Objective: To develop a prediction model for mild cognitive impairment (MCI) risk among the elderly, so as to provide a tool for MCI early screening. Methods : From July 2022 to September 2024, a multi-stage stratified random cluster sampling method was used to recruit permanent residents aged ≥65 years from the Xinjiang Uygur Autonomous Region as study participants. Data on sociodemographic characteristics, nutritional status, body composition indices, bone mineral density, and handgrip strength were collected through questionnaires and physical examinations. Sarcopenia was defined based on appendicular skeletal muscle index and handgrip strength. MCI was assessed using the Mini-Mental State Examination, with adjustments for educational level. Participants were randomly divided into a training set and a validation set in a 7∶3 ratio. LASSO regression and multivariable logistic regression models were employed to screen for predictors and construct an MCI risk prediction model. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results: A total of 1 641 participants were surveyed, including 755 males (46.01%) and 886 females (53.99%). The majority of participants were aged 65-<75 years, comprising 1 154 individuals (70.32%). MCI was detected in 517 participants, corresponding to a detection rate of 31.51%. Resultsfrom LASSO regression and multivariate logistic regression analysis showed that residence (rural, OR = 2.323, 95% CI: 1.682-3.210), age (75-<85 years, OR = 1.405, 95% CI: 1.019-1.937; ≥85 years, OR = 3.655, 95% CI: 1.696-7.875), educational level (primary school, OR = 0.341, 95% CI: 0.247-0.472; junior high school, OR = 0.255, 95% CI: 0.160-0.408; high school, OR = 0.286, 95% CI: 0.154-0.531; bachelor's degree or above, OR = 0.120, 95% CI: 0.041-0.351), history of alcohol consumption (yes, OR = 3.216, 95% CI: 2.164-4.779), risk of malnutrition (yes, OR = 1.464, 95% CI: 1.064-2.014), sarcopenia (yes, OR = 3.197, 95% CI: 2.332-4.385), and waist-to-hip ratio (abnormal, OR = 1.540, 95% CI: 1.159-2.048) were identified as predictive factors for MCI among the elderly. In the training set, the area under the ROC curve, sensitivity, and specificity were 0.788, 0.719, and 0.712, respectively. In the validation set, the corresponding values were 0.784, 0.913, and 0.542, respectively. DCA demonstrated that the model provided a higher clinical net benefit for predicting MCI risk when the risk threshold probability ranged from 0.124 to 0.764. Conclusion The prediction model developed in this study demonstrates good discriminative ability and clinical utility, indicating its substantial value for predicting the MCI risk among the elderly.

Neurosyphilis is a group of clinical syndromes caused by treponema pallidum invading the central nervous system and causing varying degrees of damage to the brain parenchyma, brain (spinal) membrane or spinal cord. Cerebral syphilitic gumma is the rarest form of neurosyphilis, and its clinical manifestations lack specificity, which is easily confused with other intracranial space occupying lesions on imaging. In this article, a patient with cognitive dysfunction, intracranial hypertension, and imaging findings similar to multicentric glioma was diagnosed as cerebral syphilitic gumma by serology, cerebrospinal fluid test and brain histopathology. The symptoms basically disappeared after treatment with standard penicillin. This report aims to raise awareness of cerebral syphilitic gumma in order to reduce missed diagnosis and misdiagnosis.

Neurosyphilis is a group of clinical syndromes caused by treponema pallidum invading the central nervous system and causing varying degrees of damage to the brain parenchyma, brain (spinal) membrane or spinal cord. Cerebral syphilitic gumma is the rarest form of neurosyphilis, and its clinical manifestations lack specificity, which is easily confused with other intracranial space occupying lesions on imaging. In this article, a patient with cognitive dysfunction, intracranial hypertension, and imaging findings similar to multicentric glioma was diagnosed as cerebral syphilitic gumma by serology, cerebrospinal fluid test and brain histopathology. The symptoms basically disappeared after treatment with standard penicillin. This report aims to raise awareness of cerebral syphilitic gumma in order to reduce missed diagnosis and misdiagnosis.

ObjectiveTo investigate the mechanism of Ershiwuwei Guijiu pill in preventing and treating postmenopausal osteoporosis （PMOP） by activating the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway and inhibiting excessive autophagy. MethodFemale SD rats were ovariectomized and randomly divided into the sham operation group （Sham）， the operation group （OVX）， the Ershiwuwei Guijiu pill （GJ） group， and the raloxifene hydrochloride （RLX） group， with 10 rats in each group. Enzyme-linked immunosorbent assay （ELISA） and colorimetric methods were used to detect the levels of estrogen， bone metabolism markers in serum， and total superoxide dismutase （T-SOD）， malondialdehyde （MDA）， and glutathione peroxidase （GSH-Px） in tibial tissue. Flow cytometry was used to detect reactive oxygen species （ROS） levels in bone marrow mesenchymal stem cells. Masson staining was used to observe pathological changes in the proximal tibia， and micro-computed tomography （Micro-CT） was used to observe changes in tibial microstructural parameters. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of autophagy-related proteins Beclin1， microtubule-associated protein 1A/1B-light chain 3 （LC3）， autophagy-related 5 （Atg5）， as well as PI3K， Akt， and mTOR in tibial tissue. ResultCompared with the Sham group， the OVX group showed a significant decrease in serum levels of estradiol （E₂） and calcium ion （Ca²⁺）， and T-SOD， GSH-Px， PI3K， Akt， and mTOR mRNA levels in bone tissue （P<0.05， P<0.01）， significantly reduced bone mineral density （BMD）， bone surface/bone volume （BS/BV）， trabecular thickness （Tb.Th）， trabecular number （Tb.N）， and trabecular connectivity （Con） in the tibia （P<0.05， P<0.01）， thinner epiphyseal growth plate， and the bone marrow cavity filled with fat vacuoles. Moreover， the levels of phosphorus （P）， MDA， ROS， and mRNA and protein expression of Beclin1， LC3， and Atg5， as well as trabecular separation （Tb.Sp） were significantly elevated （P<0.05， P<0.01）. Compared with the OVX group， the GJ and RLX groups showed significant increases in serum E₂ and Ca²⁺， and bone tissue levels of SOD， GSH-Px， and the mRNA levels of PI3K， Akt， and mTOR （P<0.05， P<0.01）， significantly increased BMD， BS/BV， Tb.Th， Tb.N， and Con in the tibia， thickened epiphyseal growth plate， and significantly reduced fat vacuoles in the bone marrow cavity （P<0.05， P<0.01）. Additionally， the levels of P， MDA， ROS， Beclin1， LC3， Atg5 mRNA and proteins， and Tb.Sp were significantly decreased （P<0.05， P<0.01）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR， which were significantly reduced in the OVX group （P<0.01）， were significantly increased in the GJ and RLX groups （P<0.01）. ConclusionThe Ershiwuwei Guijiu pill reduces oxidative stress and inhibits autophagy， thereby preventing and treating postmenopausal osteoporosis. Its mechanism may be related to the activation of the PI3K/Akt/mTOR signaling pathway， which inhibits autophagy.

In recent years, immune checkpoint inhibitors (ICIs) have made great progress in the treatment of tumor patients, prolonging their survival. However, the expansion of immunity against tumors with ICIs may also cause an imbalance in immune tolerance, leading to immune-related adverse events (irAEs). Immune-mediated liver injury caused by ICIs (ILICI) is one of the more common types of irAEs. In this review paper, the definition, epidemiology, risk factors, pathogenesis, pathology, clinical manifestations, treatment, recurrence, and re-treatment of ILICI were summarized to provide a basis for clinical diagnosis and treatment.

‍ ObjectiveTo investigate the value of preoperative fibrosis 4 score （FIB-4） combined with prognostic nutritional index （PNI） in predicting recurrence after radiofrequency ablation （RFA） for early-stage hepatocellular carcinoma （HCC）. MethodsA retrospective analysis was performed for the clinical data of 365 patients with the initial diagnosis of early-stage HCC who underwent RFA at Tianjin Third Central Hospital from January 2013 to December 2017， and a statistical analysis was performed for recurrence and survival. The receiver operating characteristic （ROC） curve was plotted for FIB-4 and PNI with postoperative tumor recurrence as the positive event， and their optimal cut-off values were selected. FIB-4 and PNI were graded and combined as FIB-4-PNI score， based on which the patients were divided into 0-point group with 207 patients， 1-point group with 93 patients， and 2-point group with 65 patients. The chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier survival analysis and the log-rank test were used to compare the recurrence-free survival （RFS） and overall survival （OS） between groups， and the Cox regression model was used to investigate the influencing factors for RFS and OS. ResultsThe 1-， 3-， and 5-year RFS rates of all patients were 79.2%， 49.8%， and 34.3%， respectively， with a median RFS of 35 months， while the 1-， 3-， and 5-year OS rates of all patients were 98.9%， 86.9%， and 77.3%， respectively. There were significant differences in cumulative RFS and OS rates between the patients with different levels of FIB-4， PNI， and FIB-4-PNI （RFS rate： χ²=17.890， 29.826， and 32.397， all P<0.001； OS rate： χ²=16.896， 21.070， and 26.121， all P<0.001）. The multivariate Cox regression analysis showed that history of diabetes （hazard ratio ［HR］=1.418， 95% confidence interval ［CI］： 1.046‍ ‍—‍ ‍1.922， P=0.024）， two tumors （HR=1.516， 95%CI： 1.094‍ ‍—‍ ‍2.101， P=0.012）， three tumors （HR=2.146， 95%CI： 1.278‍ ‍—‍ ‍3.604， P=0.004）， FIB-4-PNI 1 point （HR=1.875， 95%CI： 1.385‍ ‍—‍ ‍2.539， P<0.001）， and FIB-4-PNI 2 points （HR=2.35， 95%CI： 1.706‍ ‍—‍ ‍3.236， P<0.001） were independent risk factors for RFS， while two tumors （HR=1.732， 95%CI： 1.005‍ ‍—‍ ‍2.983， P=0.048）， three tumors （HR=3.511， 95%CI： 1.658‍ ‍—‍ ‍7.433， P=0.001）， FIB-4-PNI 1 point （HR=2.094， 95%CI： 1.230‍ ‍—‍ ‍3.565， P=0.006）， and FIB-4-PNI 2 points （HR=3.908， 95%CI： 2.306‍ ‍—‍ ‍6.624， P<0.001） were independent risk factors for OS. ConclusionFIB-4-PNI score can be used as an independent predictive factor for recurrence and overall survival time after RFA for early-stage HCC， and it can be combined with tumor features to predict postoperative recurrence and survival.

Objective To investigate the clinical effect of direct-acting antiviral agent (DAA) in the treatment of chronic hepatitis C (CHC) patients with thrombocytopenia and its effect on platelet count (PLT). Methods A retrospective analysis was performed for 83 CHC patients with thrombocytopenia (PLT < 150×10 9 /L) who received the DAA treatment regimen without interferon for 12-24 weeks in Tianjin Third Central Hospital from April 2018 to March 2019, and the changes in virologic response, liver function parameters, PLT, and liver stiffness measurement (LSM) were evaluated at the end of treatment (EOT) and at week 12 after EOT. Quantitative data accord with normal distribution were compared by repeated measures ANOVA. Normal transformation was performed before the comparison between skewed data, then repeated measures ANOVA was carried out. A logistic regression analysis was used to investigate the predictive factors for PLT elevation, and the receiver operating characteristic (ROC) curve was plotted to analyze the value of LSM in predicting PLT elevation after treatment. Results Among the 83 CHC patients with thrombocytopenia, 61.4% had liver cirrhosis, and the rate of sustained virologic response at week 12 after the end of treatment (SVR12) was 98.8%. From baseline to EOT and SVR12, the patients had significant reductions in the serum levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, total bilirubin, and globin, a significant increase in the serum level of albumin, and a significant reduction in LSM (all P < 0.05). For all patients, PLT at EOT and SVR12 was significantly higher than that at baseline [EOT vs baseline: (110.4±44.6)×10 9 /L vs (97.8±33.2)×10 9 /L, P < 0.01; SVR12 vs baseline: (109.0±47.7)×10 9 /L vs (97.8±33.2)×10 9 /L, P < 0.01]. At SVR12, there were significant differences in the proportion of patients with liver cirrhosis, baseline LSM, and baseline white blood cell count between the PLT elevation group and the non-PLT elevation group (all P < 0.05). The multivariate logistic regression analysis showed that LSM was an independent predictive factor for significant PLT elevation after DAA treatment (odds ratio=0.929, 95% confidence interval: 0.864-0.999, P < 0.05). Baseline LSM had an area under the ROC curve of 0.644 in predicting PLT elevation, with a sensitivity of 81.0% and a specificity of 48.6% at a cut-off value of 20.15 kPa. The patients with PLT > 100×10 9 /L at baseline had a greater increase in PLT( P < 0.05). Conclusion CHC patients with thrombocytopenia have significant improvements in liver function and LSM after receiving DAA treatment and obtaining SVR12, and baseline LSM is an independent predictive factor for PLT elevation. There is a significant increase in PLT from baseline to EOT and SVR12.

Objective To investigate the level of glycosylated albumin (GA) in liver cirrhosis patients with different Child-Pugh classes and its application value in predicting liver function. Methods A total of 486 patients with liver cirrhosis who were hospitalized in Tianjin Third Central Hospital from January 1 to December 31, 2019, were enrolled, among whom 227 patients had liver cirrhosis without diabetes and 259 patients had liver cirrhosis with diabetes. The patients were divided into groups according to Child-Turcotte-Pugh (CTP) score, and fasting blood glucose, glycosylated hemoglobin, and percentage of GA (GA%) were measured. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between three groups, and the Dwass-Steel-Critchlow-Fligner test was used for further comparison between two groups. Scatter plots and fitting curves were plotted for CTP score and GA% to evaluate the association between them and calculate the cut-off value. Results For the cirrhosis patients without diabetes, there were significant differences between the patients with different Child-Pugh classes in GA% ( χ 2 =24.809, P < 0.001), fasting blood glucose ( χ 2 =11.899, P =0.003), and glycosylated hemoglobin ( χ 2 =13.607, P =0.001); further pairwise comparison showed that there was a significant difference in GA% between Child-Pugh class A/B liver cirrhosis patients without diabetes and Child-Pugh class C liver cirrhosis patients ( P < 0.05), Child-Pugh class A patients had a significantly higher level of fasting blood glucose than Child-Pugh class B patients ( P < 0.05), and Child-Pugh class A patients had a significantly higher level of glycosylated hemoglobin than Child-Pugh class B/C patients ( P < 0.05). For the patients with liver cirrhosis and diabetes, there were significant differences between the patients with different Child-Pugh classes in GA% ( χ 2 =10.734, P =0.005) and fasting blood glucose ( χ 2 =16.295, P < 0.001); further pairwise comparison showed that Child-Pugh class C liver cirrhosis patients with diabetes had a significantly lower GA% than Child-Pugh class A/B patients ( P < 0.05) and Child-Pugh class A patients had a significantly lower fasting blood glucose level than Child-Pugh class B patients ( P < 0.05). The fitting curve showed that GA% increased with the increase in CTP score in the liver cirrhosis patients without diabetes, reached the highest value at the CTP score of 6.5, and then started to decrease, with the lower value at the CTP score of 11.5, which showed a curvilinear relationship; in the liver cirrhosis patients with diabetes, GA% first increased and then decreased with the increase in CTP score, with a cut-off value of 8. Conclusion GA% first increases and then decreases along with the progression of liver cirrhosis. There is a significant difference in GA between liver cirrhosis patients with different Child-Pugh classes, suggesting that the reduction in GA is closely associated with liver function decompensation in end-stage liver cirrhosis.

Wnt5a is a secreted Wnt ligand that plays a critical role in cellular pathways and inflammatory diseases. The WNT5A gene encodes two protein isoforms, Wnt5a-long and Wnt5a-short, which differ based on different promoter methylation and have distinct functions. However, the mechanisms of the promoter methylation are unclear. Depending on the extent of promoter methylation, Wnt5a exerts both anti-inflammatory and pro-inflammatory effects in inflammatory diseases, which may be involved in different Wnt5a isoforms. Therefore, the Wnt5a isoforms may be potential diagnostic markers for inflammatory diseases and the mechanisms of the WNT5A gene promoter methylation need to be further investigated.
DNA Methylation ; Wnt-5a Protein ; Promoter Regions, Genetic ; Protein Isoforms/genetics*

Objective:To analyze the risk factors of death within two years of the patients with liver cirrhosis after transjugular intrahepatic portosystemic shunt(TIPS), and to explore the predictive value of 6 common clinical evaluation systems on the risk of death after TIPS.Methods:TIPS clinical data from 132 patients with liver cirrhosis were analyzed retrospectively. According to the 2-year clinical outcome after TIPS, the patients were divided into the death group and the survival group. Logistic regression was used to analyze the risk factors of death within 2 years after TIPS. According to the scores of CTP, MELD, MELD Na, BioCliM, FIB-4, and ALBI evaluation systems, the prediction efficiency of death risk of the six evaluation systems was evaluated by using the receiver operating characteristic (ROC) curves and the area under the curve (AUC).Results:During the 2-year follow-up period after TIPS, the age, urea nitrogen level, platelet count, and proportion of hepatic encephalopathy in the death group were higher than those in the survival group one month after TIPS, and the serum sodium level was lower than those in the survival group (all P<0.05). Multivariate analysis showed that the elderly and hepatic encephalopathy one month after operation were independent risk factors for death (all P<0.05). At 1 week after the surgery, there were significant differences in CTP, MELD, and MELD-Na scores between the survival group and the death group (all P<0.05). One week after operation, the AUC of ROC of CTP, MELD, MELD-Na, and ALBI scores were 0.685, 0.721, 0.805, and 0.658 respectively, and the optimal critical values were 8.5, 12.99, 14.51 and -1.52 respectively. Conclusions:The elderly and the occurrence of hepatic encephalopathy one month after TIPS are independent risk factors for the death of liver cirrhosis patients after TIPS. The evaluation of CTP, MELD, MELD-Na, and ALBI one week after TIPS can predict the death risk of decompensated liver cirrhosis patients within 2 years after TIPS, and MELD-Na has the best predictive effect.