[Experimental study on the inhibition of the NLRP3 signaling pathway with Shengsan Jiedu Huayu decoction to alleviate inflammatory injury in rats with acute-on-chronic liver failure].

Objective: To observe the therapeutic effect of Shengsan Jiedu Huayu decoction in alleviating inflammatory liver injury in rats with acute-on-chronic liver failure (ACLF) and its effect on the activation intensity for the NLRP3 signaling pathway. Methods: 63 SD rats were randomly divided into a blank group, a model group, and low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction (7.29 g/kg/d, 14.58 g/kg/d, and 29.16 g/kg/d). The ACLF rat model was replicated using carbon tetrachloride combined with d-galactosamine and lipopolysaccharide. Different dose gradients of the Shengsan Jiedu Huayu decoction were used for a five-day intervention treatment, and then rat serum and tissue samples were collected. A biochemical analyzer was used to detect the serum levels of ALT, AST, and TBIL in rats. ELISA was used to detect serum IL-18 and IL-1ß content. HE staining was used to observe histomorphological changes in liver tissue. Immunohistochemistry was used to detect GSDMD expression in liver tissue. Western blot and PCR were used to detect NLRP3, Caspase1, ASC, TLR4, IL-1ß, IL-18 protein, and mRNA expression levels.The groups were compared using analysis of variance and the rank-sum test. Results: Compared with the blank group, the model group's rat liver tissue was severely injured. Serum levels of ALT, AST, and TBIL, inflammatory factors IL-1ß and IL-18, and the GSDMD protein expression level, NLRP3 expression level, TLR4, caspase 1, ASC, IL-1ß, IL-18 protein, and mRNA (P<0.01) were all significantly increased in the model than the blank group (P<0.01). Additionally, compared with the model group, the low-, medium-, and high-dose groups of Shengsan Jiedu Huayu decoction had improved liver tissue injury in ACLF rats, while the serum levels of ALT, AST, TBIL, IL-1ß, IL-18, liver tissue GSDMD protein, NLRP3, TLR4, caspase 1, and ASC expressions were all lower in the different dose gradients of the Shengsan Jiedu Huayu decoction than the model group, with the most evident reduction in the high-dose group (P<0.01). Conclusion: Shengsan Jiedu Huayu decoction can weaken the activation intensity of the NLRP3 signaling pathway, alleviate liver tissue pathological injury, reduce inflammatory factor release, and alleviate inflammatory liver injury in ACLF rats.

[Preparation of a dual-specific antibody targeting human CD123 and exploration of its anti-acute myeloid leukemia effects].

Objective: To construct a novel dual-specific antibody targeting human CD123 (CD123 DuAb) and study its effects in acute myeloid leukemia (AML) . Methods: Based on the variable region of the CD123 monoclonal antibody independently developed at our institution, the CD123 DuAb expression plasmid was constructed by molecular cloning and transfected into ExpiCHO-S cells to prepare the antibody protein. Through a series of in vitro experiments, its activation and proliferation effect on T cells, as well as the effect of promoting T-cell killing of AML cells, were verified. Results: ① A novel CD123 DuAb plasmid targeting CD123 was successfully constructed and expressed in the Expi-CHO eukaryotic system. ②The CD123 DuAb could bind both CD3 on T cells and CD123 on CD123(+) tumor cells. ③When T cells were co-cultured with MV4-11 cells with addition of the CD123 DuAb at a concentration of 1 nmol/L, the positive expression rates of CD69 and CD25 on T cells were 68.0% and 44.3%, respectively, which were significantly higher than those of the control group (P<0.05). ④Co-culture with CD123 DuAb at 1 nmol/L promoted T-cell proliferation, and the absolute T-cell count increased from 5×10(5)/ml to 3.2×10(6)/ml on day 9, and CFSE fluorescence intensity decreased significantly. ⑤ With the increase in CD123 DuAb concentration in the culture system, T-cell exhaustion and apoptosis increased. When the CD123 DuAb was added at a concentration of 1 nmol/L to the culture system, the proportion of CD8(+) PD-1(+) LAG-3(+) T cells was 10.90%, and the proportion of propidium iodide (PI) (-) Annexin Ⅴ(+) T cells and PI(+) Annexin Ⅴ(+) T cells was 18.27% and 11.43%, respectively, which were significantly higher than those in the control group (P<0.05). ⑥ The CD123 DuAb significantly activated T cells, and the activation intensity was positively correlated with its concentration. The expression rate of CD107a on T cells reached 16.05% with 1 nmol/L CD123 DuAb, which was significantly higher than that of the control group (P<0.05). ⑦The CD123 DuAb promoted cytokine secretion by T cells at a concentration of 1 nmol/L, and the concentration of IFN-γ and TNF-α in the supernatant of the co-culture system reached 193.8 pg/ml and 169.8 pg/ml, respectively, which was significantly higher than that of the control group (P<0.05). ⑧When CD123 DuAb was added at a concentration of 1 nmol/L to the co-culture system of T cells and CD123(+) tumor cells, the killing intensity of T cells significantly increased, and the residual rates of CD123(+) MV4-11 cells, CD123(+) Molm13 cells, and CD123(+) THP-1 cells were 7.4%, 6.7%, and 14.6% on day 3, respectively, which were significantly lower than those in the control group (P<0.05) . Conclusion: In this study, a novel CD123 DuAb was constructed and expressed. In vitro experiments verified that the DuAb binds to CD123(+) tumor cells and T cells simultaneously, promotes T-cell activation and proliferation, and facilitates their anti-leukemia effect, which provides a basis for further clinical research.

[Molecular mechanism analysis of a family with hereditary coagulation F â ª deficiency caused by compound heterozygous mutations].

A 34 year old female patient was scheduled to undergo surgical resection due to a "breast nodule". Preoperative examination revealed an activated partial thromboplastin time (APTT) of 66.2 seconds, coagulation factor Ⅺ activity (FⅪ: C) of 2%, and FⅪ antigen (FⅪ: Ag) of 40.3%. The patient and family members showed no abnormal bleeding symptoms. Diagnosed as hereditary coagulation factor Ⅺ deficiency. Genetic testing revealed that the F11 gene had a heterozygous nonsense mutation in exon 10, c.1107C>A (p.Tyr351stop), and a heterozygous missense mutation in exon 13, c.1562A>G (p.Tyr503Cys). The father and son were p Heterozygous carriers of Tyr351stop mutation, while the mother and daughter are p Heterozygous carriers of Tyr503Cys mutations. The in vitro expression results showed that p The Tyr351stop mutation resulted in a significant decrease in the transcription level of F11 gene, while p The Tyr503Cys mutation has no effect on the transcription level and protein expression level of F11 gene, but it leads to a significant decrease in the level of FⅪ:C in the cell culture supernatant.

Resolvin D1 inhibits T follicular helper cell expansion in systemic lupus erythematosus.

OBJECTIVE: Resolvin D1 (RvD1) is one of the specialized pro-resolving lipid mediators, which control inflammation resolution and regulate immune responses. Previous research showed that RvD1 could block the progression of systemic lupus erythematosus (SLE). However, the detailed mechanism remains to be fully understood. METHOD: Plasma RvD1 levels, and proportions of T follicular helper cells (Tfh cells) were measured in SLE patients and healthy controls. Plasma RvD1 levels and proportions of Tfh cells were quantitated in an MRL/lpr mouse model of lupus treated with RvD1. Naïve CD4+ T cells were purified from MRL/lpr mice to study the effect of RvD1 on Tfh cell differentiation in vitro. RESULTS: In patients, there were significant negative correlations between plasma RvD1 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, as well as between plasma RvD1 and anti-double-stranded DNA antibody levels, and numbers of peripheral Tfh cells and plasma cells. In MRL/lpr mice, the expected amelioration of disease phenotype and inflammatory response with RvD1 treatment correlated with decreased percentages of Tfh cells and plasma cells. In addition, the differentiation and proliferation of Tfh cells were markedly suppressed by RvD1 in vitro. CONCLUSION: RvD1 may control SLE progression through the suppression of Tfh cell differentiation and subsequent inhibition of B-cell responses.

Quercetin ameliorates lipid deposition in primary hepatocytes of the chicken embryo.

1. The accumulation of excessive fat plays a role in the development of non-alcoholic fatty liver disease (NAFLD) and phytogenic feed additives have the potential to ameliorate this. This study involved the isolation and culture of primary hepatocytes from chicken embryos to establish a model of hepatic steatosis induced by oleic acid/dexamethasone (OA/DEX). Lipid accumulation and cell viability were assessed using Nile Red staining, Oil Red O staining and cell count Kit -8 (CCK8) following treatment with varying concentrations of quercetin (Que). The potential mechanism by which Que exerts its effects was preliminarily investigated.2. The results indicated that OA effectively treated lipid accumulation in hepatocytes. There was no notable variance in cell proliferation between the normal and OA/DEX groups when subjected to Que treatment at concentrations of 1000 ng/ml and 10 000 ng/ml. Triglycerides and cholesterol (low and high density) decreased with Que treatment, with the most substantial reduction observed at 10 000 ng/ml.3. Gene expression levels decreased to levels similar to those in the control groups. Western blot data demonstrated that sterol regulatory element-binding protein 1 (SREBP-1) protein expression correlated with its mRNA expression level. Que mitigated lipid accumulation through the alpha serine/threonine protein kinase (AKT) and extracellular signal-regulated kinase (ERK) pathways. Expression levels of lipid-related genes (APOB, PPARα, CYP3A5 and SREBP-1) decreased to levels similar to the control groups. Western blot data demonstrated that the SREBP-1 protein expression correlated with its mRNA expression level.4. Supplementation with Que ameliorated lipid accumulation through AKT and ERK signalling pathway in OA/DEX-induced high-fat hepatocytes.

[Progress in lipoarabinomannan antigen detection for tuberculosis diagnosis in people living with HIV/AIDS].

Tuberculosis (TB) is the leading cause of death among people living with HIV/AIDS (PLWHA), posing a significant disease burden. Early TB screening in PLWHA is a key intervention to reduce transmission and control disease progression. ​Lipoarabinomannan (LAM) is a glycolipid of Mycobacterium tuberculosis (MTB) that can be detected in the urine of tuberculosis patients. LAM is useful for the rapid and accurate diagnosis of tuberculosis. This article reviews LAM and its application and limitations in the diagnosis of PLWHA, hoping to provide a reference for the diagnosis of tuberculosis in PLWHA.

[Exploration and contemplation of homogenized education of specialists in pulmonary and critical care medicine at member hospitals of a hospital consortium].

Talent construction is the cornerstone to the establishment of a high-quality, homogeneous healthcare system in a healthcare consortium. Pulmonary and critical care medicine (PCCM) as the first pilot specialty, the standardized training of PCCM specialists has started and achieved remarkable results. The consortium member hospitals' physician specialist education is an important complement to PCCM training. The establishment of the consortium provides a new form of the education of physicians in PCCM, with the advantages of high quality teaching, wide coverage of staff and throughout the career development process. This article summarized the current status of physician specialty education in the member hospitals of the consortium, and further proposes the goal of homogenized specialty education for physicians in the member hospitals. And it analyzed in depth the problems that existed in the practice of training for hospital consortium member hospitals specialists, such as non-uniform level of instruction, non-systematic content of training, limited sources of teaching cases, and lack of teaching materials and equipment. For the medical consortium member hospital physician specialty education of in-depth thinking, we put forward the corresponding countermeasures. The aim of this study is to explore the homogenization of the specialty education system of pulmonary and critical care medicine in the member hospitals, in order to comprehensively improve the medical level of respiratory specialists in the member hospitals of the medical consortium.

Global Burden of Alzheimer's Disease and Other Dementias Attributed to High Fasting Plasma Glucose from 1990 to 2019.

BACKGROUND: Burden of Alzheimer's disease (AD) and other dementias have grown rapidly over the decades, and high fasting plasma glucose (HFPG) was one of the well-established risk factors. It is urgently needed to estimate the global burden of AD and other dementias attributable to high fasting plasma glucose between regions, countries, age groups, and sexes to inform development of effective primary disease prevention strategies and intervention policies. METHODS: The burden of AD and other dementias attributable to HFPG was estimated based on a modeling strategy using the Global Burden of Disease Study 2019 dataset. The disease burden and time trend globally and by region, country, development level, age group, and sex were evaluated. RESULTS: The number of AD and other dementias-related deaths attributable to HFPG increased from 42,998.23 (95% uncertainty interval, UI: 4459.86-163,455.78, the year of 1990) to 159,244.53 deaths (95% UI 18,385.23-583,514.15, the year of 2019). The age-standardized death rate increased from 1.69 (95% UI 0.18-6.54) in 1990 to 2.24 (95% UI 0.26-8.24) in 2019. The burden was higher in more developed regions. The burden in women was double that in men, that HFPG-attributable AD and other dementias caused 99,812.79 deaths (95% UI 9005.67-387,160.60) in women and 59,431.74 deaths (95% UI 5439.02-214,819.23) in men, with age-standardized death rate of 2.27 (95% UI 0.20-8.79) per 100,000 population in women and 2.20 (95% UI 0.20-8.00) in men. CONCLUSION: Findings from the current study emphasizes the urgent requirement for targeted interventions in high-development regions, as well as the importance of proactive measures in middle-development countries in protection of AD and other dementias. The gender disparity necessitates the integration of gender-specific considerations in targeted approaches in prevention of AD and other dementias.

[Analysis on the ultrasonic characteristics of tonsillar lymphoma].

Objective: To analyze the ultrasonic features of tonsillar lymphoma to improve the diagnostic accuracy. Methods: The clinical, pathological and ultrasonic data of nine patients with tonsillar lymphoma confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital during June 2015 and June 2022 were analyzed retrospectively, and the characteristics of their ultrasonic images were summarized. Results: All 9 cases of tonsil lymphoma were unilateral tonsil disease, including 4 cases on the left side and 5 cases on the right side. The average maximum diameter of tonsil lymphoma in 9 cases was 4.32 cm. There were 3 cases with simultaneous involvement of tonsil and cervical lymph nodes, all of which were ipsilateral lymph nodes. Gray scale ultrasound showed that the lesions were hypoechoic, with clear boundaries in 7 cases and unclear boundaries in 2 cases. The shape was full and irregular in 5 cases and oval in 4 cases. The echo was uniform in 7 cases and uneven in 2 cases. Color Doppler ultrasonography showed abundant internal blood flow signal in 1 case, a little dotted linear internal blood flow signal in 5 cases, and no obvious internal blood flow signal in 3 cases. Conclusions: The ultrasonic features of tonsillar lymphoma include hypoechoic area, clear boundary, full shape, irregular and uniform internal echo, no or low linear signal of internal blood flow. Ultrasonography is of great value in the diagnosis of this disease and can help clinical decision-making.

[Mechanism of noise induced hidden hearing loss based on proteomics].

Objective: To explore the mechanism of noise-induced hidden hearing loss by proteomics. Methods: In October 2022, 64 SPF male C57BL/6J mice were divided into control group and noise exposure group with 32 mice in each group according to random sampling method. The noise exposure group was exposed to 100 dB sound pressure level, 2000-16000 Hz broadband noise for 2 h, and the mouse hidden hearing loss model was established. Auditory brainstem response (ABR) was used to test the change of hearing threshold of mice on the 7th day after noise exposure, the damage of basal membrane hair cells was observed by immunofluorescence, and the differentially expressed proteins in the inner ear of mice in each group were identified and analyzed by 4D-Label-free quantitative proteomics, and verified by Western blotting. The results were statistically analyzed by ANOVA and t test. Results: On the 7th day after noise exposure, there was no significant difference in hearing threshold between the control group and the noise exposure group at click and 8000 Hz acoustic stimulation (P>0.05) . The hearing threshold in the noise exposure group was significantly higher than that in the control group under 16000 Hz acoustic stimulation (P<0.05) . Confocal immunofluorescence showed that the basal membrane hair cells of cochlear tissue in noise exposure group were arranged neatly, but the relative expression of C-terminal binding protein 2 antibody of presynaptic membrane in middle gyrus and basal gyrus was significantly lower than that in control group (P<0.05) . GO enrichment analysis showed that the functions of differentially expressed proteins were mainly concentrated in membrane potential regulation, ligand-gated channel activity, and ligand-gated ion channel activity. KEGG pathway enrichment analysis showed that differentially expressed proteins were significantly enriched in phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) signaling pathway, NOD-like receptor signaling pathway, calcium signaling pathway, etc. Western blotting showed that the expression of inositol 1, 4, 5-trisphosphate receptor 3 (Itpr3) was increased and the expression of solute carrier family 38 member 2 (Slc38a2) was decreased in the noise exposure group (P<0.05) . Conclusion: Through proteomic analysis, screening and verification of the differential expression proteins Itpr3 and Slc38a2 in the constructed mouse noise-induced hidden hearing loss model, the glutaminergic synaptic related pathways represented by Itpr3 and Slc38a2 may be involved in the occurrence of hidden hearing loss.

[Diquat poisoning leads to ARDS: report of two cases].

Diquat (DQ) is a non-selective, foliage-applied herbicide that is known to cause liver and kidney damage, while the impact on the lungs is relatively mild. Current domestic and international reports on diquat poisoning primarily focus on liver and kidney injuries, with limited documentation of cases leading to acute respiratory distress syndrome (ARDS) and lung damage. This paper presents a retrospective analysis of two documented cases of diquat poisoning, both exhibiting ARDS. In both cases, the condition rapidly progressed upon the onset of ARDS despite aggressive treatment, ultimately resulting in the death of the patients.

[Analysis of the safety, accuracy, and factors influencing bleeding complications in CT-guided puncture biopsy of brain occupying lesions].

Objective: To investigate the safety and accuracy of CT-guided intracranial puncture biopsy and the possible influencing factors of postoperative bleeding complications. Methods: A case series study. A retrospective analysis was conducted on 101 patients who underwent CT-guided intracranial puncture biopsy at the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2021. The basic data of patients and the safety and accuracy of CT-guided intracranial puncture biopsy were analyzed statistically. Univariate and multivariate logistic regression analysis were used to screen the influencing factors of bleeding complications in CT-guided intracranial puncture biopsy, and the bleeding complications in glioma subgroup were analyzed. Results: Among the 101 patients, 53 were males and 48 were females, aged (53.7±17.2) years. The average diameter of intracranial lesions was (3.5±1.4) cm, while the vertical distance from the lesion to the meninges was (2.4±1.7) cm. The needle's intracranial depth reached (3.2±1.8) cm, with adjustments averaging (3±1) occurrences and an average procedural duration of (40.2±12.9) minutes. Pathological diagnoses included glioma (36 cases), gliosis (3 cases), lymphoma (32 cases), metastatic tumors (7 cases), inflammatory lesions (13 cases), and 10 indeterminate cases. The positive rate of puncture pathology was 90.1% (91/101), and the diagnostic coincidence rate was 94.0% (78/83). The incidence of bleeding complications in CT-guided intracranial puncture biopsy was 26.7% (27/101), of which 23 cases had small intratoma or needle path bleeding, 4 cases had massive bleeding, and 2 cases died. The patients were divided into bleeding group (n=27) and no bleeding group (n=74), according to the presence or absence of bleeding. The results of univariate logistic regression analysis showed that thrombin time≥15 s and the number of needle adjustment were the factors affecting the occurrence of bleeding complications (both P<0.05), and the results of multivariate logistic regression showed that thrombin time≥15 s was the related factor for bleeding. Patients with thrombin time≥15 s had a 3.045 times higher risk of bleeding than those with thrombin time<15 s (OR=3.045,95%CI:1.189-7.799,P=0.020). Among the 101 patients, 36 cases of midbrain glioma were divided into low-grade glioma group (n=11) and high-grade glioma group (n=25) according to the pathological grade. Subgroup analysis showed that the risk of bleeding for high-grade gliomas was 9.231 times higher than that for low-grade gliomas (OR=9.231,95%CI:1.023-83.331,P=0.031). Conclusions: CT-guided intracranial puncture biopsy is safe and feasible with high accuracy. Complication rates are associated with thrombin time≥15 s, especially high-grade glioma, which increases the risk of postoperative bleeding.

[High expression of UBE2S promotes progression of hepatocellular carcinoma by increasing cancer cell stemness].

OBJECTIVE: To investigate the expression of the ubiquitination enzyme UBE2S in different cell types in hepatocellular carcinoma (HCC) microenvironment and its impact on proliferation and stemness of HCC cells. METHODS: TCGA and CPTAC database were used to analyze the transcriptional and promoter methylation levels and protein expressions of UBE2S in HCC. Specific expression patterns of UBE2S, intercellular communication and key transcription factors in different cell types were analyzed based on single-cell sequencing data from TISCH website. We further examined UBE2S expressions in clinical samples of HCC tissues, HCC cells and T cells using immunohistochemistry and immunofluorescence staining. We also tested the effects of UBE2S knockdown on stemness of HCC-LM3 and HepG2 cells using clone formation experiments and sphere formation assay. RESULTS: Analysis based on TCGA database suggested significant overexpression of UBE2S in both paired and non-paired tumor tissues (P < 0.001), and its transcriptional level increased with tumor grades. The methylation level of UBE2S promoter was significantly decreased in HCC (P < 0.001), and its transcription level increased obviously in HCC with TP53 mutation (P < 0.001). Analysis of CPTAC database also demonstrated overexpression of UBE2S protein in HCC tissues (P < 0.001). Three prognostic models suggested that HCC patients with high UBE2S expression had poorer prognosis (P < 0.001). Single-cell sequencing data analysis revealed high expressions of UBE2S in T cells and high intensities of interaction between endothelial cells, epithelial cells and fibroblasts in HCC microenvironment. Immunohistochemistry and immunofluorescence staining demonstrated high UBE2S expressions in clinical samples of HCC tissues, HCC cells and T cells. In HCC-LM3 and HepG2 cells, UBE2S knockdown significantly inhibited cell clone formation and tumor sphere formation (P < 0.05). CONCLUSION: UBE2S is highly expressed in T cells in HCC microenvironment in close correlation with a poor prognosis. High UBE2S expression promotes the stemness of HCC cells.

Genome-wide association study of growth curve parameters reveals novel genomic regions and candidate genes associated with metatarsal bone traits in chickens.

The growth and development of chicken bones have an enormous impact on the health and production performance of chickens. However, the development pattern and genetic regulation of the chicken skeleton are poorly understood. This study aimed to evaluate metatarsal bone growth and development patterns in chickens via non-linear models, and to identify the genetic determinants of metatarsal bone traits using a genome-wide association study (GWAS) based on growth curve parameters. Data on metatarsal length (MeL) and metatarsal circumference (MeC) were obtained from 471 F2 chickens (generated by crossing broiler sires, derived from a line selected for high abdominal fat, with Baier layer dams) at 4, 6, 8, 10, and 12 weeks of age. Four non-linear models (Gompertz, Logistic, von Bertalanffy, and Brody) were used to fit the MeL and MeC growth curves. Subsequently, the estimated growth curve parameters of the mature MeL or MeC (A), time-scale parameter (b), and maturity rate (K) from the non-linear models were utilized as substitutes for the original bone data in GWAS. The Logistic and Brody models displayed the best goodness-of-fit for MeL and MeC, respectively. Single-trait and multi-trait GWASs based on the growth curve parameters of the Logistic and Brody models revealed 4 618 significant single nucleotide polymorphisms (SNPs), annotated to 332 genes, associated with metatarsal bone traits. The majority of these significant SNPs were located on Gallus gallus chromosome (GGA) 1 (167.433-176.318 Mb), GGA2 (96.791-103.543 Mb), GGA4 (65.003-83.104 Mb) and GGA6 (64.685-95.285 Mb). Notably, we identified 12 novel GWAS loci associated with chicken metatarsal bone traits, encompassing 35 candidate genes. In summary, the combination of single-trait and multi-trait GWASs based on growth curve parameters uncovered numerous genomic regions and candidate genes associated with chicken bone traits. The findings benefit an in-depth understanding of the genetic architecture underlying metatarsal growth and development in chickens.

[Effect of LAG3 deficiency on natural killer cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis].

OBJECTIVE: To investigate the effect of LAG-3 deficiency (LAG3-/-) on natural killer (NK) cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis. METHODS: C57BL/6 mice, each weighing (20 ± 2) g, were divided into the LAG3-/- and wild type (WT) groups, and each mouse in both groups was inoculated with 3 000 E. multilocularis protoscoleces via the hepatic portal vein. Mouse liver and spleen specimens were collected 12 weeks post-infection, sectioned and stained with sirius red, and the hepatic lesions and fibrosis were observed. Mouse hepatic and splenic lymphocytes were isolated, and flow cytometry was performed to detect the proportions of hepatic and splenic NK cells, the expression of CD44, CD25 and CD69 molecules on NK cell surface, and the secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-4, IL-10 and IL-17A. RESULTS: Sirius red staining showed widening of inflammatory cell bands and hyperplasia of fibrotic connective tissues around mouse hepatic lesions, as well as increased deposition of collagen fibers in the LAG3-/-group relative to the WT group. Flow cytometry revealed lower proportions of mouse hepatic (6.29% ± 1.06% vs. 11.91% ± 1.85%, P < 0.000 1) and splenic NK cells (4.44% ± 1.22% vs. 5.85% ± 1.10%, P > 0.05) in the LAG3-/- group than in the WT group, and the mean fluorescence intensity of CD44 was higher on the surface of mouse hepatic NK cells in the LAG3-/- group than in the WT group (t = -3.234, P < 0.01), while no significant differences were found in the mean fluorescence intensity of CD25 or CD69 on the surface of mouse hepaticNK cells between the LAG3-/- and WT groups (both P values > 0.05). There were significant differences between the LAG3-/- and WT groups in terms of the percentages of IFN-γ (t = -0.723, P > 0.05), TNF-α (t = -0.659, P > 0.05), IL-4 (t = -0.263, P > 0.05), IL-10 (t = -0.455, P > 0.05) or IL-17A secreted by mouse hepatic NK cells (t = 0.091, P > 0.05), and the percentage of IFN-γ secreted by mouse splenic NK cells was higher in the LAG3-/- group than in the WT group (58.40% ± 1.64% vs. 50.40% ± 4.13%; t = -4.042, P < 0.01); however, there were no significant differences between the two groups in terms of the proportions of TNF-α (t = -1.902, P > 0.05), IL-4 (t = -1.333, P > 0.05), IL-10 (t = -1.356, P > 0.05) or IL-17A secreted by mouse splenic NK cells (t = 0.529, P > 0.05). CONCLUSIONS: During the course of E. multilocularis infections, LAG3-/- promotes high-level secretion of IFN-γ by splenic NK cells, which may participate in the reversal the immune function of NK cells, resulting in aggravation of hepatic fibrosis.

[Clinical characteristics and prognosis analysis of pulmonary sarcomatoid carcinoma].

Objective: To summarize the clinical characteristics, treatment, and outcomes of patients with pulmonary sarcomatoid carcinoma (PSC) in order to improve clinicians' understanding of this disease. Methods: The clinical data of patients diagnosed with PSC in our hospital from January 1, 2015 to November 30, 2023 were retrospectively analyzed. According to whether radical resection was performed, the patients were divided into resectable group and unresectable group. The characteristics and treatments of PSC in different groups were compared. The survival curves were drawn by Kaplan-Meier method to compare the prognosis of different groups of patients. Results: A total of 43 PSC patients were included, including 32 males, with an average age of (62.79±9.59) years, and 31 smokers. Peripheral-type tumors were more common, with imaging showing predominantly solid soft tissue masses, and the maximum diameter of the tumor was more than 5 cm in 14 patients. Among the 23 patients who underwent NGS gene testing, the KRAS mutation rate was 43.5%, the TP53 mutation rate was 30.4%, and the MET mutation rate was 8.7%, all of which were MET-14 exon skipping mutations. PD-L1 expression was detected in 13 patients, 10 of whom showed high expression. The median overall survival (mOS) of the 43 patients with PSC was 24.6 months (13.0-52.7 months). Among them, 22 patients underwent radical lobectomy plus mediastinal lymph node dissection, 13 patients had postoperative recurrence, and 7 patients died during follow-up. The median disease-free survival (mDFS) was 12.3 months, the mOS was not achieved and the 1-year OS rate was 77.3 %. Twenty-one patients had unresectable locally advanced or advanced stage, and 15 patients died. The mDFS was 2.5 months, the mOS was 6.2 months, and the 1-year OS rate was 42.9 %. Seventeen patients received immunotherapy, and 1 patient received targeted therapy with the MET inhibitor glumetinib. Conclusions: PSC has a higher incidence in the elderly, smokers, and males, is highly malignant and has a poor prognosis. Based on its molecular biological characteristics, PD-L1 expression and tumor molecular detection can be performed to guide treatment options.

[A case of HIV combined with Mycobacterium celatum infection].

Here, we reported the diagnosis and treatment of a case of HIV infected person complicated by an extremely rare infection with Mycobacterium celatum. Due to the similarity of homologous sequence regions between Mycobacterium celatum and Mycobacterium tuberculosis complex, the identification of conventional Mycobacterium species was incorrect, which was corrected after first-generation 16S rRNA sequencing. This report aimed to improve the clinical understanding of Mycobacterium celatum infection and the level of differential diagnosis between non-tuberculous mycobacterial disease and tuberculosis.

[Research progress in regional odontodysplasia].

Regional odontodysplasia (ROD) is a rare localized dental developmental anomaly. The typical clinical manifestations of ROD are abnormal tooth eruption, abnormal development of enamel and dentin. The radiographic characteristic is "ghost teeth". Its etiology still remains unknown. The care and treatment of a patient with ROD needs a multidisciplinary approach. And the treatment should be taken after the assessment of each individual case of ROD. This paper reviews the definition, etiology, epidemiological features, clinical manifestations, imaging features, dental microstructure and treatment strategies of ROD to provide reference for clinical diagnosis and treatment.