ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked （DDX3X） in immune-mediated liver injury （ILI）， and to clarify its mechanism by regulating endoplasmic reticulum stress （ERS）-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A （ConA） via the caudal vein to establish a model of ILI， PBS （control group） and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice （DDX3X^ΔHep and DDX3X-flox mice （DDX3X^fl/fl）， respectively.. The log-rank survival analysis， measurement of the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）， and HE staining of liver tissue were performed to assess liver injury， and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid （4-PBA， 100 mg/kg） was performed to inhibit ERS. Serum samples （n=30） and liver tissue samples （n=6） were collected from healthy controls， chronic hepatitis B （CHB） patients， and hepatitis B virus-associated liver failure （HBV-LF） patients； ELISA was used to measure the serum level of DDX3X， and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice， the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury （P<0.05）， and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% （compared with 20% in the DDX3X^fl/fl group）， with significant reductions in the serum levels of ALT and AST （P<0.000 1） and the expression levels of the ERS markers GRP78 and CHOP （P<0.05）. After ERS was inhibited by 4-PBA， there was alleviation of liver injury （with reductions in ALT and AST， P <0.001） and a reduction in DDX3X expression （P<0.01）. The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls （all P<0.01）， and there was a significant increase in the serum level of DDX3X in HBV-LF patients （P<0.000 1）. ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway （GRP78/CHOP）， and its expression is associated with the progression of hepatitis B. Therefore， it can be used as a potential therapeutic target.

ObjectiveTo investigate the effects of Scutellariae Radix combined with epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） on cell proliferation， apoptosis， cancer stem cell （CSC） marker expression， and metabolism in non-small cell lung cancer （NSCLC） cells. MethodsThe anti-tumor effects of Scutellariae Radix and EGFR-TKIs （gefitinib or osimertinib） in NSCLC cells were evaluated using the cell counting kit-8 （CCK-8） and Annexin V-FITC/propidium iodide （PI） double staining apoptosis assay. The activity of Scutellariae Radix and EGFR-TKIs in three-dimensional （3D） cultures of NSCLC cells was assessed using the CellTiter-Glo® 3D cell viability assay. The mRNA and protein expression levels of CSC markers， sex determining region y box protein 2 （SOX2） and aldehyde dehydrogenase 1 family member A1 （ALDH1A1）， were detected by quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot， respectively. Changes in intracellular reactive oxygen species （ROS） levels were detected by ROS staining， and the redox ratio was detected by femtosecond laser labeling free imaging （FLI）. ResultsUnder both two-dimensional （2D） and 3D culture conditions， compared with the blank group and EGFR-TKI group， the combination group showed significantly reduced cell viability and increased apoptosis rate （P<0.05）. Compared with the EGFR-TKI group， the mRNA and protein levels of CSC markers were significantly downregulated in the combination group （P<0.05）. Additionally， the redox ratio was significantly elevated （P<0.05）， and ROS levels were also increased in the combination group compared with the EGFR-TKI group. ConclusionIn NSCLC cells， Scutellariae Radix enhances the redox ratio and increases ROS levels， thereby inhibiting the expression of CSC markers and strengthening the anti-tumor effects of EGFR-TKIs. This provides a novel molecular mechanism by which Scutellariae Radix may enhance the sensitivity of targeted therapies.

Objective:To evaluate the safety and efficacy of belimumab(BLM) in patients with SLE.Methods:Clinical data were collected for SLE patients who were diagnosed and treated with BLM in the Department of Rheumatology and Immunology (inpatient and outpatient department) of Guilin Medical College Affiliated Hospital from 1 December, 2019 to 12 May, 2023. BLM + standard of care (SOC) for the BLM group and SOC only for the SOC group. The primary clinical endpoint was adverse events (AE) occurring in groups, and the secondary clinical endpoint was disease activity index including SLEDAI-2000, clinical indicators, glucocortoid dosage reduction, and disease flare in the two groups. Propensity score matching method, independent sample t-test, non-parametric rank-sum test, variance analysis were used for statistical analysis. Results:Among the 79 BLM patients included, 48 had hematological impairment (61%), 53 had renal impairment (67%), 11 had skin and mucosal impairment (14%), 20 had joint impairment (25%), and 2 had neurological impairment(3%). There were no serious adverse events during the treatment in both groups. In the BLM group, with 14 cases experienced respiratory system infection, 1 with urinary system infection, 3 with skin infection, 4 with herpes virus infection, and 16 with liver function impairment. In the SOC group, there were 26 cases experienced respiratory system infection, 1 with urinary system infection, 6 with digestive system symptoms, 6 with skin infection, 4 with herpes virus infection, 10 with liver function impairment, 2 with thrombosis, and 1 with sepsis. Patients tolerated BLM generally well, with fewer adverse events occurring [in patients with the long course treatment, the number of AE cases in the BLM group vs SOC group 11 [(33%) vs 22 (68%), ( χ2=3.74, P=0.053)]. From all study groups and high-dose glucocorticoid (≥20 mg) groups, it was observed that the BLM group had a more significant reduction in glucocortoid dose [baseline glocucorticoid reduction in the BLM group decreased from 20 (12, 40)mg/d to 6 (4, 10)mg/d ( Z=0.12, P=0.01). In the renal injury group, after treatment, serum creatinine level decreased in the BLM group glomerular filtration rate increased from 72.37 (41.97, 95.74) to 97.03 (71.18, 114.34) ( Z=-4.62, P<0.001). There was less flares in the BLM group [7 cases (28%) vs 18 cases (72%), χ2=5.58, P=0.018] when compared with the soc group. Conclusion:BLM is safe and effective for the treatment of SLE, which can reduce disease activity, improve clinical parameters, reduce glocucorticoid dosage, and have a low flare rate.

Objective:To evaluate the auxiliary diagnosis value of bacterial culture, polymerase chain reaction (PCR) and serum anti-pertussis toxin immunoglobulin G (AntiPT-IgG) level detection in suspected pertussis.Methods:A total of 110 suspected cases of pertussis treated in the Department of Pediatrics of Wuhu No.1 People′s Hospital from June 2018 to May 2019 were recruited for the study.The nasopharyngeal swabs of all cases were collected for Bordetella pertussis culture and specific nucleic acid PCR detection.Serum samples of 78 cases were collected for the detection of AntiPT-IgG level by enzyme linked immunosorbent assays.Results:The positive rates of bacterial culture group and PCR group were 21.8% and 30.0%, respectively, with no statistically significant difference ( χ2=1.198, P>0.05). The culture positive rate of cases with the duration of cough<2 weeks was 32.1%, which was signi-ficantly higher than that of cases with the duration of cough about 2-4 weeks (14.3%) or >4 weeks (9.1%) ( χ2=6.522, P<0.05). The PCR positive rate of cases with the duration of cough <2 weeks was 39.6%, which was also significantly higher than that of cases with the duration of cough about 2-4 weeks (25.7%) or > 4 weeks (13.6%) ( χ2=6.126, P<0.05). The mean value for serum AntiPT-IgG level of 78 cases was (75.727±78.454) IU/mL, the median AntiPT-IgG levels of cases with the duration of cough<2 weeks and about 2-4 weeks were 5.909 IU/mL and 20.948 IU/mL, respectively, and the positive rates were 14.7% and 38.1%, respectively.The AntiPT-IgG level of cases with the duration of cough> 4 weeks and that at convalescent stage were (79.281±68.254) IU/mL and (107.242±75.750) IU/mL, and the positive rates were 39.1% and 57.1%, respectively. Conclusions:In the vaccine era, the results of pathogenic and serological tests should be combined to assist the clinical diagnosis of pertussis.The positive rate of bacterial culture and specific nucleic acid pathogen detection in children with cough duration less than 2 weeks is high, and the serological diagnosis is more effective after the duration of cough is over 4 weeks.

Objective To study miRNA expression differences in ovalbumin(OVA)- induced murine asthma models of mice and mast cells stimulated by inflammatory cytokines stimulation,and to better understand asthma deve-lopment so as to provide potential target for its prevention and treatment. Methods OVA - induced murine asthma models were validated by detecting cells in bronchoalveolar lavage fluid(BALF)and histopathology. And miRNA ex-pression differences in the lung tissues between the model group and the normal control group were detected by real -time polymerose chain reaction PCR . After tumor necrosis factor - α(TNF - α),interleukin 12(IL - 12)stimulation, miRNA expression differences in murine mast cells P815 were detected. Results The number of total cells and eosino-phil cells both increased in BALF of the model group[(12. 8 ± 2. 2)x 107 / L vs(5. 6 ± 2. 5)x 107 / L,t = 4. 760,P ﹤0. 05;(6. 6 ± 1. 9)x 107 / L vs(0. 8 ± 0. 8)x 107 / L,t = 8. 068,P ﹤ 0. 05]. In addition,histopathology showed more inflammatory cell infiltration in the model group than that in the normal control group,indicating that the models were validated. The expression of miRNA - 155 was up - regulated approximately 5. 0 - fold in the lung tissues of the model group(P ﹤ 0. 05),while miRNA - 192 showed no differences compared with the controls. After TNF - α and IL - 12 stimulated P815 mast cells,miRNA - 192 expressions in P815 were expression in P815 was up - regulated approximate-ly 1. 9 - fold and 1. 7 - fold after TNF - α and IL - 12 stimulation,respectively(P ﹤ 0. 05). Conclusions It is conclu-ded that miRNAs are differentially expressed in the presence of OVA - induced murint asthma models and mast cells stimulated by inflammatory cytokines. These differentially expressed miRNAs may regulate the function of mast cells and involved in the pathogenesis of asthma.