ObjectiveTo investigate the independent predictive factors for 90-day mortality in patients with acute-on-chronic liver failure （ACLF）， to establish a risk predictive model， and to assess its predictive efficacy in comparison with MELD， MELD-Na， MELD 3.0， and COSSH-ACLF Ⅱ. MethodsA retrospective analysis was performed for the clinical data of 394 patients with ACLF who were admitted to The Affiliated Hospital of Inner Mongolia Medical University and Hohhot Second Hospital from July 2018 to July 2024， and general information and laboratory markers on admission were collected from all patients. The independent-samples t test or the Mann-Whitney U test was used for comparison of quantitative data between two groups， and the chi-square test or the adjusted chi-square test was used for comparison of qualitative data between two groups. The LASSO regression analysis was used to identify related variables， and the multivariate logistic regression analysis was used to establish a predictive model and generate a nomogram. The receiver operating characteristic （ROC） curve， the area under the ROC curve （AUC）， calibration curve， and clinical decision curve were used to assess the performance of the model. ResultsA total of 394 patients with ACLF were included in this study， with 136 patients in the training set， 58 in the internal validation set， and 200 in the external validation set. The cohort had a mean age of 52.9±11.7 years， among whom male patients accounted for 72.84% （287/394）， the patients with HBV infection accounted for 22.33% （88/394）， the patients with alcohol-related causes accounted for 45.94% （181/394）， and the patients with other causes （including drug-induced and autoimmune diseases） accounted for 31.73% （125/394）. The overall 90-day mortality rate was 27.41% （108/394）. The multivariate logistic regression analysis showed that diabetes （odds ratio ［OR］= 5.831， 95% confidence interval ［CI］： 1.587 — 21.424， P=0.008）， cystatin C （Cys-C） （OR=2.984， 95%CI： 1.501 — 5.933， P=0.002）， and spontaneous peritonitis （SBP） （OR=5.692， 95%CI： 2.150 — 15.071， P<0.001） were independent risk factors， and a nomogram was generated based on these factors. This model had an AUC of 0.836 in the training set， 0.881 in the internal validation set， and 0.878 in the external validation set， showing a good discriminatory ability. The calibration curve showed a good degree of fitting， with a relatively high net clinical benefit. The subgroup analysis based on etiology showed that the model had an AUC of 0.850 in the patients with HBV infection， 0.858 in the patients with alcohol-induced ACLF， and 0.908 in the patients with other etiologies， indicating that the model had a good discriminatory ability across the populations with different etiologies. Compared with traditional scores， the model （AUC=0.836） had a significantly better predictive value than MELD （AUC=0.619， Z=3.197， P=0.001）， MELD-Na （AUC=0.651， Z=2.998， P=0.003）， MELD 3.0 （AUC=0.601， Z=3.682， P<0.001）， and COSSH-ACLF Ⅱ （AUC=0.719， Z=2.396， P=0.017） alone. ConclusionDiabetes， SBP， and Cys-C are independent risk factors for 90-day mortality in patients with ACLF. Compared with MELD， MELD-Na， MELD 3.0， and COSSH-ACLF Ⅱ scores， this model has a higher predictive value for 90-day prognosis in patients with ACLF and is suitable for patients with ACLF caused by various etiologies.

Investigator initiated trial （IIT） represents a primary format for clinical research in traditional Chinese medicine （TCM）. As key implementation sites for TCM-based IIT targeting malignant tumors， western medicine institutions often face unique challenges in conducting such studies， which limit their feasibility and standardization. This paper reviews the registration status of TCM-based IIT for malignancies conducted in western medical institutions and analyzes key difficulties， including complex project initiation and management processes， limited TCM knowledge and skills among western medicine physicians， and relatively low patient acceptance of TCM. From a practical perspective， the study proposes several optimization strategies. These include improving the review and management mechanisms of TCM-related IIT within western medical institutions， establishing multidisciplinary clinical research teams that integrate TCM and western medicine， and enhancing investigators' training in TCM theory and clinical skills. Additionally， the study suggests standardizing IIT operational procedures， objectifying the collection of TCM diagnostic information， refining subject recruitment methods， and increasing TCM involvement in patient follow-up and management. These investigator-oriented， TCM-featured， and operable strategies aim to promote the high-quality development of TCM-based IIT in western medicine institutions and enhance the clinical application of TCM.

Objective To investigate the correlation of solute carrier protein 17 family member 1 (SLC17A1) gene single nucleotide polymorphisms (SNPs) and susceptibility to hyperuricemia (HUA) in automotive manufacturing workers. Methods A total of 192 Han male workers diagnosed with HUA were selected as the case group, 192 Han male workers without HUA from the same enterprises were selected as the control group. These workers were determined by the matching factor of age, total length of service, and body mass index by the 1∶1 case-control study method. Peripheral venous blood from the workers was collected for DNA extraction. Two SNPs of SLC17A1 were genotyped by MassArray system. Results The gene frequency distributions of SLC17A1 rs2096386 and rs1183201 of workers in the control group were in consistent with the Hardy-Weinberg equilibrium test (both P>0.05). The allele frequency distribution of rs2096386, and the genotype and allele frequency distribution of rs1183201 were significantly different between workers in the two groups (all P<0.05). There was no significant difference in genotype frequency distribution of rs2096386 between workers in the two groups (P>0.05). The results of conditional logistic regression analysis showed that workers with G allele at rs2096386 increased the risk of HUA [odds ratio (OR)=1.43, 95% confidence interval (CI)=1.01-2.04], workers with T allele at rs1183201 increased the risk of HUA (OR=2.03, 95%CI =1.29-3.19), after adjusting for confounding factors such as serum creatinine, blood urea nitrogen, alanin aminotransferase and aspartate aminotransferase. While workers with TA and TA+AA genotypes at rs1183201 had a lower risk of HUA than those with TT genotype (OR=0.51, 95%CI =0.30-0.85; OR=0.50, 95%CI =0.30-0.83), workers with TA genotype at rs1183201 had a lower risk of HUA than those with TT+AA genotype (OR=0.53, 95%CI =0.32-0.88). Conclusion The polymorphisms at rs2096386 and rs1183201 of SLC17A1 gene may be correlated with HUA susceptibility among automobile manufacturing workers in Guangzhou City.

Objective To quantitatively assess the association of short-term exposure to polycyclic aromatic hydrocarbons (PAHs) in ambient fine particulate matter (PM2.5) with residents mortality. Methods A time-stratified case-crossover study was conducted from 2020 to 2022 among 10606 non-accidental residents by using the Guangzhou Cause of Death Surveillance System in Conghua District, Guangzhou. Exposure levels of PAHs in PM_2.5 and meteorological data during the study period were obtained from the Center for Disease Control and Prevention in Conghua District and the China Meteorological Administration Land Data Assimilation System (CLDAS-V2.0), respectively. Conditional Poisson regression model was used to estimate the exposure-response association between PAHs and the mortality risk. Results Fluoranthene, chrysene, benzo[k]fluoranthene, benzo[a]pyrene, and indeno[1,2,3-cd]pyrene were significantly associated with an increased risk of mortality. For every one interquartile range increase in exposure levels, the non-accidental mortality risks increased by 8.33% (95% CI: 1.80%, 15.27%), 4.67% (95% CI: 1.86%, 7.57%), 6.07% (95% CI: 2.08%, 10.21%), 4.62% (95% CI: 1.85%, 7.47%), and 4.70% (95% CI: 0.53%, 9.03%), respectively. The estimated non accidental deaths attributable to exposure to fluoranthene, chrysene, benzo[k]fluorine, benzo[a]pyrene and indine[1,2,3-cd]pyrene were 5.91%, 6.08%, 6.51%, 6.46%, and 4.21%, respectively. Conclusions Short-term exposure to PAHs in PM_2.5, including fluoranthene, chrysene, benzo[k]fluoranthene, benzo[a]pyrene and indine[1,2,3-cd]pyrene, was significantly associated with an increased risk of mortality among residents.

OBJECTIVES: To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice. METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining. RESULTS: After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups. CONCLUSIONS Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
Animals ; Periodontitis/microbiology* ; Mice ; Mice, Inbred C57BL ; Cognition ; Alveolar Bone Loss ; Hippocampus/pathology* ; Male ; Inflammation ; Maze Learning

Background Exposure to air pollutants increases the risk of diseases in multiple systems, including respiratory and cardiovascular systems, yet its association with neurological diseases remains unclear. Objective To quantitatively evaluate the association between short-term exposure to air pollutants and outpatient and emergency visits for neurological diseases, identify potential susceptible populations, and quantify associated disease burden. Methods Daily 24-hour average concentrations of fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and carbon monoxide (CO), daily maximum 8-hour average concentration of ozone (O₃), daily meteorological data (24-hour average temperature, 24-hour average relative humidity), and data on daily outpatient and emergency department visits for neurological diseases from two hospitals in Conghua District, Guangzhou, China, were collected from 2015 to 2022. A time-stratified case-crossover design was adopted, and a conditional Poisson regression model was constructed to analyze the association between air pollution exposure and neurological disease visits. Two-pollutant models and sensitivity analysis were used to validate model stability. Stratified analyses by season (cold season: from November to March; warm season: from April to October), sex (male, female), and age (≤45 years, 46–60 years, ≥61 years) were performed to identify vulnerable group. Additionally, the number and proportion of neurological disease visits attributable to short-term air pollutant exposure were calculated. Results A total of 72 673 outpatient and emergency department visits for neurological diseases were included during the study period. Most of the patients were middle-aged and elderly individuals (69.89% were over 45 years old) and females (60.25%). The results of single-pollutant models showed that for each interquartile range (IQR) increase in exposure to PM_2.5, PM₁₀, SO₂, NO₂, CO, and O₃, the risk of outpatient and emergency department visits for neurological diseases increased by 7.54% (95%CI: 4.69%, 10.46%), 6.66% (95%CI: 3.92%, 9.46%), 16.72% (95%CI: 10.58%, 23.19%), 8.12% (95%CI: 4.82%, 11.53%), 5.60% (95%CI: 2.34%, 8.97%), and 6.11% (95%CI: 2.91%, 9.40%), respectively. The results of the two-pollutant model showed that the association between PM_2.5 and SO₂ exposure and outpatient and emergency department visits for neurological diseases were relatively stable. The stratified analyses showed that the effect of SO₂ was stronger in the cold season. It was estimated that 8.32% (95%CI: 5.55%, 10.96%) and 6.65% (95%CI: 4.27%, 8.96%) of the outpatient and emergency department visits were attributable to short-term exposure to SO₂ and PM_2.5, respectively. Conclusion Exposure to PM_2.5 and SO₂ is associated with increased risks of outpatient and emergency visits for neurological diseases. SO₂ shows stronger effects during the cold season, and exposure to air pollution contributes to up to 8.32% of neurological disease visits.

Objective:To explore the effect of the absent in melanoma 2 (AIM2) -mediated neuroinflammation in noise-induced cognitive dysfunction in rats.Methods:In April 2023, sixteen male Wistar rats were randomly divided into control group and noise group, with 8 rats in each group. The rats in the noise group were placed in 50 cm×50 cm×40 cm transparent boxes and exposed to 100 dB (A) white noise with a sound pressure level of 100 dB (A) (4 h/d for 30 d) . At the same time, rats in the control group were kept in similar boxes with environmental noise less than 60 dB (A) . After 30 days of noise exposure, the Morris water maze experiment was applied to test the learning and memory abilities of the rats; the pathological morphology of hippocampal tissues was observed by Hematoxylin-Eosin (HE) staining. Western blot was used to detect the protein expression levels of AIM2, cysteinyl aspartate specific proteinase-1 (caspase-1) , apoptosis-associated speck-like protein (ASC) , interleukin-1β (IL-1β) , IL-18, ionic calcium-binding articulation molecule-1 (Iba-1) , and glial fibrillary acidic protein (GFAP) . The expression of both Iba-1 and GFAP in hippocampal tissue was assessed by immunohistochemical staining. The co-localization of AIM2 with Iba-1 or GFAP was determined by immunofluorescence double staining.Results:Compared with the control group, the escape latency of rats in the noise group was increased by 16.29 s, 17.71 s, and 20.26 s on days 3, 4, and 5, respectively. On day 6, the noise-exposed rats spent shorter time in the target quadrant and had fewer times in crossing the platform[ (7.25±2.27) s and (1.13±0.64) times] than the control group[ (15.64±3.99) s and (4.25±2.12) times] ( P<0.05) . After noise exposure, hippocampal neurons of rats displayed marked nuclear hyperchromatic and pyknosis phenomenon. The noise-exposed rats had higher numbers of both microglia and astrocytes (27.00±2.65 and 43.33±5.51) in the DG area of the hippocampus relative to the control group (14.67±3.06 and 20.00±4.58) ( P<0.05) . Moreover, the glial cells in the noise group had larger cell cytosol with more and thicker branches. The protein expression levels of inflammatory cytokines Cleaved-IL-1β and Cleaved-IL-18 in the hippocampus of rats in the noise group (1.55±0.19 and 1.74±0.12) were significantly higher than the control group (1.00±0.11 and 1.00±0.13) ( P<0.05) . After noise exposure, the protein expression levels of AIM2, Cleaved-Caspase-1 and ASC (1.19±0.09, 1.34±0.07 and 1.14±0.01) were higher than the control group (1.00±0.07, 1.00±0.14 and 1.00±0.06) and differences between the two groups were statistically significant ( P<0.05) . A significant increase in the number of cells co-localizing AIM2 with Iba-1 or GFAP in the noise group (28.67±4.04 and 40.67±5.13) compared with the control group (15.67±4.04 and 17.67±3.79) , and statistically significant differences were observed between the two groups ( P<0.05) . Conclusion:Noise exposure may activate the AIM2 inflammasome in hippocampal glial cells of rats, releasing excessive inflammatory cytokines and causing neuroinflammation that damages neurons.

Objective:To explore the effect of the absent in melanoma 2 (AIM2) -mediated neuroinflammation in noise-induced cognitive dysfunction in rats.Methods:In April 2023, sixteen male Wistar rats were randomly divided into control group and noise group, with 8 rats in each group. The rats in the noise group were placed in 50 cm×50 cm×40 cm transparent boxes and exposed to 100 dB (A) white noise with a sound pressure level of 100 dB (A) (4 h/d for 30 d) . At the same time, rats in the control group were kept in similar boxes with environmental noise less than 60 dB (A) . After 30 days of noise exposure, the Morris water maze experiment was applied to test the learning and memory abilities of the rats; the pathological morphology of hippocampal tissues was observed by Hematoxylin-Eosin (HE) staining. Western blot was used to detect the protein expression levels of AIM2, cysteinyl aspartate specific proteinase-1 (caspase-1) , apoptosis-associated speck-like protein (ASC) , interleukin-1β (IL-1β) , IL-18, ionic calcium-binding articulation molecule-1 (Iba-1) , and glial fibrillary acidic protein (GFAP) . The expression of both Iba-1 and GFAP in hippocampal tissue was assessed by immunohistochemical staining. The co-localization of AIM2 with Iba-1 or GFAP was determined by immunofluorescence double staining.Results:Compared with the control group, the escape latency of rats in the noise group was increased by 16.29 s, 17.71 s, and 20.26 s on days 3, 4, and 5, respectively. On day 6, the noise-exposed rats spent shorter time in the target quadrant and had fewer times in crossing the platform[ (7.25±2.27) s and (1.13±0.64) times] than the control group[ (15.64±3.99) s and (4.25±2.12) times] ( P<0.05) . After noise exposure, hippocampal neurons of rats displayed marked nuclear hyperchromatic and pyknosis phenomenon. The noise-exposed rats had higher numbers of both microglia and astrocytes (27.00±2.65 and 43.33±5.51) in the DG area of the hippocampus relative to the control group (14.67±3.06 and 20.00±4.58) ( P<0.05) . Moreover, the glial cells in the noise group had larger cell cytosol with more and thicker branches. The protein expression levels of inflammatory cytokines Cleaved-IL-1β and Cleaved-IL-18 in the hippocampus of rats in the noise group (1.55±0.19 and 1.74±0.12) were significantly higher than the control group (1.00±0.11 and 1.00±0.13) ( P<0.05) . After noise exposure, the protein expression levels of AIM2, Cleaved-Caspase-1 and ASC (1.19±0.09, 1.34±0.07 and 1.14±0.01) were higher than the control group (1.00±0.07, 1.00±0.14 and 1.00±0.06) and differences between the two groups were statistically significant ( P<0.05) . A significant increase in the number of cells co-localizing AIM2 with Iba-1 or GFAP in the noise group (28.67±4.04 and 40.67±5.13) compared with the control group (15.67±4.04 and 17.67±3.79) , and statistically significant differences were observed between the two groups ( P<0.05) . Conclusion:Noise exposure may activate the AIM2 inflammasome in hippocampal glial cells of rats, releasing excessive inflammatory cytokines and causing neuroinflammation that damages neurons.

This study aimed to investigate the differences in peripheral blood lymphocyte subsets among patients with different immune statuses in the early postoperative period after liver transplantation, as well as the dynamic changes during the early post-transplantation period. A retrospective study was conducted, selecting a total of 82 patients who underwent liver transplantation at the General Hospital of PLA Southern Theater Command from January, 2018 to December, 2023. Based on the patients′ postoperative immune status, they were categorized into stable group ( n=40), infection group ( n=21), and rejection group ( n=21). Peripheral blood samples of 2-3 ml were collected from patients at weeks 1 to 4 postoperatively, and flow cytometry was employed to measure the absolute values of peripheral blood lymphocyte subsets. For metric data conforming to normal distribution and homogeneity of variance, multiple group comparisons were conducted using ANOVA and Bonferroni multiple comparisons; for non-normally distributed data, the Kruskal Wallis test was used. Friedman test was used to compare different time periods within 4 weeks after liver transplantation. The results showed that there were no statistically significant differences in the absolute values of lymphocyte subsets among the three groups in the first week after liver transplantation ( P>0.05); however, significant differences were observed in the absolute values of lymphocyte subsets among the three groups in the second, third, and fourth weeks postoperatively ( P<0.05). In the second week, the rejection group showed significantly higher absolute counts of T cells, CD4 +T cells, CD8 +T cells, NK cells, and B cells compared to the infection group (585.0 vs. 199.0; 324.0 vs.113.0; 188.0 vs.56.0; 57.0 vs.11.0; 145.0 vs.65.0 cells/μl), with statistically significant differences ( Z=-3.972, P<0.001; Z=-3.590, P=0.001; Z=-3.978, P<0.001; Z=-3.072, P=0.006; Z=-2.472, P=0.040). In the third week, the rejection group showed significantly higher absolute counts of T cells, CD4 +T cells, and CD8 +T cells compared to the infection group (660.0 vs.216.0; 350.0 vs.123.0; 184.0 vs.76.0 cells/μl), with statistically significant differences ( Z=-3.019, P=0.008; Z=-3.492, P=0.001; Z=-2.845, P=0.013). In the fourth week, the rejection group showed significantly higher absolute counts of T cells, CD4 +T cells, CD8 +T cells, and B cells compared to the infection group (690.0 vs.273.0; 405.0 vs.168.0; 214.0 vs.96.0; 117.0 vs.48.0 cells/μl), with statistically significant differences ( Z=-3.379, P=0.002; Z=-3.068, P=0.006; Z=-3.007, P=0.0086; Z=-2.330, P=0.020). Within 4 weeks after liver transplantation, the absolute values of T cells, CD8 +T cells, and NK cells in the fourth week were higher than those in the first week, with statistically significant differences ( Z=-3.825, P=0.001; Z=-3.466, P=0.003; Z=-3.526, P=0.003); however, the absolute values of B cells showed an overall decreasing trend, and were significantly lower in the fourth week than in the first and second weeks, with statistically significant differences ( Z=3.705, P=0.001; Z=2.630, P=0.009). The changes in lymphocyte subset absolute values in the rejection group were more significant than those in the infection group, with T cells, CD4 +T cells, and CD8 +T cells showing significant increases in the second, third, and fourth weeks postoperatively compared with the first week, with statistically significant differences ( Z=-3.466, P=0.003; Z=-4.661, P<0.001; Z=-5.020, P<0.001; Z=-2.749, P=0.036; Z=-4.422, P<0.001; Z=-4.542, P<0.001; Z=-3.466, P=0.003; Z=-3.765, P=0.001; Z=-4.482, P<0.001); NK cell absolute values in the third and fourth weeks postoperatively were significantly higher than those in the first week, with statistically significant differences ( Z=-2.570, P=0.061; Z=-3.765, P=0.001). In summary, monitoring the differences and dynamic changes of lymphocyte subsets in patients after liver transplantation may have certain guiding significance for evaluating the immune function status of patients and adjusting treatment plans.

Objective:To investigate the short-term efficacy and safety of cardiac contractility modulation (CCM) in patients with heart failure.Methods:This was a cross-sectional study of patients with heart failure who underwent CCM placement at the First Affiliated Hospital of Xinjiang Medical University from February to June 2022. With a follow-up of 3 months, CCM sensation, impedance, percent output, and work time were monitored, and patients were compared with pre-and 3-month postoperative left ventricular ejection fraction (LVEF) values, and 6-minute walk test distance and New York Heart Association (NYHA) cardiac function classification, and the occurrence of complications was recorded.Results:CCM was successfully implanted in all 9 patients. Seven(7/9) of them were male, aged (56±14) years, 3 patients had ischaemic cardiomyopathy and 6 patients had dilated cardiomyopathy. At 3-month postoperative follow-up, threshold was stable, sense was significantly lower at follow-up than before (right ventricle: (16.3±7.0) mV vs. (8.2±1.1) mV, P<0.05; local sense: (15.7±4.9) mV vs. (6.7±2.5) mV, P<0.05), and impedance was significantly lower at follow-up than before (right ventricle (846±179) Ω vs. (470±65) Ω, P<0.05, local sense: (832±246) Ω vs. (464±63) Ω, P<0.05). The CCM output percentage was (86.9±10.7) %, the output amplitude was (6.7±0.4) V, and the daily operating time was (8.6±1.0) h. LVEF was elevated compared to preoperative ((29.4±5.2) % vs. (38.3±4.3) %, P<0.05), the 6-minute walk test was significantly longer than before ((96.8±66.7)m vs. (289.3±121.7)m, P<0.05). No significant increase in the number of NYHA Class Ⅲ-Ⅳ patients was seen (7/9 vs. 2/9, P>0.05). The patient was not re-hospitalised for worsening heart failure symptoms, had no malignant arrhythmic events and experienced significant relief of symptoms such as chest tightness and shortness of breath. No postoperative complications related to pocket hematoma, pocket infection and rupture, electrode detachment, valve function impairment, pericardial effusion, or cardiac perforation were found. Conclusions:CCM has better short-term safety and efficacy in patients with heart failure.