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.

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 explore the value of MR modulated flip angle technique in refocused imaging with extended echo train(MATRIX)contrast enhanced(CE)T1-weighted fluid attenuated inversion recovery(T1 FLAIR)for detecting skull metastases.Methods Forty-four patients with malignant tumors who underwent head MR scanning for screening skull metastasis were prospectively enrolled,and skull metastasis were then confirmed by pathology or imaging examinations,including MRI,CT,radionuclide bone imaging(BS),PET/CT and follow-up.Head MATRIX CE-T1 FLAIR(group A),3D gradient recalled echo_fast spin echo with magnetization preparation(GRE_fsp)CE-T1 FLAIR(group B)and fast spin echo(FSE)CE-T1 FLAIR(group C)images of all 44 cases were acquired.The subjective scores(including images quality and diagnostic confidence)and objective evaluation results of images were compared among groups.Taken BS or PET/CT results as standards,the efficacy of 3 kinds of images for detecting skull metastases was calculated.Results The subjective scores of images quality and diagnostic confidence,as well as signal-to-noise ratio(SNR)in group A and C were all higher than those in group B(all P＜0.001),and signal intensity(SI)metastases in group A was higher than those in group B and C(both P＜0.05).No significant difference of subjective score and SNR was found between groups A and C,nor of SImetastases between groups B and C(all P＞0.05).Totally 102 skull metastases were diagnosed with PET/CT or BS,while 129,151 and 115 lesions were detected in group A,B and C,respectively,with accuracy rate of 79.07%(102/129),67.55%(102/151)and 88.70%(102/115),respectively.Conclusion MATRIX CE-T1 FLAIR sequence could be used to detect skull metastases.

OBJECTIVE To understand the drug resistance among the acquired immune deficiency syndrome(AIDS)population who failed in the antiviral therapy from 2022 to 2023 and analyze the molecular network.METHODS The plasma specimens were collected from the population with viral load no less than 1000 cps/ml who received antiviral therapy for more than 6 months in Aksu area from 2022 to 2023,which were delivered to Aksu Regional Center for Disease Control and Prevention for test.MEGA5 and the Stanford University drug resistance database were employed to determine the subtypes and drug resistance after the sequences of human immunodefi-ciency virus type Ⅰ polymerase gene region(HIV-1pol)were obtained,and the molecular network was established by HIV-trace.RESULTS Totally 648 sequences of HIV-1pol region were obtained,CRF07_BC(97.69％)was the major subtype,and the drug resistance rate was 58.33％;the drug resistance rates to non-nucleoside reverse transcriptase inhibitor(NNRTI),nucleoside reverse transcriptase inhibitor(NRTI)and protease inhibitor(PI)were 51.70％,19.75％and8.64％,respectively.The univariate analysis showed that year(x2=6.341),age(x2=18.455)and route of infection(x2=14.061)had remarkable effects on the drug resistance among the population with failed ART(P＜0.05).Multivariate regression analysis indicated that the drug resistance rate was higher in 2022 than in 2023(95％CI:1.132 to 2.191),and the drug resistance rate was higher among the population aged less than 60 years old than among the population more than 6 years old(95％CI:3.647 to 70.268,95％CI:1.435 to 8.235,95％CI:1.061 to 6.164,re-spectively).With 1.5％of the genetic distance set as the threshold,the molecular network was established,the network access rate was 49.07％,77.14％of the clusters had drug-resistant mutation sites,and the male population was at higher risk of network access than the female population.CONCLUSIONS The drug resistance rate is relatively high among the AIDS population with failed ART,and the drug-resistant strains appear in clusters in the molecular network.It is neces-sary to further strengthen the monitoring of drug resistance and improve the quality of the follow-up so as to reduce the occurrence of drug resistance and transmission of virulent strains.

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 explore the application value of serum heat shock protein 90α(Hsp90α)combined with β2-microglobulin(β2-MG)detection in the early diagnosis and prognosis of colorectal cancer(CRC).Methods A total of 101 patients with CRC who received their first treatment were selected as the CRC group(no surgery,radiotherapy or chemotherapy before enrollment),100 patients with benign colon tumor admitted to our hospital during the same period were selected as the benign tumor group and 94 healthy individuals who underwent physical examinations in our hospital were used as the control group.The levels of serum Hsp90α and β2-MG in all subjects were detected by ELISA.Follow-up was conducted every three months within the first two years after surgery,and every six months in the third year,for a total follow-up period of 3 years,and the survival status of CRC patients within 3 years was recorded.ROC curve analysis was used to evaluate the diagnostic value of serum Hsp90α and β2-MG for CRC.The Kaplan-Meier method was used to draw the survival curves of CRC patients with different expression levels of Hsp90α and β2-MG.Results The serum levels of Hsp90α and β2-MG increased successively in the control group,the benign tumor group and the CRC group(P＜0.05).There were no significant differences in serum levels of Hsp90α and β2-MG between CRC patients of different genders,ages and lesion locations.The levels of serum Hsp90α and β2-MG in patients with tumor diameter＞5 cm,low differentiation degree,TNM stage Ⅲ and lymph node metastasis were higher than those in patients with tumor diameter≤5 cm,moderate to high differentiation degree,TNM stage Ⅰ-Ⅱ and no lymph node metastasis(P＜0.05).The ROC results showed that the combined diagnostic efficacy of serum Hsp90α and β2-MG was superior to that of serum Hsp90α or β2-MG alone(Z=2.433,2.435,P＜0.05).Based on the average expression levels of serum Hsp90α and β2-MG in CRC patients(76.66 μg/L and 6.52 μg/L),patients were divided into the high expression group of Hsp90α(59 cases),the low expression group of Hsp90α(42 cases),the high expression group of β2-MG(63 cases)and the low expression group of β2-MG(38 cases).Among the 101 CRC patients,31 died and 70 survived,with a total survival rate of 69.31％.The Kaplan-Meier survival curve showed that the 3-year survival rates of patients with high expression levels of Hsp90α and β2-MG were lower than theose of patients with low expression levels of Hsp90α and β2-MG(P＜0.01).Conclusion The expression levels of serum Hsp90α and β2-MG are both elevated in CRC patients,and they are closely related to the occurrence,development and prognosis of CRC.

Objective To explore the application value of serum heat shock protein 90α(Hsp90α)combined with β2-microglobulin(β2-MG)detection in the early diagnosis and prognosis of colorectal cancer(CRC).Methods A total of 101 patients with CRC who received their first treatment were selected as the CRC group(no surgery,radiotherapy or chemotherapy before enrollment),100 patients with benign colon tumor admitted to our hospital during the same period were selected as the benign tumor group and 94 healthy individuals who underwent physical examinations in our hospital were used as the control group.The levels of serum Hsp90α and β2-MG in all subjects were detected by ELISA.Follow-up was conducted every three months within the first two years after surgery,and every six months in the third year,for a total follow-up period of 3 years,and the survival status of CRC patients within 3 years was recorded.ROC curve analysis was used to evaluate the diagnostic value of serum Hsp90α and β2-MG for CRC.The Kaplan-Meier method was used to draw the survival curves of CRC patients with different expression levels of Hsp90α and β2-MG.Results The serum levels of Hsp90α and β2-MG increased successively in the control group,the benign tumor group and the CRC group(P＜0.05).There were no significant differences in serum levels of Hsp90α and β2-MG between CRC patients of different genders,ages and lesion locations.The levels of serum Hsp90α and β2-MG in patients with tumor diameter＞5 cm,low differentiation degree,TNM stage Ⅲ and lymph node metastasis were higher than those in patients with tumor diameter≤5 cm,moderate to high differentiation degree,TNM stage Ⅰ-Ⅱ and no lymph node metastasis(P＜0.05).The ROC results showed that the combined diagnostic efficacy of serum Hsp90α and β2-MG was superior to that of serum Hsp90α or β2-MG alone(Z=2.433,2.435,P＜0.05).Based on the average expression levels of serum Hsp90α and β2-MG in CRC patients(76.66 μg/L and 6.52 μg/L),patients were divided into the high expression group of Hsp90α(59 cases),the low expression group of Hsp90α(42 cases),the high expression group of β2-MG(63 cases)and the low expression group of β2-MG(38 cases).Among the 101 CRC patients,31 died and 70 survived,with a total survival rate of 69.31％.The Kaplan-Meier survival curve showed that the 3-year survival rates of patients with high expression levels of Hsp90α and β2-MG were lower than theose of patients with low expression levels of Hsp90α and β2-MG(P＜0.01).Conclusion The expression levels of serum Hsp90α and β2-MG are both elevated in CRC patients,and they are closely related to the occurrence,development and prognosis of CRC.

Objective:To analyze the influencing factors of mood state of common rheumatic (rheumatoid arthritis; systemic lupus erythematosus; ankylosing spondylitis) patients and find out the common characteristics of patients with negative emotions, so as to identify and treat rheumatic patients with anxiety and depression in clinical practice.Methods:A total of 205 patients with rheumatism (83 with rheumatoid arthritis, 74 with systemic lupus erythematosus, 48 with ankylosing spondylitis) admitted to the Shandong Provincial Hospital Affiliated to Shandong University from April to May 2023 were included. The general condition and POMS of patients were collected. All patients were divided into 3 groups of low-TMD/ middle-TMD/ high-TMD(TMD≤90 scores; 90 scores105 scores). The χ2 test was used for categorical variables, and the continuous variables were tested for normal distribution. If they followed a normal distribution, the independent sample t test (for homogeneous variance) or the Welch′s t test (for unequal variance) was used for comparison between the two groups, and one-way analysis of variance was used for comparison between multiple groups; if they did not follow a normal distribution, the Kruskal-Wallis H test was used for comparison between groups. Patients with TMD>90 scores were defined as the negative emotion group. Gender, age, education level, economic income status, and TMD were included in the two-step cluster analysis (TCA) to obtain three cluster groups and analyze the differences between the groups. Logistic regression was used to analyze the risk factors. Results:The study found that patients with rheumatic diseases with low serum albumin levels ( F=6.26, P=0.003), low education level ( χ2=8.36, P=0.015), low economic level ( χ2=15.59, P<0.001), short disease course ( H=28.01, P<0.001), and high disease activity ( χ2=56.93, P<0.001) had higher TMD scores, which was not related to the type of disease ( χ2=4.81, P=0.090). The negative mood group had a higher proportion of females (57.6% vs. 73.4%, χ2=5.16, P=0.023), a shorter course of disease [24(12, 48) months vs. 48(24, 93) months, Z=13.58, P<0.001], and a lower serum albumin [(42.2±4.0) g/L vs. (44.0±3.4)g/L, t=-14.09, P=0.002], low level of education ( χ2=9.04, P=0.029), low level of income ( χ2=10.29, P=0.036), high disease activity ( χ2=61.91, P<0.001). The results of cluster analysis indicated that the above factors were significantly different among the three cluster groups except the course of disease. It is noteworthy that age ( F=19.25, P<0.001) and serum albumin ( F=5.64, P=0.004) had the lowest value and the highest TMD score ( F=5.64, P<0.001). Regression analysis showed that gender, disease course and disease activity were related factors to the occurrence of negative emotions, and high disease activity was a risk factor [ OR(95% CI) =26.58(4.53, 156.09), P<0.001]. Men [ OR(95% CI)=0.20 (0.08, 0.50), P=0.001) and the course of [ OR(95% CI)=0.99 (0.98, 1.00), P=0.007) as the protective factors. Conclusion:Male, serum albumin level, education level, income level, disease course and disease activity were the main factors affecting the mood state of patients with rheumatism, in which high disease activity was the risk factor, male and long disease course were the protective factors.

Objective To investigate risk factors for residual lesions after initial transurethral resection of bladder tumors(TURBT)and risk factors for tumor recurrence after second TURBT in patients with non-muscle-invasive bladder cancer(NMIBC)in order to provide reference for clinical management.Methods A case-control study design was adopted to include 120 NMIBC patients who underwent initial TURBT and then second surgery within 2～8 weeks in our department from January 2017 to January 2025.Based on the presence of residual lesions after the initial TURBT or not,the patients were divided into a residual lesion group(n=34)and a non-residual lesion group(n=86).Chi-square test and multivariate logistic regression analysis were performed to identify potential risk factors for residual lesions following the initial TURBT.Univariate and multivariate Cox regression models were used to analyze potential risk factors for tumor recurrence after the second TURBT.Results The residual lesion rate after initial TURBT was 28.33％.Chi-square test analysis revealed that tumor stage T1(Chi-square=5.756,P=0.016)and broad tumor base(Chi-square=4.331,P=0.037)were factors influencing residual lesions after initial TURBT.Multivariate logistic regression analysis identified tumor stage T1(OR=3.047,95％CI:1.128～8.226,P=0.028)as an independent risk factor for residual lesions after initial TURBT.The tumor recurrence rate after second TURBT was 17.5％.Multivariate Cox regression analysis identified tumor stage T1(OR=4.258,95％CI:1.248～14.532,P=0.021),intravesical chemotherapy instillation after second TURBT(OR=3.539,95％CI:1.284～9.752,P=0.015),history of urinary system tumors(OR=3.002,95％CI:1.145～7.873,P=0.025)and high platelet-to-lymphocyte(PLR)ratio(OR=2.798,95％CI:1.115～7.023,P=0.028)as independent risk factors for tumor recurrence after second TURBT.Conclusion Tumor stage T1 and broad tumor base are risk factors for residual lesions after initial TURBT,while tumor stage T1,intravesical chemotherapy instillation after second TURBT,history of urinary system tumors and high PLR ratio are risk factors for tumor recurrence after second TURBT.Comprehensive analysis on above 4 indicators can effectively assess the risk of tumor recurrence in NMIBC patients following second TURBT,and timely early medical intervention is beneficial for improving patient outcomes.

Objective:To explore the effect of combining intermittent θ pulse stimulation (iTBS) of the cerebellum with lower extremity exoskeleton robot support on the balance and walking function of stroke survivors.Methods:Seventy-five stroke survivors complicated with lower extremity dysfunction were divided into an iTBS group, an exoskeleton group and a combined group, each of 25, according to a random number table. In addition to conventional rehabilitation training, the iTBS group was given cerebellar iTBS combined with traditional walking training, the exoskeleton group received sham cerebellar iTBS combined with walking training assisted by a lower extremity exoskeleton robot. The combined group received both therapies. The schedule was once a day, 5 days a week for 3 weeks. Before and after the treatment, the 10-metre walking test (10MWT), the Berg Balance Scale (BBS) and the Fugl-Meyer lower extremity assessment (FMA-LE) were used to evaluate the subjects′ walking ability, balance and lower extremity motor ability. Gait and neuro-electrophysiological tests were also conducted in all three groups.Results:After the treatment, a significant improvement was observed in the 10MWT times, BBS scores, FMA-LE scores, stride frequency and stride speed of all three groups compared with before the treatment. On average, the results of the exoskeleton and combined groups were significantly better than those of the iTBS group, and those of the combined group were significantly better than among the exoskeleton group. Almost everyone′s MEP latency and amplitude had improved significantly compared with before the treatment, but the improvements in the exoskeleton group tended to be superior to those in the iTBS group ( P≤0.05). The latency in the combined group averaged (21.25±1.70)ms, and the amplitude averaged (184.17±6.54)μV, both significantly better than the exoskeleton group′s averages. Conclusions:Cerebellum iTBS combined with lower extremity exoskeleton walker training can significantly improve the motor functioning, balance and walking ability of stroke survivors.