AIM:To investigate the role of serum high-sensitivity C-reactive protein(hsCRP)in the pathogenesis and progression of diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM).METHODS:A nested case-control study was conducted involving 187 T2DM patients(187 eyes)who attended at Eye Center, Beijing Tongren Hospital, Capital Medical University from June 2017 to October 2024. Patients were categorized into three groups: the diabetes mellitus(DM)group, non-proliferative DR(NPDR)group, and proliferative DR(PDR)group. Baseline information was collected, including age, sex, duration of DM, and duration of hypertension. All patients underwent fasting biochemical tests and comprehensive ophthalmic examinations.RESULTS: A positive correlation was observed between hsCRP and fasting blood glucose(FBG; P=0.004)and glycated hemoglobin A1c(HbA1c; P=0.048)by Spearman's rank correlation coefficient analysis. After adjusting for confounding factors, multivariable Logistic regression identified hsCRP as a significant risk factor for DR(OR=2.67, 95% CI: 1.19-5.96, P=0.017). CONCLUSION:Serum hsCRP is positively correlated with FBG and HbA1c and can serve as an important predictor of the severity of DR.

Objective: To provide the mechanism-based pharmacotherapy of the Huatan Qushi formula (HTQS formula), for the health management and treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A rat model of NAFLD was employed to examine the efficacy and safety of the HTQS formula. In vivo active components and potential mechanisms of the HTQS formula were identified using UPLC‒MS/MS combined with network pharmacology. The influence of the HTQS formula on the dominating proteins in PI3K/Akt pathway was validated in vivo using western blot. Finally, 16S rRNA sequencing of the gut microbiome was conducted followed by targeted metabolomics detecting fecal short-chain fatty acids (SCFAs) and bile acids to determine the impact of the HTQS formula on gut microbiota. Results: The HTQS formula reduced weight gain and hepatic steatosis in NAFLD rats and decreased serum total cholesterol (TC), triglycerides, blood glucose, and insulin resistance (IR) without causing liver or kidney injury. We detected 28 components using UPLC‒MS/MS and identified 439 shared targets between NAFLD and the HTQS formula. Primarily, we focused on the PI3K/Akt signaling pathway based on protein‒protein interaction network analysis. We validated that the HTQS formula inhibited liver steatosis and inflammation by increasing the phosphorylation levels of PI3K, AKT, P27, GSK3β in the PI3K/Akt signaling pathway. 16S rRNA sequencing revealed that the HTQS formula reduced the abundance of the genus Family_XIII_AD3011_group, which was positively correlated with IR and taurodeoxycholic acid. In addition, Lachnospiraceae_UCG_010 inversely correlated with TC and five bile acids, which could be essential to the therapeutic effect of the HTQS formula against NAFLD. Conclusions The HTQS formula proved to be an effective pharmacotherapy for NAFLD without causing liver or kidney injury. Multiple potent components of the HTQS formula could alleviate liver steatosis and lipid metabolism disorder by modulating the PI3K/Akt signaling pathway and restoring gut microbiota composition.

Objective:To explore the evaluation value of serum levels of positive pentameric protein 3 (PTX3) and creatine kinase isoenzyme MB (CK-MB) on volume load in patients with chronic decompensated heart failure (CDHF).Methods:A total of 300 CDHF patients who visited the Xingtai Central Hospital from July 2019 to July 2022 were selected and divided into a capacity overload group ( n=182) and a non capacity overload group ( n=118) based on their capacity balance level. Two clinical data sets were compared and analyzed. The receiver operating characteristic (ROC) curve was used to analyze the evaluation value of serum PTX3 and CK-MB levels on the volume load of CDHF patients. The clinical disease characteristics of the two groups of patients were analyzed using univariate analysis, and the influencing factors of volume load of CDHF patients were analyzed using logistic regression. A column chart model was constructed and validated. Results:The body mass index (BMI), waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose (FBG), glycosylated hemoglobin (HbA 1c), C-reactive protein (CRP), uric acid (UA), homeostasis model assessment of insulin resistance (HOMA-IR) of patients in the capacity overload group were higher than those in the non-capacity overload group, and the differences were statistically significant (all P<0.05). The PTX3, CK-MB, pulmonary capillary wedge pressure (PCWP), and CVP levels of patients in the capacity overload group were higher than those in the non-capacity overload group, while albumin, hemoglobin, and hematocrit were lower than those in the non-capacity overload group, and the differences were statistically significant (all P<0.05). The ROC curve showed that the area under the curve (AUC) of PTX3 and CK-MB for predicting capacity overload in CDHF patients are 0.795 and 0.718, with sensitivity of 86.2% and 83.7%, specificity of 65.4% and 68.6%, respectively, indicating high predictive accuracy; The AUC of the two joint predictions is 0.817, the sensitivity was 92.5%, and the specificity was 70.6%. The prediction accuracy was higher than PTX3 ( Z=3.812, P<0.05) and CK-MB ( Z=3.365, P<0.05). PTX3, CK-MB, albumin, hemoglobin, hematocrit, PCWP, and central venous pressure (CVP) were all influencing factors of volume load status in CDHF patients (all P<0.05). The column chart risk prediction model established based on these factors had high accuracy and strong applicability in clinical treatment. Conclusions:Serum PTX3 and CK-MB levels are influencing factors for volume overload in CDHF patients. A column chart model constructed in combination with indicators such as albumin, hemoglobin, hematocrit, PCWP, and CVP has high predictive value for the volume overload status of CDHF.

Objective:To evaluate the accuracy of the optical surface imaging system (OSI) using stereotactic radiosurgery (SRS) algorithm in single-center non-coplanar treatment of multiple brain metastases.Methods:Data of phantom and 15 patients with multiple brain metastases who underwent single-center non-coplanar radiotherapy in West China Hospital of Sichuan University from February to April 2022 were retrospectively analyzed. kV/MV and OSI imaging were used for imaging of the patients and phantoms under the same non-coplanar couch angle, respectively. The accuracy of OSI imaging of the phantoms and patients was evaluated using kV/MV imaging as reference image. The difference between the OSI and kV/MV systems is defined as accuracy, and the percentage of the absolute difference ≤1.00 mm in the translational direction or ≤0.50° in the rotational direction is defined as the threshold pass rate. Origin software was used to draw radar maps and Bland-Altman plots for statistical analysis.Results:When OSI images were used for the phantom imaging, the average differences in six-dimensional directions of lateral, long, vertical, rotational, roll and pitch were 0.03 mm, -0.09 mm, -0.27 mm, 0.04°, 0.17° and -0.19°, respectively. The maximum values were -2.20 mm, -2.30 mm, -1.20 mm, 0.60°, -1.00°, and -1.00°, respectively. When OSI system was utilized for the imaging of 15 patients, the average differences in six-dimensional directions were 0.44 mm, 0.16 mm, -0.20 mm, -0.11°, 0.10°, and -0.12°, respectively. The maximum values were -1.80 mm, 2.00 mm, 0.90 mm, -0.90°, -0.70°, and 0.80°, respectively. The translational errors mainly occurred in the lateral and long directions. The qualified rates of the threshold values of the phantoms and patients were 77% and 75% in the lateral direction, 82% and 89% in the long direction, respectively. In addition, 57% and 56% of patients met the threshold conditions of ±1.00 mm and ±0.50° in the six-dimensional directions, respectively.Conclusions:The OSI system using new SRS algorithm cannot meet the high accuracy requirements of single-center non-coplanar radiotherapy for multiple brain metastasis, especially in the lateral and long directions. It is not recommended for non-coplanar image guidance.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Objective:To clone the Helicobacter pylori(Hp)hp0169 gene and conduct the crystallographic study,and to clarify its secondary and tertiary structures.Methods:The hp0169 gene and its encoded protein sequence of the Hp NCTC26695 strain were retrieved from the UniProt database.Bioinformatics method was used to analyze the physicochemical properties of the Hp recombinant protease(HpPrtC)protein;SOPMA and DNAStrar softwares were used to predict the secondary structure characteristics of HpPrtC protein;SWISS-MODEL software was used to construct the tertiary structure of the HpPrtC protein;IEDB and ABCpred softwares were used to predict the antigenic epitopes of the B lymphocytes HpPrtC protein;SYFPEITMI website was used to predict the antigenic epitopes of the T lymphocytes of HpPrtC protein;the expert pool(EP)and random forest(RF)algorithms were used to predict the crystallizability of the HpPrtC protein;the HpPrtC recombinant protein was expressed in the prokaryotic system;the HpPrtC recombinant protein was purified by Ni2+affinity chromatography and size-exclusion chromatography;the crystallization conditions for HpPrtC were screened by crystallization kit.Results:The hp0169 gene contained 1 269 base pairs and encoded the protein of 422 amino acids,the theoretical isoelectric point was 7.64 and the relative molecular weight was 47 300.HpPrtC was a hydrophilic and soluble protein.The number of amino acids of alpha helices of HpPrtC accounted for 35.78%,beta sheets 18.72%,beta turns 6.87%,and random coils 38.63%.The antigen epitope analysis results showed that HpPrtC contained five dominant linear epitopes of B lymphocytes,three conformational epitopes,and multiple potential dominant epitopes of T lymphocytes.The homology modeling results showed that HpPrtC formed a dimer,and each monomer displayed a barrel structure surrounded by β sheets,alpha helices,and random coils.HpPrtC was predicted to have moderate crystallizability without signal peptides and transmembrane helices.Small clustered needle-like crystals of HpPrtC were obtained under the conditions of 0.2 mol·L-1 magnesium chloride,0.1 mol·L-1 tris(hydroxymethyl)amino methane(Tris),3.4 mol·L-1 hexanediol,and pH=8.5.Conclusion:HpPrtC is a hydrophilic protein that forms a dimeric structure and crystallizes into small clustered needle-like crystals under suitable conditions.HpPrtC contains dominant antigenic epitopes of the T lymphocytes and B lymphocytes and can serve as an antigen for the design of Hp vaccines to establish the multivalent fusion vaccines or multi-epitope vaccines;the results provide an experimental basis for the prevention and control of Hp.

Objective:To explore the relationship between relapse tendency and psychological craving in fe-male methamphetamine(MA)-dependent young adults,focusing on the roles of self-control and future time per-spective.Methods:A total of 340 MA-dependent young adults from two women's compulsory isolation drug reha-bilitation centers in Sichuan Province were included.Participants were assessed with the Relapse Tendency Ques-tionnaire(RTQ),Obsessive Compulsive Drug Use Scale(OCDUS),Drug Abuser Self-Control Ability Question-naire(DASAQ)and General Future Time Perspective Scale(GFTPQ).The moderated mediation model was ana-lyzed by using the SPSS macro program PROCESS(version4.2).Results:The RTQ scores were positively correla-ted with the OCDUS scores(r=0.45,P＜0.001).The DASAQ scores partially mediated the relationship between the scores of OCDUS and RTQ,accounted for 37.91％of the total effect.The GFTP scores moderated the relation-ship between the scores of the OCDUS,DASAQ and RTQ(β=-0.18,0.19,P＜0.001).Conclusion:The influ-ence of psychological craving on relapse tendency in female MA-dependent young adults exhibits a moderated me-diating effect,suggesting the potential of enhancing self-control and future time perspective for preventing relapse and improving detoxification efficiency.

Objective:To analyze the clinical features and magnetic resonance imaging of non-malignant patients assigned to Prostate Imaging Reporting And Data System (PI-RADS) 5 score.Methods:We performed a retrospective review of 289 patients who underwent magnetic resonance ultrasound targeted combined system biopsy with PI-RADS 5 lesions in the First Affiliated Hospital of Nanjing Medical University between May 2019 and July 2021. The median age 72 (66, 77)years, median body mass index 24.4(22.3, 27.1)kg/m 2, median prostate volume (PV) 37.39(29.39, 48.86) ml, median PSA 22.24(10.91, 62.69) ng/ml, and median PSAD 0.53(0.30, 1.52)ng/ml 2 were recorded. According to the biopsy pathological results, all patients were divided into benign lesion group and prostate cancer group. PSA, PSAD, PV, and apparent diffusion coefficient (ADC) values were compared, and magnetic resonance imaging and clinical characteristics of patients with biopsy benign lesions were analyzed. Results:There were 11 cases (3.8%) with benign lesion and 278 cases (96.2%) with prostate cancer. The characters of 11 negative biopsy cases were displayed as follows: median age 69(66, 79)years, median body mass index 22.0(21.0, 25.5)kg/m 2, median PV 62.90(38.48, 71.96)ml, median PSA 5.55(2.99, 20.52)ng/ml, median PSAD 0.16(0.07, 0.24) ng/ml 2, median ADC 714.47(701.91, 801.26)×10 -6 mm 2/s, abnormal digital rectal and amination in 5 cases, smoking in 7 cases, and alcohol consumption in 4 cases. The median PV [62.90(38.48, 71.96) vs. 37.21(29.22, 47.82)ml, P<0.01], the PSA value [5.55(2.99, 20.52) vs. 23.53(11.14, 65.98)ng/ml, P<0.01], and the PSAD value [0.16(0.07, 0.24) vs. 0.58(0.31, 1.57)ng/ml 2, P<0.01] were significantly different between benign condition group and prostate carcinoma group. Benign condition group included 5 chronic prostatitis, 2 acute prostatitis (1 with focal adenocarcinoma), 2 granulomatous inflammation, and 2 tuberculous granulomatous inflammation. In 7 benign cases, PSA was less than 10 ng/ml, combined with frequent urination, urgency of urination and incontinence were founded. In 8 benign cases, the area of lesion was more than 50% of the total prostate area in the axial position and the imaging of magnetic resonance were diffused, with regular shape and uniform signal. The imaging of symmetrical distribution was in 6 cases. Conclusions:The benign condition with PI-RADS 5 lesions included chronic prostatitis, acute prostatitis, granulomatous inflammation and tuberculous granulomatous inflammation, among which prostatitis was the most common cause. The PSA value were less than 10 ng/ml in most benign cases, with symptoms such as frequent urination, urgency of urination and incontinence. The imaging of magnetic resonance were diffused, symmetrically distributed, with regular shape and uniform signal.

Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.
Mice ; Animals ; Diabetes Mellitus, Experimental/metabolism* ; Axons/physiology* ; Diabetic Neuropathies ; Sensory Receptor Cells/metabolism* ; Neuralgia/metabolism*

Objective:To analyze the pulmonary high resolution CT (HRCT) images before and after hematopoietic stem cell transplantation (HSCT) in 6 children with Niemann-Pick disease(NPD) type B, and to investigate the effect of HSCT on lung lesions.Methods:Data of 6 children who were diagnosed with NPD type B and underwent HSCT treatment in Children′s Hospital Affiliated to Capital Institute of Pediatric from March 2019 to June 2021 were retrospectively enrolled, including 5 males and 1 female, with ages ranging from 1 year and 2 months to 5 years, and a median age of 2 years and 1month. The follow-up time of HRCT after HSCT was 7-20.5 months, the median time was 5 months, and the number of follow-up was 2-7 per patients, a total of 27 times. The pulmonary lesions (including interstitial lung disease, airway lesions and alveolar lesions) on aortic arch level, tracheal carina level and right diaphragmatic surface level were evaluated and scored respectively by two experienced pediatric radiologists, and the average score between them would be the final score. The Kruskal-Wallis H test was used to compare the scores of the three kinds of lung lesions before HSCT. The linear regression method was used to analyze the impact of HSCT duration on the degree of different lesions. To control possible confounding factors in the study, a generalized linear mixed model was used to evaluate the effects of HSCT duration, age, gender and whether co-infection on different types of lesions after HSCT. Results:Before HSCT treatment, all of the 6 children had different degree of airway, interstitial and alveolar lesions, with a median score of 3.0, 14.0 and 5.8 points, respectively (χ2=11.95, P=0.003). Interstitial disease was the most extensive and serious lesion among those three pulmonary involvements in pediatric NPD type B. After HSCT treatment, the scores of interstitial and airway lesions in all of the 6 children reduced, in varying degree, with the increase of time after HSCT. Except case 4, the alveolar lesion in 5 patients also showed a decreasing trend over time. The linear regression equation between the score of airway, interstitial, alveolar lesions and the HSCT duration was: airway lesion, Y=1.94-0.15X; interstitial lesion, Y=12.73-0.78X; and alveolar lesion, Y=3.31-0.27X. The results of the generalized linear mixed model showed that the main effect of HSCT duration significantly affected on the three kinds of lung lesions, and the scores of interstitial lesions, airway lesions and alveolar lesions were decreased by 0.688, 0.245, and 0.338 points for each 1 month increase of HSCT duration (all P<0.05). The alveolar lesion score decreased by 1.135 points for each 1 year increase in age at presentation ( P=0.012). The main effects of gender and co-infection were not statistically significant in all of the pulmonary lesions (both P>0.05). Conclusion:HSCT alleviates pulmonary lesions of children with NPD type B significantly and consistently, with interstitial lesions were the most prominent.