Objective : To explore the effect of Wilms′ tumor 1-associated protein(WTAP) on tissue collagen deposition in pulmonary fibrosis caused by bleomycin. Methods : 60 mice were randomly divided into four groups: control group(Control group), Bleomycin-induced pulmonary fibrosis group(BLM group), pulmonary fibrosis lentivirus empty vector control group(BLM+LV-NC group), pulmonary fibrosis WTAP lentivirus group virus group(BLM+LV-WTAP group). Experimental pulmonary fibrosis mouse model was established by subcutaneous injection of bleomycin(35 mg/kg) into the abdomen, twice a week for a total of 8 times. After modeling, Western Blot was used to detect the protein expression of fibrosis-related markers α-smooth muscle actin(α-SMA), type I collagen(Collagen Ⅰ), fibronectin(Fibronectin), and WTAP protein. Masson staining and Sirius Red staining were used to detect collagen deposition. RT-qPCR was used to detect WTAP mRNA expression, WTAP lentivirus infection effect, and Collagen Ⅰ mRNA expression. Results: Compared with the Control group, the expression of pulmonary fibrosis markers α-SMA(P<0.001), Collagen Ⅰ(P<0.001), and Fibronectin(P<0.01) protein in the BLM group all increased. Masson staining(P<0.001) and Sirius Red staining(P<0.001) confirmed that significant collagen deposition occurred in the lung tissue of the BLM group. In addition, the expression of WTAP protein in the lung tissue of the BLM group increased(P<0.01). Compared with the Control group, the expression of WTAP mRNA in the BLM group increased(P<0.001). Compared with the BLM+LV-NC group, the expression of WTAP mRNA in the tissues of the BLM+LV-WTAP group decreased(P<0.001), proving that virus infection is effective. After infection with WTAP lentivirus, collagen fiber deposition decreased(P<0.001), Collagen Ⅰ mRNA(P<0.001) level decreased, and protein(P<0.001) expression decreased in the BLM+LV-WTAP group. Conclusion Knocking down of WTAP can reduce collagen deposition in bleomycin-induced pulmonary fibrosis tissue in mice and improve experimental pulmonary fibrosis.

Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease that can lead to the damage of multiple tissues and organs throughout the body.Stimulator of interferon genes(STING)is an endoplasmic reticulum membrane protein that acts as an indirect cytoplasmic DNA sensor.The activation of the STING signaling pathway may be involved in T2DM and its microvascular complications through various mechanisms.This article reviews the research progress in the mechanism of STING in T2DM and its microvascular complications.

Objective:To investigate the correlation between liver stiffness and histopathological changes in a rat model of acute hepatitis using virtual touch tissue imaging quantification (VTIQ) technology.Methods:A total of 100 SPF-grade SD rats were randomly divided into 3 groups: control ( n=30), low-dose ( n=35), and high-dose ( n=35) groups. Acute hepatitis models were induced in the low-dose and high-dose groups using 400 mg/kg and 600 mg/kg of Thioacetamide (TAA), respectively. Liver stiffness parameters of the right median lobe and right lobe were measured using VTIQ technology, Mean-H and Mean-L represent the liver lobes with higher and lower liver stiffness measurments, respectively, while Mean represent the average of the measurements from both liver lobes. Comparative analyses of liver stiffness parameters were performed across three groups and between the two lobes of the liver. The correlations between the Mean values of liver stiffness and semi-quantitative histopathological data were investigated. Ten rats were randomly selected from each of the 3 groups to test the repeatability of VTIQ values before and after euthanasia with intraperitoneal anesthesia. Subsequently, 10 rats after euthanasia from each 3 group were randomly chosen to assess the repeatability of VTIQ measurements for inter-observer and intra-observer variabilities. Results:VTIQ results showed statistically significant differences in Mean, Mean-H, and Mean-L among the 3 groups (all P<0.01). The high-dose group had higher measurements compared to the low-dose and control groups, with significant intergroup differences (all P<0.01). Significant differences in Mean-H and Mean-L were observed between the two liver lobes in both low and high-dose groups (all P<0.01). The Mean value showed significant positive correlations with semi-quantitative histopathological data of hepatocellular edema, periportal inflammatory cell infiltration, macrophage proliferation, and bile duct proliferation ( r=0.391, 0.648, 0.577, 0.542; all P<0.01). Multivariate linear regression analysis indicated that hepatocellular edema, eosinophilic change, and bile duct proliferation significantly and positively predicted the Mean value (β=-0.278, -0.196, -0.333; all P<0.05). There were no significant differences of VTIQ measurements befor and after euthanasia (all P>0.05), with repeatability coefficients of 0.166, 0.182, 0.185 for Mean, Mean-H, and Mean-L, respectively. Post-euthanasia, inter- and intra-observer VTIQ differences remained non-significant (all P>0.05), with Mean, Mean-H, Mean-L coefficients of 0.114, 0.194, 0.165 and 0.206, 0.322, 0.268, respectively. Conclusions:VTIQ technology demonstrates potential clinical value in assessing a rat model of acute hepatitis, offering a new perspective for non-invasive evaluation of acute hepatitis. However, its clinical application requires further validation.

Objective To evaluate both the causal relationship between plasma metabolites and the risk of knee osteoarthritis(KOA)and the potential mediating or masking effect of immune cells using Mendelian randomization(MR)systems.Methods The GWAS data on 1400 plasma metabolites,731 immune cell traits and KOA was retrieved from the genome-wide association study(GWAS)database.Two-way MR analysis was used to evaluate the causal relationship between plasma metabolism and KOA.Two-step mediation MR analysis was conducted to evaluate immune cell traits that might have mediating or masking effects.Results After sensitivity analysis and screening,65 plasma metabolites and 35 immune cell traits were found to have causal relationships with KOA(P＜0.05).Mediation analysis found that CD45RA+CD28-CD8br％CD8br had a mediating effect in the causal relationship between three metabolites(2-hydroxyhi-ppurate,X-07765,X-23739)and the risk of KOA.2-hydroxyhippurate(salicylic acid)exerted a masking effect,and the effect ratio was 0.0412.Conclusion A variety of plasma metabolites and immune cell traits are causally related to KOA,which should not be regarded as a simple degenerative joint disease.The protective effect of salicylic acid against KOA may be weakened by its role in inducing the differentiation of Treg cells,which is worthy of more studies.

Articular cartilage superficial zone (SFZ) is the top layer of articular cartilage and its injuries are common in clinic.Therefore its find in time and conducting the treatment can delay the progress rate of os-teoarthritis (OA) and alleviate the pain and economic burden of the patients.At present,MRI is the most sen-sitive noninvasive examination technique to evaluate articular cartilage injury.Conventional MRI is limited in the early detection of subtle degeneration before cartilage morphological changes existence,and articular carti-lage lesions can only be detected when the injury is in an irreversible stage.In recent years,with the develop-ment of high field intensity MRI techniques such as 3T and 7T,the detection of water molecules,collagen fi-bers and tissue anisotropy in cartilage has considerable advantages,which can make the quantitative analysis and functional imaging for the ultrastructure and biochemical composition changes of SFZ in articular carti-lage.This article reviews the latest research progress on diagnostic value of MRI on articular cartilage SFZ and injuries.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective:To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy.Methods:A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n=47) and non-transplantation group (NTG; n=121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ2 test, Kaplan-Meier method and independent sample t-test. Results:Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG ( χ2=5.71, P=0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG ( χ2=4.32, P=0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P<0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t=-2.15, P=0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P>0.05). Conclusion:Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.

Objective:To explore the impact of tissue inhomogeneity correction on the accuracy of dose calculations in brachytherapy of cervical carcinoma by comparing the results of Monte Carlo (MC) dose simulation with those (TG43 algorithm) of treatment planning system (TPS).Methods:Firstly, the 192Ir source was modeled by using a MC code specially designed for brachytherapy, called egs_brachy. The accuracy of this model was verified by comparing it with the published data. Then, 8 brachytherapy plans of cervical carcinoma were selected which completed treatment at Sun Yat-sen University Cancer Center from January 2022 to May 2023, and their CT image data and treatment parameters were exported. Relevant plan information such as the source dwell positions and their corresponding dwell times were reconstructed on the patient's individualized CT images using a self-developed program. The MC dose distributions were calculated for each case and compared with the TPS calculations. When the anterior wall of the rectum was filled with gas, the differences between MC simulation and TPS calculation were compared. Additionally, 5 different calculation ranges were set for MC simulation, and the MC simulation results of different calculation ranges were compared with the TPS's, combining with the time of MC simulation, a reasonable MC calculation range was comfirmed. Then, the scipy.stats library of Python was utilized to perform independent sample t-test on dosimetric comparison results, including D 90% of high risk clinical target volume (HR-CTV) and D max, D mean, and D 2 cm3 of organs at risk (OAR). Results:The comparison between MC calculations and TPS results showed that the CTV's D 90%, the bladder's D mean and the small intestine's D mean were all within ± 1%, except for the D max difference of approximately 3% on the anterior wall of the rectum. The 2%/2 mm gamma pass rates were all>98%. When anterior wall of the rectum filled with gas, compared with MC, TPS overestimated the anterior wall of the rectum's D 2 cm3 and D mean by approximately 6.06% ( t=-6.80, P=0.002) and 5.35% ( t=-6.57, P=0.003), respectively. When the dose calculation range of MC was consistent with that of TPS, the MC calculation result underestimated the dose distribution in water by approximately 4%. When extending the MC dose calculation range by 2 cm beyond the TPS calculation range, the dose difference between MC and TPS in homogeneous water was approximately 1%, and the calculation time was saved by at least 8 h compared to MC dose calculation based on the whole CT. Conclusion:The existing TPS TG43 algorithm can ensure that the dose calculation of cervical carcinoma meets the basic accuracy requirements of clinical practice, but tissue inhomogeneity correction is recommended to improve the accuracy of dose calculation whenever possible.

Objective:To explore the alterations in functional connectivity density (FCD) resulted from mild cognitive impairment (MCI) and their correlations with cognitive scores in various cognitive domains in patients with Parkinson's disease (PD).Methods:Forty-three PD patients admitted to Department of Neurology, Sixth Affiliated Hospital of Nantong University from January 2022 to April 2024 were selected and divided into PD-MCI group (MoCA scores<26) and PD with normal cognition (PD-NC) group (MoCA scores≥26) according to Montreal Cognitive Assessment (MoCA). Another 23 middle-aged and elderly healthy volunteers (HC group) matched with PD patients in age, gender and education level were recruited at the same period. Resting-state functional MRI (rs-fMRI) data were collected and whole brain FCD was calculated. Differences of clinical data, whole brain FCD, and FCD in brain regions with significantly different FCD among the 3 groups were compared. Efficiency of FCD in brain regions with significantly different FCD between PD-MCI group and PD-NC group in differentially diagnosing PD-MCI and PD-NC was analyzed by receiver operating characteristic (ROC) curve. Pearson correlation was used to the analyze the correlations of FCD in brain regions with significantly different FCD with MoCA score and cognitive scores in various cognitive domains.Results:Among the 43 patients, 23 were into the PD-MCI group and 20 into the PD-NC group. PD-MCI group had significantly lower scores in the visuospatial and executive function, abstraction, and delayed memory cognitive domains than PD-NC group ( P<0.05). Brain regions with significantly different FCD among the 3 groups were the right parahippocampal gyrus, left gyrus rectus, right rolandic operculum, left middle occipital gyrus, right precentral gyrus, left middle frontal gyrus, and left medial superior frontal gyrus. Compared with the HC group, the PD-MCI group and PD-NC group had significantly increased FCD at the right parahippocampal gyrus, left gyrus rectus and right rolandic operculum, statistically decreased FCD at the right precentral gyrus, left middle frontal gyrus, and left medial superior frontal gyrus ( P<0.05). Compared with the HC group, the PD-MCI group had significantly increased FCD at the left middle occipital gyrus ( P<0.05). Compared with the PD-NC group, the PD-MCI group had significantly decreased FCD at the right parahippocampal gyrus, and statistically increased FCD at the left middle occipital gyrus and left middle frontal gyrus ( P<0.05). Area under ROC curve (AUC) of FCD in brain regions with significantly different FCD in discriminating PD-MCI and PD-NC was 0.878, with sensitivity of 90.0% and specificity of 91.3%. FCD at right parahippocampal gyrus, left middle occipital gyrus and left middle frontal gyrus was negatively correlated with MoCA score ( P<0.05); FCD at right parahippocampal gyrus was positively correlated with cognitive scores in the visuospatial and executive function, and delayed memory domains ( P<0.05); FCD at left middle occipital gyrus was negatively correlated with cognitive scores in the executive function and visual-spatial skills, and abstraction domains ( P<0.05); FCD at the left medial frontal gyrus was negatively correlated with cognitive scores in the visuospatial and executive function, abstraction and delayed memory domains ( P<0.05). Conclusions:Abnormal FCD can be noted in some brain regions of PD patients, enjoying differences between PD-MCI patients and PD-NC patients. Combined FCD in brain regions with significantly different FCD has high value in differentially diagnosing PD-MCI and PD-NC, and FCD in brain regions with significantly different FCD is correlated with cognitive function changes in PD patients.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.