPH who were hospitalized in The First Affiliated Hospital of Kunming Medical University,Chuxiong Yi Autonomous Prefecture People's Hospital,Wenshan People's Hospital,and Puer People's Hospital from January 2017 to December 2022,and these patients were enrolled as PPH group.The incidence density sampling method was used to select 198 CP patients from databases as control group.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups.The Least Absolute Shrinkage and Selection Operator(LASSO)regression model was used to identify the potential predictive factors for CP complicated by PPH,and the predictive factors obtained were included in the multivariate Logistic regression analysis to obtain independent risk factors,which were used to establish a nomogram prediction model.The receiver operating characteristic(ROC)curve,the calibration curve,and the Hosmer-Lemeshow goodness-of-fit test were used to perform internal validation of the model,and the clinical decision curve was used to assess the clinical practicability of the model.Results There were significant differences between the two groups in sex,history of recurrent acute pancreatitis attacks,acute exacerbation of CP,bile duct stones,peripancreatic fluid accumulation,pseudocysts,pulmonary infection,elevated C-reactive protein(CRP),elevated procalcitonin,fibrinogen(FIB),neutrophil-lymphocyte ratio(NLR),gamma-glutamyl transpeptidase,total bilirubin,direct bilirubin,low-density lipoprotein(LDL),serum amylase,D-dimer,and serum albumin(all P<0.05).The predictive variables obtained by the LASSO regression analysis included sex,recurrent acute pancreatitis attacks,bile duct stones,peripancreatic fluid accumulation,pulmonary infection,pseudocysts,CRP,NLR,FIB,and LDL.The multivariate Logistic regression analysis showed that sex(odds ratio[OR]=2.716,P<0.05),recurrent acute pancreatitis attacks(OR=2.138,P<0.05),peripancreatic fluid accumulation(OR=2.297,P<0.05),pseudocysts(OR=2.805,P<0.05),and FIB(OR=1.313,P<0.05)were independent risk factors for CP complicated by PPH.The above factors were fitted into the model,and the Bootstrap internal validation showed that the nomogram model had an area under the ROC curve of 0.787(95%confidence interval:0.730—0.844),and the calibration curve was close to the reference curve.The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good degree of fitting(χ2=7.469,P=0.487).The clinical decision curve analysis showed that the prediction model had good clinical practicability.Conclusion Male sex,recurrent acute pancreatitis attacks,peripancreatic fluid accumulation,pseudocysts,and FIB are independent risk factors for CP complicated by PPH,and the nomogram model established has good discriminatory ability,calibration,and clinical practicability.

Skin modeling of transdermal drug delivery system refers to experimental models that mimic the structure and function of human skin to explore and evaluate absorption,penetration,and efficacy of medicines in transdermal drug delivery.It provides an alternative to traditional human skin experiments and reduces the use of human skin in medical research,which is convenient,controllable,and cost effective.For skin models of transdermal drug delivery systems,this article introduces commonly used animal skin models,artificial skin models,and recombinant human skin models from the perspective of the transdermal absorption pathway of medicines,and analyzes their advantages,disadvantages,and applications so provide references the research and development of transdermal formulations and topical therapies.

Objective:To investigate the detection status and genotypes distribution characteristics of norovirus(NoV)in environmental sewage from three monitoring points in Fujian province, and to explore the significance of its application to NoV monitoring.Methods:Sewage samples were collected monthly at 5 sampling sites in representative monitoring cities, enriched and concentrated. Partial gene fragments of norovirus VP1 were amplified by reverse transcription-semi nested polymerase chain reaction (RT-snPCR), TA cloned and sequenced. Genotypes were identified based on the sequencing.Results:A total of 56 sewage samples were collected from July 2022 to June 2023. The detection rates of GⅠ and GⅡ were 89.29% (50/56) and 94.64% (53/56), respectively. A total of 7 NoV GⅠ genotypes and 13 GⅡgenotypes were identified. GⅠ.1, GⅠ.4, GⅡ.4 and GⅡ.17 were the dominant genotypes. NoV genotypes detected in different sampling sites were not exactly the same. The detection rate of NoV was low from August to November 2022, and the prevalence of the dominant genotypes was different in different seasons. GⅠ.1 and GⅡ.4 were highly prevalent from August to November 2022, but were replaced by GⅠ.4 and GⅡ.17 from December 2022 to June 2023, respectively. More NoV genotypes were detected in January-June 2023, comparing to the July-December 2022. The dominant genotype GII.17, has multiple clades and new variants have been discovered that are different from the 2014/2015 circulating strains.Conclusions:The detection rates of NoV in environmental sewage were very high, and genotypes were diverse. Environmental sewage surveillance could be an important complementary method for NoV cases surveillance.

Objective:To analyze the sensitivity of cytoplasmic light-chain immunofluorescence with fluorescence in situ hybridization in bone marrow smears (new FISH) for detecting cytogenetic abnormalities in multiple myeloma (MM) .Methods:42 MM patients admitted to the First Affiliated Hospital of Nanjing Medical University from April 2022 to October 2023 were enrolled. The patients with MM were detected by new FISH and CD138 immunomagnetic bead sorting technology combined with FISH (MACS-FISH) or cytoplasmic immunoglobulin FISH (cIg-FISH) to analyze cytogenetic detection results using combination probes which included 1q21/1p32, p53, IgH, IgH/FGFR3 [t (4;14) ], and IgH/MAF [t (14;16) ].Results:In 23 patients with MM, the abnormality detection rates of cIg-FISH and new FISH were 95.7% and 100.0%, respectively ( P>0.05). The detection rates of 1q21+, 1p32-, p53 deletion, and IgH abnormalities by cIg-FISH and new FISH were consistent, which were 52.2%, 8.7%, 17.4%, and 65.2%, respectively. The results of the two methods further performed with t (4;14) and t (14;16) in patients with IgH abnormalities were identical. The positive rate of t (4;14) was 26.7%, whereas t (14;16) was not detected. In 19 patients with MM, the abnormality detection rates of MACS-FISH and new FISH were 73.7% and 63.2%, respectively ( P>0.05). The positivity rate of 1q21+, 1p32- and IgH abnormalities detected by MACS-FISH were slightly higher than those detected by new FISH; however, the differences were not statistically significant (all P values >0.05) . Conclusion:The new FISH method has a higher detection rate of cytogenetic abnormalities in patients with MM and has good consistency with MACS-FISH and cIg-FISH.

Objective To investigate the effect and mechanism of ammonium pyrrolidine dithiocarbamate(PDTC)on neuroinflammatory injury in the penumbra of traumatic brain injury(TBI)in rats.Methods Sixty Sprague Dawley rats were divided into the PDTC group,TBI group,sham operation group and control group according to the random number table method,with 15 rats in each group.Rats in the PDTC group were intraperitoneally injected with PDTC(100 mg·kg-1)at 15 minutes before surgery;while the rats in the TBI group,sham operation group,and control group were intraperitoneally injected with the same volume of double distilled water.After the cranial window of rats in the TBI group and PDTC group was created,a 2.5 g steel rod with an inner diameter of 6.0 mm was dropped freely from a height of 75 cm through a transparent polyvinyl chloride tube with an inner diameter of 7.0 mm to impact the dura mater and induce right parietal lobe contusion and laceration to establish the TBI model;rats in the sham operation group were sealed with bone wax after the cranial window creation,without any impact applied;rats in the control group were raised under normal conditions.The modified neurological severity score(mNSS)was used to evaluate the degree of neurobehavioral damage in rats in each group at 1,4 and 7 days after modeling.At 2 days after modeling,5 rats in each group were decapitated,and brain tissues were taken for hematoxylin & eosin(HE)staining,and morphological changes of the brain tissues were observed under an optical microscope.The expressions of β-amyloid precursor protein(β-APP)and glial fibrillary acidic protein(GFAP)in the brain tissues of rats in each group were detected by immunohistochemical staining.At 24 hours after modeling,5 rats in each group were decapitated,and the right injured penumbra tissues were obtained;the expressions of nuclear transcription factor-κB(NF-κB)P65,phosphorylated NF-κB P65,inhibitor of NF-κB(IκB),phosphorylated IKB,NOD-like receptor protein 3(NLRP3)and caspase-1 protein in the right injured penumbra tissue of rats in each group were detected by Western blot,and the expressions of NF-κB P65,IκB,NLRP3 and caspase-1 mRNA in the right injured penumbra tissue of rats in each group were determined by real-time quantitative polymerase chain reaction.Results At 1,4,and 7 days after modeling,the mNSS scores of rats in the TBI group were signifi-cantly higher than those in the PDTC group,control group and sham operation group.The mNSS scores of rats in the PDTC group were significantly higher than those in the control group and sham operation group(P＜0.05);there was no statistically significant difference in mNSS scores between the sham operation group and the control group(P＞0.05).The neurons and neurogliocyte of rats in the control group and the sham operation group exhibited normal morphology,without swelling and wide-ning of intercellular space.Diffuse hemorrhagic changes were observed in the brain tissues of rats in the TBI group,with different morphologies of neuronal cell body,unclear cell membrane and cytoplasm,pyknosis of cell nuclei,often triangular shape,disappearance of normal structure and nucleoli,and diffuse white blood cells and red blood cells filling the field of vision.The lesion surrounding area of rats in the PDTC group showed ischemic changes,with mild shrinkage of neuronal volume,a uniform light red color,karyopyknosis,nuclear-cytoplasmic dissociation,disappearance of normal structure and nucleoli,and localization of neuroinflammation.There was no significant expression of β-APP and GFAP in the cerebral cortex of rats in the control group and the sham operation group,while the accumulation of β-APP and GFAP in neuronal serosae and/or axons was observed in the brain tissues of rats in the TBI group and the PDTC group.Compared with the TBI group,a decrease in the number and the expression intensity of β-APP and GFAP-positive stained neuronal cells in the cerebral cortex of rats was observed in the PDTC group.The relative expression of NF-κB P65 protein in the brain tissues of rats in the sham operation group,TBI group and PDTC group was significantly higher than that in the control group,and the relative expression of NF-κB P65 protein in the brain tissues of rats in the PDTC group was significantly higher than that in the TBI group(P＜0.05).The relative expression of phosphorylated NF-κB P65 protein in the brain tissues of rats in the PDTC group and the sham operation group was significantly lower than that in the control group,the relative expression of phosphorylated NF-κB P65 protein in the brain tissues of rats in the TBI group was significantly higher than that in the control group and the sham operation group,and the relative expression of phosphorylated NF-κB P65 protein in the brain tissues of rats in the PDTC group was significantly lower than that in both TBI group and sham operation group(P＜0.05).There was no significant difference in the relative expression of IκB protein in the brain tissues of rats between the sham operation group and the control group(P＞0.05);the relative expression of IκB protein in the brain tissues of rats in the TBI group was significantly higher than that in the control group,and the relative expression of IκB protein in the brain tissues of rats in the PDTC group was significantly lower than that in the control group,sham operation group,and TBI group(P＜0.05).The relative expression of phosphorylated IκB protein in the brain tissues of rats in the TBI group was significantly lower than that in the control group and the sham operation group,and the relative expression of phosphorylated IκB protein in the brain tissues of rats in the PDTC group was significantly higher than that in the TBI group(P＜0.05).The relative expression of NLRP3 protein in the brain tissues of rats in the sham opera-tion group was significantly higher than that in the control group,the relative expression of NLRP3 protein in the brain tissues of rats in the TBI group and the PDTC group was significantly lower than that in the sham operation group and the control group,and the relative expression of NLRP3 protein in the brain tissues of rats in the TBI group was significantly lower than that in the PDTC group(P＜0.05).The relative expression of caspase-1 protein in the brain tissues of rats in the sham opera-tion group,PDTC group,and TBI group was significantly higher than that in the control group,and the relative expression of caspase-1 protein in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P＜0.05).The relative expression of NF-κB P65 mRNA in the brain tissues of rats in the PDTC group,TBI group,and sham operation group was significantly higher than that in the control group,the relative expression of NF-κB P65 mRNA in the brain tissues of rats in the PDTC group and TBI group was significantly higher than that in the sham operation group,and the relative expres-sion of NF-κB P65 mRNA in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P＜0.05).The relative expression of IκB mRNA in the brain tissues of rats in the PDTC group and TBI group were signifi-cantly higher than that in the control group,and the expression of IκB mRNA in the brain tissues of rats in the sham operation group was significantly lower than that in the control group(P＜0.05).The relative expression of IκB mRNA in the brain tis-sues of rats in the PDTC group and TBI group was significantly higher than that in the sham operation group,and the relative expression of IκB mRNA in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P＜0.05).The relative expression of NLRP3 mRNA in the brain tissues of rats in the PDTC group and TBI group was significantly higher than that in the control group,the relative expression of NLRP3 mRNA in the brain tissues of rats in the sham operation group was significantly lower than that in the control group,the relative expression of NLRP3 mRNA in the brain tissues of rats in the PDTC group and TBI group was significantly higher than that in the sham operation group,and the relative expression of NLRP3 mRNA in the brain tissues of rats in the PDTC group was significantly lower than that in the TBI group(P＜0.05).The relative expression of caspase-1 mRNA in the brain tissues of rats in the sham operation group,TBI group,and PDTC group was significantly lower than that in the control group,the relative expression of caspase-1 mRNA in the brain tissues of rats in the TBI group and PDTC group was significantly higher than that in the sham operation group(P＜0.05).Conclusion PDTC can effectively improve neural functional deficit score and reduce neuroinflammatory injury in TBI rats,the mechanism of which may be related to regulating mRNA and protein expression of NF-κB/NLRP3 axis-related inflammatory injury indicators and regulating downstream inflammatory factors.