Objective:To compare the effects of different test meals on postprandial triglycerides and to optimize the standard meal composition and the blood sampling protocol for the oral fat tolerance test.Methods:This study is a prospective, open-label, randomized, cross-over trial. In March 2023, 36 volunteers were recruited in Hebei General Hospital. They underwent a health examination and oral glucose tolerance test. Twenty-six healthy volunteers(11 males and 15 females) were included in this study, with an average age of(39.08±4.56) years. Each volunteer received 75 g protein meal, 75 g fat meal, 700 kcal fixed-calorie high-fat mixed meal, and a high-fat mixed meal with energy adjusted based on 10 kcal/kg body weight. A one-week washout period of regular diet was applied before each trial. Blood was collected at fasting status and 1, 2, 3, 4, 5, and 6 hours after a meal to detect serum triglycerides, total cholesterol, low density lipoprotein-cholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), glucose, and insulin. The variations of postprandial metabolic indicators over time following the consumption of different test meals were analyzed. The disparities in postprandial metabolic responses between the two types of mixed meals were compared.Results:The protein meal, fat meal, fixed-calorie high-fat mixed meal, and adjusted-calorie high-fat mixed meal resulted in postprandial triglyceride increases of 22.45%, 115.40%, 77.14%, and 63.63%, and insulin increase of 560.43%, 85.69%, 554.18%, and 598.97%, respectively, and with reductions in total cholesterol, LDL-C, and HDL-C ranging from 5.64%-21.81%, respectively. The blood glucose changed slightly. Changes in metabolic indicators mainly occured within 4 hours. The comparison of the characteristics of postprandial triglycerides between the two high-fat mixed meals showed no statistically significant differences( P>0.05). Conclusion:A standardize protocol with a 700 kcal fixed-calorie high-fat mixed meal as test meal, and blood lipid levels measured at fasting and at 1, 2, 3, and 4 hours after consumption, can serve as an optimized approach for oral fat tolerance test.

Objective To investigate the expression,synergistic relationship and clinical significance of alcohol de-hydrogenase(ADH1A)and vascular endothelial growth factor-A(VEGFA)in hepatocellular carcinoma(HCC).Methods The expression and correlation of ADH1A and VEGFA in HCC and adjacent normal tissues were ana-lyzed by GEPIA.TCGA and GSEA were used to analyze the pathway of ADH1A in HCC.The clinical and patho-logical data of 84 patients with HCC were collected,and 54 patients with paracancer normal tissue samples were se-lected as controls to analyze the correlation between ADH1A and VEGFA and clinicopathological parameters of HCC.Immunohistochemistry was used to detect the protein expression of ADH1A and VEGFA in cases and con-trols,and the correlation between the expression of ADH1A and VEGFA and the clinical progression and prognosis of patients with HCC was analyzed based on clinical pathological parameters and Kaplan-Meier.Results Bioinfor-matics analysis found that ADH1A was low-expressed in HCC and VEGFA was highly expressed in HCC,and there was a negative correlation between the two(P<0.001);immunohistochemical detection results showed that the expression of ADH1A in HCC tissue was lower than that in normal tissue adjacent to cancer(P<0.01)while the expression rate of VEGFA in HCC tissue was significantly higher than that of normal tissue adjacent to cancer(P<0.01);The recurrence rate of vascular thrombus and HCC patients in HCC group with high expression of ADH1A was lower(P<0.05).The proportion of tumor diameter>5 cm,high TNM stage,microsatellite and G2-G3 dif-ferentiation in HCC tissues in VEGFA high expression group was higher(P<0.05).Kaplan-Meier survival analy-sis showed that patients with high ADH1A expression and low VEGFA expression had a higher five-year survival rate.Conclusion Low expression of ADH1A and high expression of VEGFA in tumor tissues of patients with HCC indicate tumor progression and can be used as one of the prognostic evaluation indicators for patients with HCC.

Objective:To discuss the effect of sialic acid-binding immunoglobulin-like lectin-15(Siglec15)derived from M2 tumor-associated macrophages(M2-TAMs)on promoting the malignant biological behavior of the esophageal squamous cell carcinoma(ESCC)through bioinformatics analysis,and to validate the findings through cell experiment.Methods:The Tumor Immune Estimation Resource(TIMER)online Database was used to analyze the expression differences and immune infiltration of Siglec15 in pan-cancer and adjacent normal tissues.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Siglec15 mRNA in M2-TAMs and ESCC EC109 and KYSE150 cells.Based on the non-contact co-culture of M2-TAMs and ESCC cells,the following groups were set up,such as EC109/KYSE150 group,EC109/KYSE150+si-NC group(transfected with si-NC sequence),and EC109/KYSE150+si-Siglec15 group(transfected with si-Siglec15#1 and si-Siglec15#2 sequences).CCK-8 method was used to detect the proliferation activities of the cells in various groups;wound healing assay was used to detect the wound healing rates of the cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion cells in various groups;flow cytometry was used to detect the apoptotic rates of the cells in various groups.Results:The bioinformatics analysis results showed that compared with adjacent normal tissue,the expression levels of Siglec15 mRNA in pan-cancer tissues such as esophageal cancer,colon cancer,and head and neck squamous cell carcinoma tissues were increased(P＜0.05 or P＜0.01),and the expression level of Siglec15 mRNA in esophageal cancer tissue was significantly positively correlated with the infiltration of the macrophages(P＜0.05).Compared with the EC109 cells and KYSE150 cells,the expression level of Siglec15 mRNA in M2-TAMs was significantly increased(P＜0.01).There was no significant difference in the proliferation rate of the cells among EC109/KYSE150 group,EC109/KYSE150+si-NC group,and EC109/KYSE150+si-Siglec15 group(P＞0.05).Compared with EC109/KYSE150 group,after treated for 24 and 48 h,the wound healing rate of the cells in EC109/KYSE150+si-NC group was increased(P＜0.01),the numbers of migration and invasion cells were increased(P＜0.05),and the apoptotic rate was decreased(P＜0.01).Compared with EC109/KYSE150+si-NC group,the wound healing rates of the cells in EC109/KYSE150+si-Siglec15#1 group and EC109/KYSE150+si-Siglec15#2 group were decreased(P＜0.05),the numbers of migration and invasion cells were decreased(P＜0.05),and the apoptotic rates of the cells had no significant difference(P＞0.05).Conclusion:Siglec15 derived from M2-TAMs may be a key factor in promoting the migration and invasion of the ESCC cells.

Objective:To explore the association between postoperative radiotherapy for bladder cancer and the risk of second primary rectal cancer.Methods:Eligible 75 120 patients with bladder cancer from the Surveillance, Epidemiology, and End Result database (SEER) of the National Cancer Institute (NCI) (1975-2017) were enrolled in this study. The second primary cancers referred to rectal cancers patients suffered after more than five years post-treatment for bladder cancer, and the cumulative incidence was estimated using Fine-Gray competing risk regression. The relative risk (RR) of rectal cancer in patients treated with or without radiotherapy (the RT group or the NRT group) was evaluated using Poisson regression.Results:Among the 75 120 patients, 70 045 (92.4%) were Caucasian, with a median age of 65.8 years (54-74 years). A total of 2 236 (3%) received postoperative radiotherapy, while 72 884 (97%) received surgery alone. The 30-year follow-up revealed a cumulative incidence of rectal cancer of 0.93% in the RT group and 0.43% in the NRT group ( P = 0.004). The competing risk regression analysis identified a significant association between radiotherapy and rectal cancer ( HR: 1.86; 95% CI 1.26-2.74, P < 0.009). Furthermore, the RR of radiotherapy-associated rectal cancer significantly increased as the diagnosis occurred earlier (1975-1985 vs. 1985-1994: RR 2.59; 95% CI 1.20-4.86, P < 0.001), and a lower age at the time of radiotherapy was associated with a higher probability of second primary tumors (≤50-year old vs. > 50 year old : RR 7.89, 95% CI 2.97-21.30, P < 0.001). As calculated using the Poisson distribution, the RR of second rectal tumors was higher in the RT group ( RR: 2.20, 95% CI 1.45-3.18, P < 0.001), even after adjusting the date of diagnosis ( RR: 1.77, 95% CI 1.17-2.57, P = 0.009). Conclusions:An increased risk of rectal cancer following bladder cancer radiotherapy necessitates aggressive follow-ups for the purpose of early detecting second primary rectal cancer associated with bladder cancer radiotherapy.

‍Traditionally， the progression from compensated liver cirrhosis to decompensated liver cirrhosis has been considered an irreversible point in the natural history of the disease； however， with the suppression of underlying etiology， cure， and disease regression， this view is challenged by an increasing number of new evidence， and the idea of “recompensation of liver cirrhosis” is gradually being accepted. In recent years， scholars in China and globally have been exploring the specific definition of recompensation of liver cirrhosis and the clinical features of patients. By summarizing the recent studies on recompensation of liver cirrhosis in China and globally， integrating existing views， and analyzing related research evidence， this article points out the main challenges in the field of recompensation at this stage， including the lack of in－depth clinical and basic research， the need to define recompensation in the context of NAFLD， and related ethical issues， in order to provide new directions for future research in this field.

‍Nonalcoholic fatty liver disease （NAFLD） is a group of highly heterogeneous diseases closely associated with metabolic dysfunction. Sarcopenia is a syndrome caused by a continuous decline in muscle mass， strength， and function， and it is often accompanied by NAFLD. Insulin resistance is the main pathological mechanism for sarcopenia and NAFLD， and in addition， factors such as changes in proteins and branched‍-‍chain amino acid， hyperammonemia， intestinal flora， and endocrine dysfunction can also lead to sarcopenia and NAFLD. With the deepening of clinical research， many published prospective studies have confirmed the existence of a bidirectional and complex pathophysiological relationship between sarcopenia and NAFLD. This article reviews the bidirectional relationship between sarcopenia and NAFLD， discusses the common pathogenesis of sarcopenia and NAFLD， summarizes the challenges faced in this field， and proposes new directions for the research on the bidirectional relationship between NAFLD and sarcopenia.

The axon initial segment (AIS) is a highly specialized axonal compartment where the action potential is initiated. The heterogeneity of AISs has been suggested to occur between interneurons and pyramidal neurons (PyNs), which likely contributes to their unique spiking properties. However, whether the various characteristics of AISs can be linked to specific PyN subtypes remains unknown. Here, we report that in the prelimbic cortex (PL) of the mouse, two types of PyNs with axon projections either to the contralateral PL or to the ipsilateral basal lateral amygdala, possess distinct AIS properties reflected by morphology, ion channel expression, action potential initiation, and axo-axonic synaptic inputs from chandelier cells. Furthermore, projection-specific AIS diversity is more prominent in the superficial layer than in the deep layer. Thus, our study reveals the cortical layer- and axon projection-specific heterogeneity of PyN AISs, which may endow the spiking of various PyN types with exquisite modulation.
Mice ; Animals ; Axon Initial Segment ; Synapses/physiology* ; Pyramidal Cells/physiology* ; Cerebral Cortex ; Axons/physiology*

Objective:To explore the expression of serum inflammatory factors in patients with thyroid tumor and their correlation with thyroid hormones.Methods:A total of 92 patients with thyroid tumors (48 cases of thyroid cancer and 44 cases of thyroid adenoma) admitted to Department of Endocrinology in Linyi Central Hospital in Shandong Province from Jan. 2020 to Oct. 2021 were enrolled. 50 healthy volunteers who received physical examination in the hospital during the same period were enrolled in the control group. The serum inflammatory factors [tumor necrosis factor-α (TNF-α) , interleukin-6 (IL-6) , interleukin-17 (IL-17) ] and thyroid hormone expression levels [thyroid stimulating hormone (TSH) , free thyroxin T4 (FT4) , free triiodothyronine (FT3) ] of the three groups were detected. Analysis of variance was used for multi-group comparison, independent sample t test was performed for comparison between groups, Spearman correlation analysis and Logistic regression analysis were made for the risk factors of thyroid cancer. The expression of serum inflammation and thyroid hormones in patients with different stages of thyroid cancer was observed. Results:Serum TNF-α, IL-17, IL-6 from high to low were in the thyroid cancer group (74.61±7.94 ng/L, 68.65±7.05 ng/L, 20.52±2.84 ng/L) , thyroid adenoma group (26.97±3.42 ng/L, 46.31±5.31 ng/L, 13.61±1.58 ng/L) , control group (18.82±2.63 ng/L, 34.52±4.02 ng/L, 8.97±1.06 ng/L) ( F=1596.271, 468.602, 423.351, all P<0.001) ; Serum TSH levels from high to low were in the thyroid cancer group (8.64±1.34 mU/L) , the thyroid adenoma group (5.21±1.02 mU/L) , the control group (3.94±0.85 mU/L) ( F=242.182, P=0.000) . There was no significant difference in serum FT4 or FT3 levels among the three groups ( P=0.753, 0.634) . Correlation analysis indicated that serum TNF-α, IL-17, and IL-6 were positively correlated with the expression level of serum TSH ( r=0.936, 0.726, 759, all P<0.05) . The expression level of TNF- α, IL-17, IL-6 and TSH was significantly higher in patients of stage III and IV than that in patients of stage I and II ( t=2.541, 4.394, 6.390, 4.962, P=0.015, P<0.001, P<0.001, P<0.001) . Multivariate Logistic regression analysis suggested serum TNF-α, IL-17, IL-6 and TSH were all risk factors for thyroid cancer. Conclusions:Serum inflammatory factors and some thyroid hormones (TSH) are generally highly expressed in patients with thyroid tumors, the expression levels of serum inflammatory factors are correlated with the expression of TSH. There are statistically significant differences in the expression levels of serum inflammatory factors and TSH between patients with thyroid cancer of different stages, serum inflammatory factors and TSH are also involved in the occurrence and development of thyroid cancer, and are risk factors for thyroid cancer.

Objective:To analyze the clinical features and genetic basis for a child featuring elevated creatine kinase (CK).Methods:Next-generation sequencing (muscular dystrophy-related gene panel) was carried out for the proband. Candidate variants were verified by Sanger sequencing of the child and his parents.Results:The child was found to harbor compound heterozygous variants of the FKTN gene, including a missense c. 536G>C (p.R179T) variant from his father and a non-frameshift c. 1299_1301delGTG (p.W434del) variant from his mother. Both variants were predicted to be pathogenic. Conclusion:The compound heterozygous variants of the FKTN gene probably underlay the disease in this child. Above finding has expanded the mutation spectrum of congenital muscular dystrophy.

Objective:To investigate the efficacy and safety of individualized rituximab rescue therapy for active lupus nephritis with acute kidney injury (AKI).Methods:The clinical data of lupus nephritis patients with AKI treated with rituximab at the Kidney Disease Center of the First Affiliated Hospital of Zhejiang University School of Medicine from April 2017 to June 2020 were collected, and the renal remission rate and adverse events after rituximab treatment were analyzed retrospectively. The Kaplan-Meier method was used to calculate the cumulative incidence of patients' remission.Results:There were 13 patients enrolled, including 8 females, and aged (35.23±15.92) years old. The urinary protein/creatinine ratio was (5.22±1.57) g/g before rituximab treatment. Four patients were on dialysis at admission, and 9 patients without dialysis had serum creatinine of (223.22±85.73) μmol/L. Eight patients were confirmed as proliferative lupus nephritis by renal biopsies, including 7 cases with crescent formation and 1 case with thrombotic microangiopathy (TMA), and the other 5 cases without renal biopsies were clinically diagnosed as TMA. The dose of rituximab was (815±516) mg (200-2 100 mg), and all the patients reached the state of peripheral blood B cells clearance (CD19 + B cell count was<5/μl). After the first treatment of rituximab, the median time to B-cell clearance was 21(15, 35) days, and 8 patients reached B-cell depletion (CD19 + B cell count was 0). The remission rate was 12/13 (two cases reached complete remission, and 10 cases reached partial remission). Three cases stopped dialysis, and 1 case (with glomerulosclerosis of 52.94%) entered maintaining dialysis. The relapse times in the maintenance remission period of 7 patients with refractory lupus nephritis declined significantly from (1.57±0.53) times in a median history of 60(20, 109) months to (0.43±0.79) times in a median history of 18(10, 23) months after the use of rituximab ( P=0.015). After using rituximab, the incidence of infection was 7/13. The median time from the use of rituximab to infection was 26(4, 44) days. Pulmonary infection (5/13) was the most common type and all infected patients recovered after anti-infection treatment. Conclusions:Rituximab can be used in the treatment of active lupus nephritis with AKI, especially in patients with crescent formation and TMA, but the infection should be paid close attention to and prevented.