Objective To explore the role of X chromosome encoded epigenetic regulator UTX in NK cell-mediated anti-tumor activity.Methods Male Ncr1-iCre mice were crossed with female UTXfl/fl mice to generate F1 Ncr1-iCre+UTXfl/-male mice,which were further crossed with female UTXfl/fl mice to obtain male Ncr1-iCre-UTX fl/-control mice(M-Con)and NK-specific deletion of UTX male mice Ncr1-iCre+UTXfl/-(M-KO),as well as female Ncr1-iCre-UTXfl/fl control mice(F-Con)and UTX-deficient female mice Ncr1-iCre+UTXfl/fl(F-KO).UTX-deficient mice were injected with melanoma cell line B16F10 via tail vein to observe pulmonary metastatic tumor nodules.Moreover,flow cytometry was applied to detect the proportion and quantity of pulmonary NK cells(CD3-CD19-NK1.1+),maturation makers KLRG1 and CD11b,activation receptors NKG2D and CD69,and effector molecules,including perforin,granzyme B,CD107a,and IFN-γ.Then pulmonary NK cells were sorted and co-cultured with B16F10 cells,and the apoptosis of the melanoma cells was measured with flow cytometry.Results Compared with the M-Con mice,the M-KO mice presented less number of pulmonary tumor nodules(P<0.05),increased proportion and quantity of NK cells in the tumor microenvironment(P<0.01),though no obvious changes in the ratio of NK maturation makers KLRG1 to CD11b,enhanced expression level of cytotoxic molecule perforin(P<0.01),but no changes in the expression of effector molecule granzyme B,degranulation marker CD107a and cytokine IFN-γ in NK cells.Co-culture of NK cells and B16F10 cells promoted the apoptosis of tumor cells(P<0.05).Compared with the F-Con mice,the F-KO mice had no statistical difference in the number of pulmonary tumor nodules,but larger proportion and number of NK cells(P<0.05),decreased ratio of KLRG1 to CD11b(P<0.01),elevated level of perforin but decreased levels of granzyme B,CD107a and IFN-γ in NK cells(P<0.01).The co-culture of NK cells and B16F10 cells reduced the apoptosis of tumor cells in F-KO female mice(P<0.05).Conclusion NK-specific deletion of UTX regulates pulmonary metastasis of melanoma in a sex-dependent manner.

Objective To investigate the changes in blood microbiota in patients with high altitude polycythemia(HAPC)and the correlation with the risk of HAPC.Methods A cross-sectional trial was carried out among 41 HAPC patients(HAPC group)and 41 healthy plateau individuals(control group)who took physical examination in the Health Management Department of No.953 Hospital of PLA Army in 2021.High-throughput sequencing technology was used to detect the V3-V4 variable region of the 16S ribosomal RNA(16S rRNA)gene in the blood smaples,and the composition and difference of the blood microbiota were compared and analyzed between the 2 groups.Results All the participants were male and Han people,and there were no significant differences in baseline data such as age,body mass index and plateau migration time between the 2 groups(P＞0.05).The α-diversity of blood microbiota in the HAPC group,including the Simpson index(0.931±0.005 vs 0.907±0.008,P＜0.05),Goods Coverage index(0.998±0.001 vs 0.997±0.001,P＜0.001)and Pielou index(0.597±0.011 vs 0.567±0.009,P＜0.05)were significantly higher than those in the control group.Meanwhile,obvious difference was observed in the β diversity between the 2 groups(P＜0.01).The relative abundance analysis of bacteria showed that Pelomonas(0.046±0.004 vs 0.033±0.003,P＜0.05),Azospirillum(0.046±0.006 vs 0.021±0.003,P＜0.01),Acidovorax(0.032± 0.003 vs 0.019±0.002,Azospirillum(0.046±0.006 vs 0.021±0.003,P＜0.01)and Acidovorax(0.032± 0.003 vs 0.019±0.002,P＜0.05)were statistically higher in the HAPC group than the control group.LEfSe analysis showed that the characteristic blood microbiota of the HAPC group were α-Proteobacteria,and those of control group were Trichospiridae.Conclusion Significant changes are found in diversity,relative abundance and characteristic bacteria of the blood microbiota between the HAPC patients and healthy people at the high altitude,which might be closely associated with the occurrence and development of HAPC.

Lung cancer is the cancer type with the highest incidence rate and mortality among malignant tumors in China.Tumor associated macrophages(TAMs)are closely related to the occurrence,development,invasion and metastasis,and treatment tolerance of lung cancer.This article explored the etiology and pathogenesis of lung cancer in TCM,as well as the key role of TAMs in lung cancer.It was found that the local imbalance of yin and yang in TAMs,as well as the overall imbalance of yin and yang in the tumor microenvironment and whole body,were important reasons for the formation and progression of lung cancer.In the progression and sequelae of lung cancer,M1 and M2 type TAMs each plays different roles and has different yin and yang properties.Both of them maintain a constantly developing and changing state of mutual use,opposing constraints,and balance of growth and decline.Based on the yin-yang theory in TCM,according to the progression of lung cancer and the imbalance of yin and yang,rational selection and medication can adjust the phenotype of TAMs,promote the overall balance of yin and yang,and provide reference for the clinical prevention and treatment of lung cancer.

Objective To investigate the application value of ultrasound combined with MRI in the diagnosis of fetal urinary system abnormalities.Methods The clinical data of 647 cases of fetal urinary system abnormalities suspected by prenatal ultrasound were ana-lyzed retrospectively.All pregnant women underwent MRI examination within 2 days after ultrasound examination.Using pathology and follow-up as the gold standard,the accuracy and imaging features of ultrasound and MRI in detecting fetal urinary system abnor-malities were analyzed.Results Among 600 cases confirmed by pathology and follow-up,the accuracy of MRI,ultrasound and com-bined diagnosis of fetal urinary system abnormalities were 96.50％,96.67％,97.00％,sensitivity were 95.28％,96.23％,98.11％,and specificity were 96.76％,96.76％,96.76％,respectively.There were no significant differences in accuracy,sensitivity,specificity,positive predictive value and negative predictive value between MRI,ultrasound and combined diagnosis(P＞0.05).The area under the curve(AUC)of MRI,ultrasound and combined diagnosis of fetal urinary system abnormalities were 0.960,0.965 and 0.974,respectively,with no statistical significance(P＞0.05).Conclusion Compared with prenatal ultrasound,MRI also has a higher accuracy(96.50％)in the diagnosis of fetal urinary system abnormalities,and can be used as an important supplement to prenatal ultrasound.

Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on MASLD. Methods: Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on MASLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4+ T cells were isolated and stimulated to demonstrate our findings. Results: In this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of MASLD. In addition, this study revealed that in addition to the canonical TGF-β/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in MASLD progression. Conclusions Ursolic acid could improve immune inflammation in MASLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)pre-sents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2％dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2％ DSS-induced Rag1-/-mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage indepen-dently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned me-dium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

We retrospectively analyzed therapy efficacy and the adverse reactions of 10 patients suffering from systemic lupus erythematosus (SLE) with intestinal involvement treated with rituximab (RTX). Patients were hospitalized in the Department of Rheumatology and Immunology of the First Medical Center of PLA General Hospital from January 2015 to January 2023. Among the 10 patients, two were men and eight were women. The age of the cohort was (41.9±8.8) years. The age at disease onset was (28.8±9.2) years. The total course of the SLE diagnosis was(109.6±59.9) months. The course of the diagnosis of SLE with intestinal involvement was (89.3±50.2) months. The time from the appearance of intestinal symptoms to the diagnosis of SLE with intestinal involvement was 1.5 (1.0,8.0) months. The time from the diagnosis of SLE with intestinal involvement to RTX use was 13.0 (1.0,46.3) months. Follow-up duration after application of RTX treatment was (55.3±28.4) months. There were five cases of abdominal pain, four cases of abdominal distension, nine cases of diarrhea, three cases of nervous-system involvement, nine cases of lupus nephritis, and seven cases of serositis. All 10 patients underwent computed tomography and radiology of the abdomen. Eight patients had intestinal-wall edema, seven suffered intestinal dilation, four had target signs, three suffered congestion of mesenteric blood vessels, eight had increased mesenteric-fat density, and six had false intestinal obstruction. All 10 patients showed a low level of complement C3 (250-750 mg/L). Nine cases showed a low level of complement C4 (10-90 mg/L). The SLE disease activity index 2000 (SLEDAI-2K) at baseline in 10 patients was 20.5 (17.8, 30.0). After receiving RTX (0.5 g: day 1, day 14, or 375 mg/m 2: day 1, day 14) induction treatment, the intestinal symptoms of 10 cases were relieved completely. Four patients had adverse reactions, of which three received a high-dose glucocorticoid combined with RTX treatment simultaneously. Adverse reactions manifested mainly as a reduced level of IgG and infection with herpes simplex virus in one case, reduced level of IgG and lung infection in one patient, lung infection in one case, and reduced IgG level in one patient. RTX may an efficacious treatment strategy for patients suffering from refractory SLE with intestinal involvement.

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Postoperative delirium(POD),a common surgical complication,refers to the acute and fluctuating disturbance in attention and awareness after surgery,which seriously affects the recovery and is one of the predictors of poor prognosis of patients.At present,preoperative anxiety is common in periopera-tive patients.As the independent risk factors for POD,preoperative anxiety plays an important role in the occurrence and development of POD.Taking active and reasonable intervention measures for patients with preoperative anxiety may effectively reduce the occurrence of POD.This paper reviews the effects of preoper-ative anxiety on POD,focusing on its mechanism and prevention methods,in order to explore the relation-ship between preoperative anxiety and POD,which might provide new ideas for the clinic.

The study aimed to analyze the efficacy and safety of rituximab in the treatment of 23 cases of lupus nephritis and explore the prospect of half-dose rituximab in lupus nephritis treatment. Twenty-three patients with lupus nephritis hospitalized in the Department of Rheumatology and Immunology at the First Medical Center of the PLA General Hospital from May 2013 to December 2021 were selected. Eighteen patients received rituximab 375 mg/m 2 on the first and 14th days, 5 patients received 500 mg of rituximab on the first and 14th days, and rituximab was used as needed 6 months later. Methylprednisolone (80-120 mg) was given together with rituximab. Afterward, 1 mg/kg prednisone was used for 4 weeks, which was progressively tapered to maintenance doses or discontinued. B lymphocyte level, renal function, 24-h urine protein level, and systemic lupus erythematosus (SLE) disease activity index 2000 (SLEDAI2K) score before and after treatment were recorded. The efficacy and adverse reactions were analyzed. The results showed that 11 patients suffered from renal insufficiency [creatinine (162.7±58.6) μmol/L ] at baseline, while the creatinine level of 9 patients returned to normal 12 months after the treatment [ (66.3±10.1)μmol/L ]. Normal renal function of the other 12 patients was maintained during treatment. After 12 months, the 24-h urine protein level decreased from 4.00 (2.00,6.80) g in the baseline period to 0.10 (0.08,0.40) g. SLEDAI2K score decreased from 22 (18,26) in the baseline period to 3 (0,6) 12 months after the treatment. The B lymphocyte level reached 0.00 (0.00,0.01)% at 3 months. Of 23 patients, 13 patients achieved complete remission, and 7 patients achieved partial remission after 6 months of rituximab treatment. Five patients experienced adverse reactions related to rituximab, including 1 case of transfusion reaction, 1 case of perioral herpes with pulmonary infection, and 3 cases of decreased IgG levels. Therefore, rituximab regimen used in this study can be an effective treatment strategy for lupus nephritis.