ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

[Objective] To conduct a retrospective statistical comparison of alanine aminotransferase (ALT) test values in blood donors prior to blood collection, aiming to analyze the objective characteristics of the population with elevated ALT levels (ALT>50 U/L) and provide reference data for adjusting the screening eligibility threshold for ALT. [Methods] The preliminary ALT screening data of 30 341 blood donor samples collected prior to blood donation from three smart blood donation sites at the Shenzhen Blood Center between 2022 and 2023 were extracted and compared with data from a health examination department of a tertiary hospital in Shenzhen (representing the general population, n=24 906). Both datasets were categorized and statistically described. A retrospective analysis was conducted to examine the associations between ALT test results and factors such as donors' gender, age, ethnicity, donation site, donation season, and frequency of blood donation. [Results] The ALT levels in both blood donors and the general population were non-normally distributed. The 95th percentile of ALT values was calculated as 61.4 U/L (male: 67.8 U/L, female: 39.3 U/L) for blood donors and 58.1 U/L (male: 63.7 U/L, female: 51.2 U/L) for the general population. The non-compliance rates (ALT>50 U/L) were 7.65% (2 321/30 341) in blood donors and 7.08% (1 763/24 906) in the general population. There were significant differences (P<0.05) in the ALT failure rate among blood donors based on gender, age, and donation site, but no significant differences (P>0.05) during the blood donation season. There was no statistically significant difference (P>0.05) in the positive rates of four serological markers (HBsAg, anti HCV, HIV Ag/Ab, anti TP) for blood screening pathogens between ALT unqualified and qualified individuals (2.05% vs 1.5%). If the ALT qualification threshold was raised from 50 U/L to 90 U/L, the non qualification rates of male and female blood donors would decrease from 9.82% (2 074/21 125) to 2.23% (471/21 125) and from 2.70% (249/9 216) to 0.75% (69/9 216), respectively. Among the 154 blood donors who donated blood more than 3 times, 88.31% of the 248 ALT test results were in the range of 50-90 U/L. Among them, 9 cases had ALT>130 U/L, and ALT was converted to qualified in subsequent blood donations. [Conclusion] There are differences in the ALT failure rate among blood donors of different genders and ages, and different blood donation sites and operators can also affect the ALT detection values of blood donors. The vast majority of blood donors with ALT failure are caused by transient and non pathological factors. With the widespread use of blood virus nucleic acid testing, appropriately increasing the ALT qualification threshold for blood donors can expand the qualified population and alleviate the shortage of blood sources, and the risk of blood safety will not increase.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Aim To establish NCI-H446/EP for small cell lung cancer resistant cells resistant to cisplatin and etoposide, and to evaluate their biological characteristics and multidrug resistance. Methods Nude mice were subcutaneously inoculated with NCI-H446 cells of SCLC to construct an in vivo model of xenograft tumor, and were given first-line EP regimen treatment for SCLC, inducing drug resistance in vivo, and stripping tumor tissue in vitro culture to obtain drug-resistant cells. The resistance coefficient, cell doubling time, cell cycle distribution, expression of multidrug resistance gene (MDR1), and drug resistance-related protein were detected in vitro, and the drug resistance to cisplatin and etoposide in vivo were verified. Results Mice with NCI-H446 tumors acquired resistance after eight weeks' EP regimen treatment, and the drug-resistant cell line NCI-H446/EP was obtained by isolation and culture in vitro. The resistance factors of this cell line to cisplatin, etoposide, SN38 and doxorubicin were 12.01, 18.36, 65.4 and 10.12, respectively. Compared with parental cells, the proportion of NCIH446/EP cells in Q

Manganese superoxide dismutase catalyzes the dismutation of two molecules of superoxide radicals to one molecule of oxygen and one molecule of hydrogen peroxide. The oxidation of superoxide anion to oxygen by Mn³⁺SOD proceeds at a rate close to diffusion. The reduction of superoxide anion to hydrogen peroxide by Mn²⁺SOD can be progressed parallelly in either a fast or a slow cycle pathway. In the slow cycle pathway, Mn²⁺SOD forms a product inhibitory complex with superoxide anion, which is protonated and then slowly releases hydrogen peroxide out. In the fast cycle pathway, superoxide anion is directly converted into product hydrogen peroxide by Mn²⁺SOD, which facilitates the revival and turnover of the enzyme. We proposed for the first time that temperature is a key factor that regulates MnSOD into the slow- or fast-cycle catalytic pathway. Normally, the Mn²⁺ rest in the pent-coordinated state with four amino acid residues (His26, His74, His163 and Asp159) and one water (WAT1) in the active center of MnSOD. The sixth coordinate position on Mn (orange arrow) is open for water (WAT2, green) or O₂^• to coordinate. With the cold contraction in the active site as temperature decreases, WAT2 is closer to Mn, which may spatially interfere with the entrance of O₂^• into the inner sphere, and avoid O₂^•/Mn²⁺ coordination to reduce product inhibition. Low temperature compels the reaction into the faster outer sphere pathway, resulting in a higher gating ratio for the fast-cycle pathway. As the temperature increases in the physiological temperature range, the slow cycle becomes the mainstream of the whole catalytic reaction, so the increasing temperature in the physiological range inhibits the activity of the enzyme. The biphasic enzymatic kinetic properties of manganese superoxide dismutase can be rationalized by a temperature-dependent coordination model of the conserved active center of the enzyme. When the temperature decreases, a water molecule (or OH^-) is close to or even coordinates Mn, which can interfere with the formation of product inhibition. So, the enzymatic reaction occurs mainly in the fast cycle pathway at a lower temperature. Finally, we describe the several chemical modifications of the enzyme, indicating that manganese superoxide dismutase can be rapidly regulated in many patterns (allosteric regulation and chemical modification). These regulatory modulations can rapidly and directly change the activation of the enzyme, and then regulate the balance and fluxes of superoxide anion and hydrogen peroxide in cells. We try to provide a new theory to reveal the physiological role of manganese superoxide dismutase and reactive oxygen species.

Objective:To compare the effects of invisible orthodontic appliances without brackets and labial fixed orthodontic appliances on periodontal status and root resorption in orthodontic patients.Methods:A retrospective study was conducted on 102 orthodontic patients who visited the Affiliated Hospital of Jining Medical University from January 2019 to October 2022. According to different treatment methods, they were divided into group A ( n=52) and group B ( n=50). Group A was treated with invisible orthodontic appliances without brackets, while group B was treated with labial fixed orthodontic appliances. We compared two groups of treatment completion time, root resorption, and periodontal health indicators before and after treatment, including plaque index (PLI), gingival index (GI), gingival sulcus bleeding index (SBI), and levels of inflammatory factors in gingival crevicular fluid, including interleukin-1β (IL-1β) and soluble intercellular adhesion molecule-1 (sICAM-1). Results:The completion time of treatment in the Group A was longer than that in the group B [(34.62±4.28)months vs (28.93±3.11)months] ( P<0.01). After treatment, the incidence of root resorption in the group A was 50.96%, while in the group B it was 78.00%. The group A was significantly lower than the group B ( P<0.05), with no root resorption greater than 3 mm in the group A and 0.50% in the group B. After treatment, the levels of PLI, GI, SBI, and IL-1β and sICAM-1 in gingival crevicular fluid increased in both groups, with the group A being lower than group B [(1.26±0.39)points vs (1.73±0.54)points, (1.33±0.25)points vs (2.06±0.46)points, (1.73±0.40)points vs (2.48±0.50)points, (173.74±25.81)ng/ml vs (196.33±31.52)ng/ml, (42.28±5.16)μg/L vs (56.59±7.38)μg/L] (all P<0.05). Conclusions:Although invisible orthodontic appliances without brackets cannot shorten the completion time of treatment, they have advantages in inhibiting root resorption, improving periodontal health, and reducing inflammatory reactions. Clinically, appropriate appliances can be selected based on the specific situation of patients.

Objective:To explore the effectiveness of the Shewhart control chart-based assessment and early warning system in prevention of medical device-related pressure injury(MDRPI).Methods:152 critically ill patients admitted to Hebei Central Hospital from January 2020 to December 2021 were selected and divided into a control group and an observation group based on different methods of assessing MDRPI risk,with 76 cases in each group.The control group adopted the Braden scale to assess the risk of MDRPI.The observation group adopted a safety early warning system based on Shewhart control charts to assess the risk of MDRPI in patients.Nursing measures were undertaken according to MDRPI risk grade in both groups.The occurrence of adverse events of MDRPI,nursing safety quality and nursing comprehensive quality were compared between the two groups.Results:The incidence rate of head,neck and face adverse events of MDRPI and the total incidence of adverse events of MDRPI of the patients in the observation group were lower than those in the control group(x2=4.802,5.758,P<0.05).The safety quality and comprehensive quality of nursing of 20 nurses in the observation group were higher than those in the control group(t=6.654,7.172,P<0.05).Conclusion:The application of assessment and early warning system based on Shewhart control chart in clinical nursing management can effectively reduce the incidence of MDRPI adverse events and improve the quality of nursing safety and comprehensive nursing.