A 51-year-old male presented with nasal obstruction, followed by progressive hearing loss and blurred vision. Imaging identified space-occupying lesions in the paranasal sinuses, orbits, and paraspinal regions, while laboratory tests confirmed positive anti-proteinase 3 anti-neutrophil cytoplasmic antibody(PR3- ANCA) immunoglobulin G (IgG)and markedly elevated serum IgG4. Despite treatment with corticosteroids, immunosuppressants, and radiotherapy, the patient exhibited steroid dependency with relentless disease progression. Following multidisciplinary consultation, a diagnosis of inflammatory myofibroblastic tumor (IMT) coexisting with ANCA- associated vasculitis (AAV) was favored, though IgG4-related disease remained a critical differential. Ultimately, profound immunosuppression precipitated a severe herpesvirus infection, leading to disseminated intravascular coagulation and multiple organ dysfunction syndrome. This case underscores the rarity and diagnostic complexity of concurrent IMT and AAV, highlights the therapeutic dilemma of balancing primary disease control against fatal opportunistic infections, and emphasizes the critical role of multidisciplinary collaboration in the diagnosis and treatment of complex diseases.

Objective:To investigate role of miR-4738-3p in targeting tryptophan 2,3-dioxygenase 2(TDO2)to regulate energy metabolism and inhibit immune escape in thyroid cancer cells.Methods:A total of 68 cases of thyroid cancer tissues and their corresponding adjacent non-cancerous tissues were collected,expressions of miR-4738-3p and TDO2 in tissues and cell lines were de-tected by qRT-PCR,relationship between miR-4738-3p expression and clinicopathological characteristics was analyzed.Effects of miR-4738-3p and TDO2 on proliferation,migration,invasion,energy metabolism and immune escape of TPC-1 and BCPAP cells were examined through CCK-8,clone formation,wound healing,Transwell experiments,biochemical analyses,ELISA and NK cell co-culture experiments,targeting relationship between miR-4738-3p and TDO2 was validated by dual luciferase reporter gene assay.In vivo xenograft experiments and immunohistochemical detections were conducted to observe effects of miR-4738-3p on tumorigenesis and expression of immune escape-related proteins in TPC-1 and BCPAP cells.Results:miR-4738-3p was lowly expressed(P<0.05),while TDO2 was highly expressed in thyroid cancer(P<0.05).Tumor size,lymph node metastasis and TNM staging were correlated with expression of miR-4738-3p(P<0.05).Compared with miR-NC group,miR-4738-3p mimics group exhibited decreased prolifera-tion,clone formation,migration,invasion ability,glucose uptake,lactate production,ATP/ADP ratio,TDO2 mRNA and protein expressions,tumor volume,mass,Ki-67,TDO2 and PD-L1 expressions(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were increased(P<0.05).miR-4738-3p inhibitor group showed increased proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production,ATP/ADP ratio,TDO2 mRNA and protein expressions(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were decreased(P<0.05).Binding sites were identified between miR-4738-3p and TDO2,and their expression were negatively correlated(r=-0.485 3,P<0.001).Compared with sh-NC group,proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production and ATP/ADP ratio were decreased in sh-TDO2 group(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were increased(P<0.05).Compared with Scrambled group,proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production and ATP/ADP ratio were increased in TDO2 group(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were decreased(P<0.05).Conclusion:miR-4738-3p targets TDO2 to regulate energy metabolism,inhibiting thyroid cancer cell proliferation,metastasis and immune escape.

Objective:To investigate the application effect of BOPPPS+team-based learning (TBL) based on the concept of outcome-based education (OBE) in the teaching of infectious rash and fever illnesses in children.Methods:A total of 199 undergraduate students of the class 2019 in the five-year program of Department of Pediatrics in Chongqing Medical University were selected as subjects, and they were divided into experimental group with 99 students and control group with 100 students using a random number table. The students in the experimental group received BOPPPS+TBL teaching based on the OBE concept, while those in the control group received traditional teaching. After the end of the curriculum, scores were compared between the two groups, and a questionnaire survey was conducted for self-evaluation of teaching and learning effectiveness and the acceptance of teaching models. SPSS 22.0 was used to perform the t-test and the chi-square test. Results:The experimental group had a significantly higher score of the course than the control group [(88.08±5.31) vs. (85.62±8.44), P=0.014]. The questionnaire survey showed that compared with the control group, the experimental group had significantly higher scores of the self-evaluation of teaching effectiveness [(4.40±0.75) vs. (3.36±1.13), P<0.001] and learning effectiveness [(4.31±0.84) vs. (3.35±1.19), P<0.001]. In the experimental group, 96.96% (96/99) of the students believed that BOPPPS+TBL teaching based on the OBE concept could help students to master and understand the knowledge points, and 93.93% (93/99) of the students were willing to use this teaching model in future learning. Conclusions:BOPPPS+TBL teaching based on the OBE concept can help to achieve teaching objectives and significantly improve student satisfaction and learning outcomes.

Objective:To investigate role of miR-4738-3p in targeting tryptophan 2,3-dioxygenase 2(TDO2)to regulate energy metabolism and inhibit immune escape in thyroid cancer cells.Methods:A total of 68 cases of thyroid cancer tissues and their corresponding adjacent non-cancerous tissues were collected,expressions of miR-4738-3p and TDO2 in tissues and cell lines were de-tected by qRT-PCR,relationship between miR-4738-3p expression and clinicopathological characteristics was analyzed.Effects of miR-4738-3p and TDO2 on proliferation,migration,invasion,energy metabolism and immune escape of TPC-1 and BCPAP cells were examined through CCK-8,clone formation,wound healing,Transwell experiments,biochemical analyses,ELISA and NK cell co-culture experiments,targeting relationship between miR-4738-3p and TDO2 was validated by dual luciferase reporter gene assay.In vivo xenograft experiments and immunohistochemical detections were conducted to observe effects of miR-4738-3p on tumorigenesis and expression of immune escape-related proteins in TPC-1 and BCPAP cells.Results:miR-4738-3p was lowly expressed(P<0.05),while TDO2 was highly expressed in thyroid cancer(P<0.05).Tumor size,lymph node metastasis and TNM staging were correlated with expression of miR-4738-3p(P<0.05).Compared with miR-NC group,miR-4738-3p mimics group exhibited decreased prolifera-tion,clone formation,migration,invasion ability,glucose uptake,lactate production,ATP/ADP ratio,TDO2 mRNA and protein expressions,tumor volume,mass,Ki-67,TDO2 and PD-L1 expressions(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were increased(P<0.05).miR-4738-3p inhibitor group showed increased proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production,ATP/ADP ratio,TDO2 mRNA and protein expressions(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were decreased(P<0.05).Binding sites were identified between miR-4738-3p and TDO2,and their expression were negatively correlated(r=-0.485 3,P<0.001).Compared with sh-NC group,proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production and ATP/ADP ratio were decreased in sh-TDO2 group(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were increased(P<0.05).Compared with Scrambled group,proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production and ATP/ADP ratio were increased in TDO2 group(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were decreased(P<0.05).Conclusion:miR-4738-3p targets TDO2 to regulate energy metabolism,inhibiting thyroid cancer cell proliferation,metastasis and immune escape.

Objective:To investigate the application effect of BOPPPS+team-based learning (TBL) based on the concept of outcome-based education (OBE) in the teaching of infectious rash and fever illnesses in children.Methods:A total of 199 undergraduate students of the class 2019 in the five-year program of Department of Pediatrics in Chongqing Medical University were selected as subjects, and they were divided into experimental group with 99 students and control group with 100 students using a random number table. The students in the experimental group received BOPPPS+TBL teaching based on the OBE concept, while those in the control group received traditional teaching. After the end of the curriculum, scores were compared between the two groups, and a questionnaire survey was conducted for self-evaluation of teaching and learning effectiveness and the acceptance of teaching models. SPSS 22.0 was used to perform the t-test and the chi-square test. Results:The experimental group had a significantly higher score of the course than the control group [(88.08±5.31) vs. (85.62±8.44), P=0.014]. The questionnaire survey showed that compared with the control group, the experimental group had significantly higher scores of the self-evaluation of teaching effectiveness [(4.40±0.75) vs. (3.36±1.13), P<0.001] and learning effectiveness [(4.31±0.84) vs. (3.35±1.19), P<0.001]. In the experimental group, 96.96% (96/99) of the students believed that BOPPPS+TBL teaching based on the OBE concept could help students to master and understand the knowledge points, and 93.93% (93/99) of the students were willing to use this teaching model in future learning. Conclusions:BOPPPS+TBL teaching based on the OBE concept can help to achieve teaching objectives and significantly improve student satisfaction and learning outcomes.

Objective To investigate expression levels and clinical significance of annexin A2 and S100 calcium binding protein A10 (S100A10) in cerebrospinal fluid of patients with secondary intracranial infection after craniocerebral surgery. Methods A total of 120 patients with secondary intracranial infection after craniocerebral surgery were selected as test group, while 120 patients with no infection after craniocerebral surgery in the same period were selected as control group. The levels of Annexin A2 and S100A10 in cerebrospinal fluid were detected by enzyme-linked immunosorbent assay(ELISA). Pearson correlation analysis was applied to analyze the correlations of Annexin A2 and S100A10 with clinical indicators. Logistic regression analysis was applied to analyze the influencing factors of secondary intracranial infection after craniocerebral surgery. Receiver operator characteristic (ROC) curve was applied to analyze the predictive value of Annexin A2 and S100A10 levels for the occurrence of secondary intracranial infection after craniocerebral surgery. Results The proportions of diabetes and cerebrospinal fluid leakages, blood l actate dehydrogenase (LDH), cerebrospinal fluid Annexin A2 and S100A10 levels in the test group were higher than those in the control group (P < 0.05). Annexin A2 in cerebrospinal fluid of patients with intracranial infection was positively correlated with S100A10, LDH, and S100A10 level was positively correlated with LDH (P < 0.05). Multivariate Logistic regression analysis showed that diabetes, cerebrospinal fluid leakage, blood LDH, Annexin A2 and S100A10 in cerebrospinal fluid were independent influencing factors for secondary intracranial infection after craniocerebral surgery (P < 0.05). ROC results showed that the AUCs of Annexin A2 level or S100A10 level alone in cerebrospinal fluid and their combined prediction for secondary intracranial infection after craniocerebral surgery was 0.788, 0.768 and 0.865 respectively, the AUC of combined prediction was larger than that of the single prediction (P < 0.05). Conclusion The expression levels of Annexin A2 and S100A10 are increased in cerebrospinal fluid of patients with secondary intracranial infection after craniocerebral surgery, which are independent influencing factors for secondary intracranial infection after craniocerebral surgery. Their combination has higher predictive value for secondary intracranial infection after craniocerebral surgery.

[Objective]To study the mechanism of Quzhuo Tongbi Formula(QZTB)in improving bile acid metabolism disorder induced by high fat diet(HFD)in mice using serum metabolomics.[Methods]Male C57BL/6J mice were randomly divided into blank,HFD model and QZTB groups.Serum metabolomic analysis was performed using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS)technique to screen potential biomarkers.The key targets on the enriched pathway were verified using Real-time quantitative polymerase chain reaction(RT-qPCR)method.[Results]A total of 103 potential biomarkers were screened using serum metabolomics analysis,mainly enriched in bile acid bioanabolic pathway.QZTB treatment could significantly improve the bile acid metabolism disorder induced by HFD in mice.RT-qPCR results showed that compared with blank group,the expression levels of cholesterol 7-alpha hydroxylase(CYP7A1)and cytochrome P450 family 8 subfamily B member 1(CYP8B1)in liver tissue of HFD model group were inhibited(P<0.01),and the expressions of farnitol X receptor(FXR)and small heterodimeric partner(SHP)also decreased(P<0.01,P<0.01,P<0.001,P<0.01).After QZTB treatment,the levels of key enzymes such as CYP7A1 and CYP8B1 on the classical pathway increased(P<0.01,P<0.05).FXR-SHP pathway was activated(P<0.05),thereby sterol regulatory element binding protein-1C(SREBP-1C)and fatty acid synthase(FAS)were inhibited(P<0.01,P<0.001).[Conclusion]QZTB could improve bile acid metabolism disorder induced by HFD in obese mice,which be attributed to increasing the activity of key enzymes in the classical bile acid synthase,promoting the synthesis of primary bile acid,activating FXR-SHP pathway,and further regulating bile acid biosynthesis metabolism.

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.

Objective:To explore the incidence of hepatitis B virus (HBV) reactivation in the population with HBV associated liver cancer after receiving programmed death receptor 1 (PD-1) inhibitors combined with targeted therapy, and the prognostic differences between HBV reactivation and non reactivation populations during this treatment.Methods:A retrospective analysis was conducted on patients with primary liver cancer who received PD-1 inhibitor combined with targeted drugs treatment at the Zhongshan Hospital, Fudan University (Xiamen Branch) from January 2019 to June 2021. Clinical data such as age, sex, liver function status, cirrhosis, HBV DNA level, alpha fetoprotein, tumor stage, anti-tumor program and anti HBV program, tumor treatment response, progression free survival (PFS), and total survival (OS) were collected for t test, χ 2 test and Kaplan-Meier survival analysis. Results:A total of 66 enrolled patients were enrolled, of which 17 cases experienced HBV reactivation, with an incidence rate of 25.76%; The rates of HBV reactivation at 3 months, 6 months, 1 year, 2 years, and 3 years were 6.06%(4/66), 12.12%(8/66), 19.70%(13/66), 22.73%(15/66), and 25.76%(17/66), respectively. There was no significant difference between the HBV reactivation group and the non HBV reactivation group in age, sex, liver function status, cirrhosis, HBV DNA level, alpha fetoprotein, tumor stage, anti-tumor and anti HBV programs, objective response rate (ORR) and disease control rate (DCR) (all P>0.05). However, the PFS and OS of the HBV reactivation group were significantly lower than those of the non HBV reactivation group, at 4.00 months vs 8.50 months ( P=0.002) and 12.90 months vs 19.77 months ( P=0.014), respectively. Conclusions:Patients with primary live cancer who receive PD-1 inhibitor combined with targeted therapy are at risk of HBV reactivation, and those who experience HBV reactivation have significantly poorer tumor progression and survival prognosis compared with non HBV reactivated patients.