Objective:To investigate the diagnostic performance of different thyroid imaging reporting and data systems (TI-RADS) in the diagnosis of medullary thyroid carcinoma (MTC) .Methods:A total of 160 thyroid nodules diagnosed as MTC by postoperative pathology from Aug. 2011 to Aug. 2022 at the First Affiliated Hospital of Zhengzhou University were included. Additionally, 160 papillary thyroid carcinomas (PTC) and 160 benign nodules were randomly selected as controls during the same period. Differences in gender, age, nodule diameter and various ultrasound features were observed. The nodules were classified according to American College of Radiology (ACR) TI-RADS, artificial intelligence (AI) TI-RADS and Chinese (C TI-RADS). Then, receiver operating characteristic curve (ROC) were plotted to calculate the diagnostic value. The Kendall concordance coefficient was used to evaluate the interobserver consistency of each TI-RADS system.Results:There was no statistically significant difference in gender among the three groups ( χ2=1.17, P=0.558). However, significant differences were observed in age and nodule diameter ( F=12.08,40.12, P<0.001 for both). The area under ROC (AUC) for diagnosing MTC and benign nodules using ACR, AI, and C-TIRADS were 0.762, 0.773, and 0.761, respectively, with no statistically significant differences ( Z=1.33, 0.01, 0.87, P=0.183, 0.994, 0.386). However, the sensitivity of C TI-RADS (87.5%) was lower than that of ACR and AI TI-RADS (both 95.0%) ( P=0.018). After combining the biopsy threshold, the false negative rate of C-TIRADS was lower than that of ACR (30.6% vs. 41.3%) ( P=0.048) and AI TIRADS (30.6% vs. 43.1%) ( P=0.020). The inter-observer diagnostic consistency of C-TIRADS was superior to ACR (0.884 vs. 0.819, P<0.001) and AI TIRADS (0.884 vs. 0.839) ( P<0.001) . Conclusions:AI and ACR TI-RADS have higher sensitivity in diagnosing MTC, while C TI-RADS has a lower puncture missed diagnosis rate. AI has similar diagnostic performance to ACR TI-RADS and can replace ACR TI-RADS.

Purpose::To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis.Methods::A total of 282 healthy young male volunteers aged 18 -20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conformed to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q 1, Q 3) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy. Results::Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4% (66 cases). These patients showed higher percentages of lean body mass ( p = 0.001), total body water (TBW, p=0.006), extracellular water ( p=0.020) and intracellular water ( p=0.010) as well as a larger ratio of basal metabolic rate/total weight ( p=0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat ( p=0.001) and body fat mass index ( p=0.002) were lower. Logistic regression analysis showed that TBW percentage > 65.35% ( p=0.050, odds ratio =3.114) and 3rd space water > 0.95% ( p=0.045, odds ratio =2.342) were independent risk factors for lower extremity muscle injuries. Conclusion::TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

Renal fibrosis is a devastating consequence of progressive chronic kidney disease,representing a major public health challenge worldwide.The underlying mechanisms in the pathogenesis of renal fibrosis remain unclear,and effective treatments are still lacking.Renal tubular epithelial cells(RTECs)maintain kidney function,and their dysfunction has emerged as a critical contributor to renal fibrosis.Cellular quality control comprises several components,including telomere homeostasis,ubiquitin-proteasome system(UPS),autophagy,mitochondrial homeostasis(mitophagy and mitochondrial metabolism),endoplasmic reticulum(ER,unfolded protein response),and lysosomes.Failures in the cellular quality control of RTECs,including DNA,protein,and organelle damage,exert profibrotic functions by leading to senescence,defective autophagy,ER stress,mitochondrial and lysosomal dysfunction,apoptosis,fibro-blast activation,and immune cell recruitment.In this review,we summarize recent advances in un-derstanding the role of quality control components and intercellular crosstalk networks in RTECs,within the context of renal fibrosis.

Based upon the experiences of planning and implementation of "Dynamic changes of Torque Teno virus load in Chinese renal transplant recipients with immunosuppressive therapy: A multi-center prospective observational double-blind cohort study", this article explored the current status and major difficulties of investigator-initiated multi-center prospective clinical trials of kidney transplantation in China. Various issues of organization design and implementation process management were discussed for enhancing the quality of implementing the relevant trials.

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.

AIM: To explore the clinical efficacy of different anti-vascular endothelial growth factor(VEGF)drugs in the treatment of diabetic macular edema(DME), and analyze their relationship with optical coherence tomography(OCT)classification.METHODS: A total of 45 DME patients treated with ranibizumab(admitted to our hospital from February 2020 to February 2022)were selected as the ranibizumab group, and 45 DME patients treated with conbercept during the same period were selected as the conbercept group. The ranibizumab group was treated with retinal photocoagulation combined with ranibizumab, and the conbercept group was treated with retinal photocoagulation combined with conbercept. The improvement of symptoms(improvement time of macular edema, time of retinal thickness returning to normal, disappearance time of neovascularization and absorption time of fundus hemorrhage), levels of serum interleukin-6(IL-6)and VEGF, central macular thickness(CMT), best corrected visual acuity(BCVA), and complications were compared between the two groups, and the relationship between their clinical efficacy and different OCT types were analyzed.RESULTS: There was no significant difference in the improvement time of macular edema, time of retinal thickness returning to normal, disappearance time of neovascularization and absorption time of fundus hemorrhage between the two groups(P>0.05); After treatment, the values of IL-6, VEGF and BCVA in the two groups were significantly lower than those before treatment(P<0.01), but there was no significant difference between the two groups(P>0.05); compared with before treatment, CMT was significantly decreased in both groups after treatment(P<0.05), and compared with ranibizumab group, the CMT was significantly decreased in the conbercept group(P<0.01); there was no significant difference in the incidence of complications between two groups(P>0.05); there were significant differences in the total effective rate among patients with serous retinal detachment(SRD), cystoid macular edema(CME)and diffuse retinal thickening(DRT; P<0.05), among which DRT had the highest total effective rate and SRD had the lowest total effective rate.CONCLUSION: Both conbercept and ranibizumab in the treatment of DME can effectively improve the clinical symptoms of patients and reduce the inflammatory response, but conbercept can better reduce the level of CMT, and has better treatment effect on DRT-type DME patients.

Objective: To evaluate the clinical outcomes of computer aided design and computer aided manufacturing (CAD/CAM) ceramic endocrowns in endodontically treated posterior teeth after five years by a retrospective study. Methods: Patients who received CAD/CAM ceramic endocrowns after endodontically treatment in Department of Endodontics, School of Stomatology, The Fourth Military Medical University between January 2016 and June 2017 were invited for this clinical study. Clinical performance was evaluated in the aspect of color match, anatomic form,marginal adaptation, restoration integrity and secondary caries. Survival rate of the restorations was calculated by the use of Kaplan-Meier method. Log-rank test was applied as well for the sake of analyzing the effect of tooth position, sex and materials to the survival rate of the restorations. Results: Seventy-four patients, 25 men and 49 women with age of (38.8±10.2) years, participated in this study for a total of 101 CAD/CAM ceramic endocrowns after observation period of (62.8±12.0) months. There were 8 failed cases among 101 restorations, 5 were loss of retention, 2 were ceramic fracture and 1 was secondary caries respectively. In particular, 93% (89/96) restorations got score A on anatomic form and 95% (91/96) restorations got score A on marginal adaptation, while 38% (36/96) restorations showed the good color match compared with the abutment teeth. The estimated cumulative survival rate of CAD/CAM ceramic endocrowns in endodontically treated posterior teeth after 5 years was 93.0% (95%CI: 87.9%-98.1%). The single-factor Log-rank analysis demonstrated that there was no statistically significant difference in the survival rate of CAD/CAM ceramic endocrowns among men and women, premolars and molars, position in the dental arch, or different materials (χ²<0.01, P=0.957; χ²=0.64, P=0.422; χ²=0.69, P=0.407; χ²=0.88, P=0.349). Conclusions: Based on this clinical study, the clinical performance of CAD/CAM ceramic endocrowns in endodontically treated posterior teeth after five years is reliable, which could be a general option to restore nonvital teeth.
Humans ; Male ; Female ; Adult ; Middle Aged ; Crowns ; Dental Porcelain/therapeutic use* ; Retrospective Studies ; Dental Prosthesis Design ; Dental Stress Analysis ; Materials Testing ; Computer-Aided Design ; Ceramics

ObjectiveTo explore the molecular mechanism of "transmission between the lung and brain" of influenza based on Janus kinase 1/signal transducer and activator of transcription 1（JAK1/STAT1） signaling pathway and further investigate the intervention effect of Maxing Shigantang （MXSGT）. MethodA total of 100 SPF BALB/c mice were randomly divided into a normal group，a model group，an oseltamivir group （21.63 mg·kg^-1·d^-1），an antiviral granules group（3.9 g·kg^-1·d^-1）， and an MXSGT group（6.05 g·kg^-1·d^-1）， with 20 mice in each group. The pneumonia model was induced in mice except for those in the normal group by intranasal infection of influenza A virus（IAV）. Twenty-four hours after modeling，mice were treated with corresponding drugs， while those in the normal group and the model group received the same amount of normal saline by gavage， once a day for 3 and 7 days. The pathological changes in the lung and brain were observed by hematoxylin-eosin（HE）staining. The mRNA expression of IAV nucleoprotein（NP），JAK1， and STAT1 in the lung and brain was detected by real-time quantitative polymerase chain reaction（Real-time PCR）， and the protein expression of JAK1 and STAT1 in the lung and brain was detected by Western blot. Immunohistochemical method was used to detect the expression of phosphorylated（p）-STAT1 in the lung and brain tissues， and enzyme-linked immunosorbent assay（ELISA） was used to detect the serum levels of interleukin-1β（IL-1β） and interleukin-10（IL-10）. ResultCompared with the normal group， the model group showed obvious pathological changes in the lung tissues and cerebral cortex， increased relative mRNA expression of IAV NP in the lung （P<0.01）， elevated mRNA and protein expression of JAK1 and STAT1 in the lung and brain tissues （P<0.05，P<0.01），up-regulated expression level of p-STAT1 in lung tissues and cerebral cortex （P<0.05，P<0.01）， and increased serum level of IL-1β （P<0.05）. Compared with the model group， the MXSGT group showed alleviated pathological damage to lung tissues and cerebral cortex， decreased relative mRNA expression of IAV NP in lung tissues（P<0.01），reduced mRNA and protein expression levels of JAK1 and STAT1 in lung tissues and brain tissues（P<0.05，P<0.01）， and increased serum level of IL-10（P<0.01）. ConclusionThe abnormal activation of the JAK1-STAT1 signaling pathway may be one of the molecular mechanisms of "transmission between the lung and brain" of influenza. As an effective compound prescription against the influenza virus，MXSGT can alleviate the pathological damage of brain tissues in mice infected with IAV by regulating the level of cytokines mediated by this pathway.

Objective:To explore the potential mechanism of PD-1 inhibitor P on RIMI from the perspective of immune microenvironment.Methods:To establish a mouse model of radiation-induced myocardial injury (RIMI), twenty C57BL/6 mice were randomly divided into 4 groups, 5 in each group. Group A was the healthy control group; Group B was the PD-1 inhibitor group; Group C was the simple irradiation group, with a heart irradiation of 15 Gy; Group D was the irradiation+ PD-1 inhibitor group. One month after irradiation, the mice were anesthetized and sacrificed. The morphological changes of myocardial tissues were observed by HE staining. The myocardial fibrosis was assessed by Masson staining. CD 3+ , CD 3+ CD 4+ , CD 3+ CD 8 lymphocyte subsets and cytokines (IL-4, IL-6, IL-17A, TNF-α, TGF-β 1 and INF-γ) levels were determined by flow cytometry. The apoptosis rate of myocardial cells was detected by TUNE. Results:One month after irradiation, there was no obvious myocardial fibrosis in group B, and collagen fibers were distributed in the interstitium of myocardial cells in groups C and D. Semi-quantitative analysis results showed that the myocardial collagen volume fraction (CVF) of groups A, B, C and D were (1.97±0.36)%, (2.83±1.03)%, (5.39±0.77)% and (7.72±1.43)%, respectively. The CVF between group A and group B was similar ( P=0.314), and the differences in CVF between the other groups were statistically significant (all P<0.05). Compared with group A, the absolute value and percentage of CD 3+ T lymphocytes were significantly increased in groups B, C and D (all P<0.01). The values in group D were significantly higher than those in group B and group C (all P<0.01); The absolute value and percentage of CD 3+ CD4 T lymphocytes were similar among four groups (all P>0.05); The absolute value and percentage of CD 3+ CD 8 T lymphocytes in group D were significantly higher than those in groups A, B and C (all P<0.001). The expression levels of IL-6, IL-17A, and TGF-β 1 in group D were significantly higher compared with those in groups A, B and C (all P<0.001). The apoptotic index was gradually increased in four groups, and the differences in apoptotic index among four groups were statistically significant (all P<0.001). Conclusion:PD-1 inhibitors can aggravate RIMI by promoting myocardial immune inflammatory response.