Objective:To investigate the expression of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues and analyze their expression levels in relation to clinical features and prognosis. Methods:From January 1, 2019, to December 31, 2019, 69 cases of nasopharyngeal carcinoma tissues and adjacent non-cancerous tissues were collected from patients treated at Yunnan Cancer Hospital. Immunohistochemistry was employed to detect the expression of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues. The Kaplan-Meier method was used to predict survival time, and the clinicopathological features were evaluated using the log-Rank test. Results:The positive expression rates of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues were 87.0% and 84.5%, respectively. Compared to adjacent normal tissues, the expression levels of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues were significantly increased （P<0.05）. Furthermore, the expression of NFAT5 and IGF1R was positively correlated with T stage, N stage, skull base invasion, and cranial nerve palsy （P<0.05）. The overexpression of NFAT5 and IGF1R significantly affected the survival rate of patients with nasopharyngeal carcinoma and was negatively correlated with prognosis （P<0.05）. Conclusion:In nasopharyngeal carcinoma tissues, overexpression of NFAT5 and IGF1R is observed, which is closely linked to clinical features and patient outcomes. These markers may serve as valuable indicators for predicting the prognosis of nasopharyngeal carcinoma.
Humans ; Nasopharyngeal Carcinoma/pathology* ; Nasopharyngeal Neoplasms/metabolism* ; Prognosis ; Female ; Receptor, IGF Type 1/metabolism* ; Male ; Transcription Factors/metabolism* ; Middle Aged ; Survival Rate ; Adult ; Neoplasm Staging

Objective:Retrospective analysis of the correlation between clinicopathologic features and related indexes and prognosis in patients with recurrent nasopharyngeal carcinoma. Methods:One hundred and eight nasopharyngeal cancer（NPC） patients with post-treatment recurrence in Yunnan Cancer Hospital from January 2013 to January 2018 were collected, and the survival time was estimated by Kaplan-Meier method, and clinicopathological characteristics were analyzed by log-rank test; risk factors and prognosis were analyzed by Cox proportional risk model for single-factor and multifactorial analysis. A P-value <0.05 was considered statistically significant. Results:The median survival of all patients was 54 months, with a 3-year survival rate of 80.2% and a 5-year survival rate of 39.8%. The 5-year overall survival rate was 50.2% for patients >46 years old and 27.9% for patients ≤46 years old（P<0.05）, a statistically significant difference. Univariate analysis showed that overall survival was associated with age, chemotherapy regimen, EBV early antigen IgA, plasma D-dimer, glycan antigen-125, γ-interferon, α-tumor necrosis factor, IL-10, and IL-4（P<0.05）. Multifactorial analysis revealed that age, chemotherapy regimen, EBV early antigen IgA, plasma D-dimer, glycan antigen-125, and interleukin 10 were independent influences on the prognosis of recurrent nasopharyngeal carcinoma（P<0.05）. Conclusion:Differences in chemotherapy regimens affect the prognosis of recurrent nasopharyngeal carcinoma. Elevated plasma D-dimer, glycan antigen 125, and interleukin 10 levels affect the overall survival of recurrent nasopharyngeal carcinoma, which may be a valid independent prognostic factor, and are expected to provide new biomarkers for nasopharyngeal carcinoma in the clinic.
Humans ; Prognosis ; Nasopharyngeal Neoplasms/mortality* ; Nasopharyngeal Carcinoma ; Retrospective Studies ; Neoplasm Recurrence, Local ; Male ; Middle Aged ; Female ; Survival Rate ; Adult ; Risk Factors ; Interleukin-10/blood* ; Aged ; Proportional Hazards Models

Objective:To explore the role of arginine metabolism in the inflammatory response to influenza A virus (FluA) infection.Methods:Eighteen-month-old mice were infected with FluA via nasal drip, with samples collected on the 6th day post-infection. The concentration of cytokines was determined by the Luminex multifactor assay, while the metabolites in bronchoalveolar lavage fluid (BALF) were analyzed using targeted metabolomic method. Correlation analysis was employed to examine the correlation between cytokines and metabolites. Macrophages were infected with FluA at a multiplicity of infection (MOI) of 1 and cultured with different concentrations of arginine for 24 h. The mRNA and protein expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α) and IL-10 were detected by real time fluorescence quantitative RT-PCR (qRT-PCR) and Cytometric Bead Array (CBA).Results:In comparison to the control group, the levels of surfactant protein D (SP-D), TNF-α, monocyte chemotactic protein-1 (MCP-1), IL-1α, IL-6, IL-10, recombinant S100 calcium binding protein (S100) A9, interferon inducible protein 10 (IP-10), macrophage inflammatory protein-1α (MIP-1α), matrix metalloprotein-9 (MMP-9), and Complement Factor D in BALF of FluA infection exhibited a significant elevation. The concentrations of arginine, aspartate, citrulline, glutamic acid, ornithine, proline, creatine, and sarcosine in arginine metabolism were up-regulated, which was correlated with most of elevated cytokine levels. The supplementation of arginine after FluA infection significantly decreased the levels of IL-1β, IL-6, and TNF-α, but increased the level of IL-10 in macrophages.Conclusions:Arginine reduces the inflammatory response induced by FluA infection in macrophages, suggesting that it may be a potential intervention target for severe pulmonary inflammation following FluA infection.

Diagnosis and treatment of hepatitis B virus (HBV) infection in children is a hotspot of concern in the field of HBV infection. This article reviews the current status and progress of antiviral treatment for children with chronic hepatitis B (CHB) in recent years, focusing on clinical issues such as the choice of antiviral treatment regimen for children with HBeAg-positive CHB (immune-clearance phase), the necessity of antiviral treatment for children with HBeAg-positive HBV infection (immune-tolerance phase), and the timing of antiviral treatment for infants with HBV infection, to explore the relevant factors that may affect the clinical cure of children with CHB. At the same time, based on the expert consensus on the prevention and treatment of children with CHB just published by Chinese experts, relevant diagnosis and treatment plans are proposed, with a view to providing reference and basis for clinical decision-making in children with CHB.

ObjectiveExploring the role of microRNA126 （miRNA126） in chronic kidney disease combined with atherosclerosis （CKD AS） by regulating the phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway and the mechanism of Shenshuai Xiezhuo decoction in the intervention of CKD AS rats with 5/6 nephrectomy combined with high-fat feeding. MethodA total of 60 SD rats were randomly divided into sham operation group， model group， losartan group， and low， medium， and high dose groups of Shenshuai Xiezhuo decoction. The CKD AS rat model was established by 5/6 nephrectomy combined with high-fat feeding for 10 weeks. The low， medium， and high dose groups （6.0， 12.0， 24.0 g·kg^-1·d^-1） of Shenshuai Xiezhuo decoction and the losartan group （20 mg·kg^-1·d^-1） were gavaged， and the corresponding intervention was carried out for eight weeks. Then， the rats were killed， and samples were collected for corresponding detection. Fully automated biochemical analyzers were used to detect kidney function and blood lipids in rats： blood creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） levels. Hematoxylin-eosin （HE） and Masson staining of aortic tissue and pathological observation under a light microscope were carried out， and autophagosomes and autophagy lysosomes were observed by transmission electron microscopy. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA levels of miRNA126， PI3K， Akt， and mTOR in rats， and Western blot was used to determine the protein expression levels of phosphorylated （p）-PI3K， PI3K， p-Akt， Akt， p -mTOR， mTOR， benzyl chloride 1 （Beclin-1）， and microtubule-associated protein light chain 3Ⅱ/Ⅰ （LC3Ⅱ/LC3Ⅰ）. ResultCompared with the sham operation group， the serum SCr， BUN， TC， TG， and LDL-C in the model group were significantly increased （P<0.01）. Compared with the model group， the SCr， BUN， TC， TG， and LDL-C were decreased in the losartan group and low， medium， and high dose groups of Shenshuai Xiezhuo decoction （P<0.05）. Compared with the sham operation group， thickening plaques， infiltration of mononuclear macrophages， a small number of foam cells， disordered arrangement of smooth muscle fibers in the tunica media， and increased collagen fibers were observed in the model group， and the lesions in the losartan group and Shenshuai Xiezhuo decoction groups were alleviated compared with those in the model group. Compared with the model group， the number of autophagosomes and autophagy lysosomes increased in the medium and high dose groups of Shenshuai Xiezhuo decoction. Compared with the sham operation group， the expression of miRNA126 in the aortic tissue of the model group was significantly decreased （P<0.01）， and the mRNA expressions of PI3K， Akt， and mTOR were significantly increased （P<0.01）. Compared with the model group， the expression of miRNA126 in the aortic tissue of rats in high， medium， and low dose groups of Shenshuai Xiezhuo decoction and losartan group was significantly increased （P<0.01）， while the mRNA expressions of PI3K， Akt， and mTOR were significantly decreased （P<0.01）. Compared with the sham operation group， the protein expressions of p-PI3K， PI3K， p-Akt， Akt， p-mTOR， and mTOR in the model group were significantly increased （P<0.01）， while the protein levels of Beclin-1， LC3Ⅰ， and LC3Ⅱ were significantly decreased （P<0.01）. Compared with the model group， the protein expressions of p-PI3K， PI3K， p-Akt， Akt， p-mTOR， and mTOR in the losartan group and low， medium， and high dose groups of Shenshuai Xiezhuo decoction were decreased （P<0.05）， while the protein levels of Beclin-1 and LC3Ⅱ/LC3Ⅰ were increased （P<0.05）. ConclusionThe expression of miRNA126 is decreased in the aortic tissue of CKD AS rats， and the PI3K/Akt/mTOR pathway is activated to inhibit autophagy flux. Shenshuai Xiezhuo decoction regulates the PI3K/Akt/mTOR signaling pathway through miRNA126， restores the autophagy of aortic endothelial cells， protects the damage of CKD vessels， reduces the formation of As plaques， and slows the development of cardiovascular complications.

Objective:To investigate the status of corneal epithelial remodeling and changes in corneal aberration after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and FS-LASIK combined with corneal collagen cross-linking (FS-LASIK Xtra), and to analyze the relationship between corneal epithelial thickness (CET) and corneal aberration.Methods:A cohort study was conducted.A total of 172 patients (172 eyes) who underwent FS-LASIK at Yinhai Eye Hospital of Chengdu University of Traditional Chinese Medicine were enrolled from June 2021 to February 2022.The 172 eyes were divided into FS-LASIK group (94 eyes) and FS-LASIK Xtra group (78 eyes) according to the surgical procedure, with a total follow-up of 6 months.The cornea was divided into a central 2-mm ring and a ring of 2-5 mm centered on the central cornea.CET at 9 regions in the central 0-5 mm area was measured by OCT before and at 1, 3 and 6 months after surgery, and the corneal higher-order aberration (HOA) was measured by the iTrace visual function analyzer.The main outcomes were the increase in CET (ΔCET), and corneal HOA at 6 months after surgery.The relationship between central corneal ΔCET and corneal aberration was analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Yinhai Eye Hospital of Chengdu University of Traditional Chinese Medicine (No.2021yh-009). Written informed consent was obtained from each subject.Results:At 1, 3 and 6 months after surgery, the central, superior, superior nasal, nasal, inferior nasal, inferior, inferior temporal, temporal and superior temporal ΔCET were significantly smaller in FS-LASIK Xtra group than in FS-LASIK group (all at P<0.05). In FS-LASIK Xtra group, 6-month postoperative central, superior, superior nasal, inferior and inferior temporal ΔCET were significantly larger than those at 1 month after surgery, and 3- and 6-month postoperative temporal ΔCET were significantly larger than that at 1 month after surgery, and 6-month postoperative superior temporal ΔCET was significantly larger than those at 1 and 3 months after surgery (all at P<0.05). In FS-LASIK group, 3- and 6-month postoperative central, superior, inferior and inferior temporal ΔCET were significantly larger than those at 1 month after surgery, and 6-month postoperative superior nasal ΔCET was significantly larger than that at 3 months after surgery, and 6-month postoperative nasal, inferior nasal, temporal, superior temporal ΔCET were significantly larger than those at 1 and 3 months after surgery (all at P<0.05). There was no significant difference in vertical trefoil, vertical and horizontal coma changes at different time points after surgery between both groups (vertical trefoil: χ2group=4.27, P=0.118; χ2time=0.01, P>0.05.vertical coma: χ2group=5.74, P=0.057; χ2time=0.08, P=0.957.horizontal coma: χ2group=3.97, P=0.137; χ2time=0.51, P=0.773). The tilted trefoil changes at 1, 3 and 6 months after surgery of FS-LASIK Xtra group were significantly larger than those of FS-LASIK group (all at P<0.05). The 6-month spherical aberration change in FS-LASIK Xtra group was significantly higher than that at 1 month after surgery, and the 6-month spherical aberration change in FS-LASIK group was significantly higher than that at 1 and 3 months after surgery (all at P<0.05). The 6-month total HOA change in FS-LASIK group was significantly lower than that at 1 and 3 months after surgery (all at P<0.05). In FS-LASIK group, central corneal ΔCET was weakly positively correlated with spherical aberration at 1 and 6 months after surgery ( rs=0.257, P=0.008; rs=0.244, P=0.012), and was weakly positively correlated with total HOA ( rs=0.253, P=0.009; rs=0.279, P=0.004). Conclusions:The postoperative ΔCET after FS-LASIK Xtra is smaller than that after FS-LASIK, but the homogeneity of ΔCET in each region is similar between the two groups.The changes in corneal HOA after surgery are similar in both groups, and there is a certain association between the overall epithelial distribution and corneal aberration.

Objective:To observe the effect of nutrition intervention and exercise rehabilitation treatment on the sarcopenia in elderly patients with type 2 diabetes.Methods:It was a cross-sectional study. From March 2019 to September 2020, 101 elderly patients with type 2 diabetes complicated with sarcopenia treated in the Department of Endocrinology of Tianjin Third Central Hospital were enrolled in this study. The patients were divided into four groups with propensity score matching method: sarcopenia education group without nutrition and resistance training group (group A, n=22), simple nutrition intervention group (group B, n=28), nutritional intervention combined with resistance training group (group C, n=27) and nutritional intervention combined with aerobic and resistance training group (group D, n=24). All the patients were intervened for 24 weeks, two patients in groups C and D dropped due to their own reasons. The 25-dihydroxy vitamin D3 (25(OH)D 3), grip strength, muscle mass of the limbs and short physical performance battery (SPPB) scores were measured before and 24 weeks after the intervention in all the participants. Results:After the intervention, the 25(OH)D 3 levels in the B, C, D groups was (33.45±4.05), (33.68±4.69), (34.28±5.58) μg/L, respectively, all were higher than those before the treatment (all P<0.01), and there was no significant differences among the three groups ( P>0.05). The muscle mass in the B, C, D groups after intervention was 5.650 (5.102, 6.658), 6.601 (6.007, 7.156) and 6.520 (6.017, 7.302) kg/m 2, respectively, all were significantly higher than those before the treatment (all P<0.01); the muscle mass in group C and D increased more significantly than that in group B ( P<0.01), but there was no significant differences between group C and D ( P>0.05). After the intervention, the muscle strength in the C and D groups was 20.60 (19.20, 24.55) kg and 21.15 (19.43, 26.63) kg, and the SPPB scores was 8.00 (7.00, 9.00) points and 8.00 (8.00, 9.00) points, respectively, all were higher than those before the intervention (all P<0.01), but there was no significant differences between the two groups(both P>0.05). The SPPB function score in group D was better than that in group C, the difference was statistically significant ( P<0.05). Conclusions:Nutritional intervention can improve the muscle mass in elderly type 2 diabetes patients with sarcopenia. Combined with rehabilitation training, the muscle strength and muscle function of these patients could also be improved, and the improvement of muscle mass is better than that in patients receiving nutritional intervention only. In terms of increasing muscle strength, the two kinds of rehabilitation training are equivalent. If combined with aerobic exercise, it can also improve the muscle function of these patients.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

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.

Objective:To study the correlation between patients with type 2 diabetes mellitus combined with nonalcoholic steatohepatitis in order to provide theoretical support for the treatment of NAFLD through aerobic exercise performance.Methods:253 cases with T2DM combined with NAFLD were selected. 93 cases consented to undergo a liver biopsy. Among them, 74 cases with liver biopsy successfully passed the symptom-limited cardiopulmonary exercise test (CPET) and respiratory quotient (RQ)≥1.05. Patients were divided into two groups according to the NAFLD activity score (NAS) of the pathological biopsy: the non-NASH group (NAS < 4) and the NASH group (NAS≥4). The differences in general clinical and biochemical indicators and exercise parameters were compared between the two groups. The relevant factors that affect aerobic exercise performance in NAFLD patients were explored by correlation and regression analysis.Results:The peak oxygen uptake [VO2 @ peak, (17.82 ± 5.61) ml·kg -1·min -1 and (23.14 ± 5.86) ml·kg -1·min -1] and anaerobic threshold [VO2 @ AT, (11.47 ± 3.12) ml·kg -1·min -1 and (13.81 ± 3.53) ml·kg -1·min -1] were lower in the NASH group than those in the non-NASH group in T2DM patients, with P < 0.01, indicating a significant decrease in aerobic exercise performance in NASH patients compared to non-NASH patients. Correlation analysis showed that patients with T2DM combined with NAFLD VO2@peak was positively correlated with RQ, carbohydrate oxidation rate (%CHO), daily carbohydrate energy supply (CHO Kcal/d), high-density lipoprotein cholesterol (HDL-C), and maximal voluntary ventilation (MVV) ( r 0.360, 0.334, 0.341, 0.255, 0.294, P < 0.05 or P < 0.01, respectively) and negatively correlated with NAS score, fat attenuation, liver stiffness, fat oxidation rate (%FAT), daily fat energy supply (FAT Kcal/d), aspartate aminotransferase (AST), alanine aminotransferase (ALT), body mass, and body mass index (BMI) ( r -0.558, -0.411, -0.437, -0.340, -0.270, -0.288, -0.331, -0.295, -0.469, P < 0.05 or P < 0.01, respectively). VO2@AT were positively correlated with RQ, %CHO, total cholesterol (TC), and HDL-C ( r 0.351, 0.247, 0.303, 0.380, P < 0.05 or P < 0.01, respectively), while it was negatively correlated with NAS score, fat attenuation, liver stiffness, %FAT, FAT (Kcal/d), ferritin (Fer), ALT, AST, body weight, and BMI ( r -0.330, -0.384, -0.428, -0.270, -0.318, 0.320, -0.404, -0.416, -0.389, -0.520, P < 0.05 or P < 0.01, respectively). Stepwise multiple regression analyses revealed that BMI, RQ, and NAS scores were independent correlated factors of aerobic exercise performance. Conclusion:Hepatic inflammation and fibrosis affect the aerobic exercise performance of patients with T2DM combined with NAFLD.