BACKGROUND:Ammonia poisoning is considered to be the main hypothesis for the pathogenesis of hepatic encephalopathy.Ammonia can lead to psychiatric and cognitive behavioral disorders,although the specific pathological molecular mechanisms remain unclear.OBJECTIVE:To investigate the effects of ammonia poisoning on cognitive behavior and hippocampal neuronal synapses in mice.METHODS:Thirty-two C57BL/6J mice were randomly divided into a normal control group and an ammonium chloride group,with 16 mice in each group.Normal saline was injected intraperitoneally in the control group,and ammonium chloride(10 mmol/kg)was injected intraperitoneally in the ammonium chloride group to construct a model of ammonia poisoning,once a day.After 7 days of ammonium chloride intervention,blood samples were collected from the hearts of six mice in each group for blood ammonia concentration detection.Behavioral experiments,including the open field test,novel object recognition test,and Y-maze test,were performed to assess mental and cognitive-behavioral changes in mice.Finally,hippocampal tissues were extracted for western blot analysis to detect the expression levels of synaptophysin and postsynaptic density protein-95 in hippocampal neurons.RESULTS AND CONCLUSION:The blood ammonia concentration was significantly elevated in the ammonium chloride group compared with the control group(P＜0.05).Mice in the ammonium chloride group showed anxiety-like behavior and disinhibition phenomenon,and a significant decrease in recognition memory and working memory ability.Western blot results revealed that the expression of synaptophysin and postsynaptic density protein-95 protein in hippocampal neurons in the ammonium chloride group was lower than that in the control group(P＜0.05).To conclude,ammonia poisoning can induce hippocampal neuronal synaptic damage,leading to psychiatric and cognitive behavioral abnormalities in mice.

BACKGROUND:Ammonia poisoning is considered to be the main hypothesis for the pathogenesis of hepatic encephalopathy.Ammonia can lead to psychiatric and cognitive behavioral disorders,although the specific pathological molecular mechanisms remain unclear.OBJECTIVE:To investigate the effects of ammonia poisoning on cognitive behavior and hippocampal neuronal synapses in mice.METHODS:Thirty-two C57BL/6J mice were randomly divided into a normal control group and an ammonium chloride group,with 16 mice in each group.Normal saline was injected intraperitoneally in the control group,and ammonium chloride(10 mmol/kg)was injected intraperitoneally in the ammonium chloride group to construct a model of ammonia poisoning,once a day.After 7 days of ammonium chloride intervention,blood samples were collected from the hearts of six mice in each group for blood ammonia concentration detection.Behavioral experiments,including the open field test,novel object recognition test,and Y-maze test,were performed to assess mental and cognitive-behavioral changes in mice.Finally,hippocampal tissues were extracted for western blot analysis to detect the expression levels of synaptophysin and postsynaptic density protein-95 in hippocampal neurons.RESULTS AND CONCLUSION:The blood ammonia concentration was significantly elevated in the ammonium chloride group compared with the control group(P＜0.05).Mice in the ammonium chloride group showed anxiety-like behavior and disinhibition phenomenon,and a significant decrease in recognition memory and working memory ability.Western blot results revealed that the expression of synaptophysin and postsynaptic density protein-95 protein in hippocampal neurons in the ammonium chloride group was lower than that in the control group(P＜0.05).To conclude,ammonia poisoning can induce hippocampal neuronal synaptic damage,leading to psychiatric and cognitive behavioral abnormalities in mice.

Objective:To investigate the efficacy of oral folic acid intervention in lung cancer patients with radiation esophagitis (RE) caused by concurrent chemoradiotherapy.Methods:In this randomized, controlled, single-center clinical trial, a total of 82 patients with stage N 2-N 3 lung cancer including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to October 2023 were prospectively included. All enrolled patients were randomly divided into the experimental group (folic acid group) and control group according to 1 vs. 1 of simple random method, and patients in both groups were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes [≥2 cycles of chemotherapy were completed during the same period of radiotherapy (≥40 Gy / 20 F) or targeted drugs were given simultaneously]. The severity of RE was evaluated using the modified common terminology criteria for adverse events criteria of the National Cancer Institute in both groups weekly at the onset of radiation esophagitis symptoms and thereafter until 1 week after the end of radiotherapy. Conventional treatment of RE was delivered according to the grading criteria of the Radiation Therapy Oncology Group. Patients in the folic acid group were given with folic acid tablets 30 mg/d orally at the beginning of radiotherapy until the end of radiotherapy, while those in the control group did not receive any drug intervention. The onset time, severity and duration of RE, and changes in the severity of esophageal toxicity after conventional treatment were recorded and analyzed. Serum folate value, serum vitamin B 12 value and homocysteine value were measured before and after radiotherapy. For continuous quantitative variables, independent sample t-test or independent sample rank-sum test was used for comparison among different groups. For categorical data, Chi-square test or Fisher's exact probability method was used for comparison among different groups. Results:During the observation period, no grade 4 or above RE was reported between two groups. The incidence of grade 0, 1, 2 and 3 RE in the folic acid and control groups was 10% (4/40) and 5% (2/41), 70% (28/40) and 42% (17/41), 15% (6/40) and 51% (21/41), 5% (2/40) and 2% (1/41), respectively. The differences were not statistically significant between two groups ( P=0.456). However, the incidence of grade 0-1 RE in the folic acid group was significantly higher than that in the control group ( Z=2.72, P=0.006). The median time of RE in the folic acid group and control group was 12 d (range 7-52 d) and 15 d (range 11-56 d) after the start of radiotherapy, respectively, with no statistically significant difference ( χ2=-0.75, P=0.456). However, median duration of the individual's most severe RE was 12 d (range 4-36 d) and 21 d (range 7-38 d) in the folic acid group and control groups, respectively, and the differences were statistically significant ( χ2=2.10, P=0.039). In the folic acid group, the grades of swallowing with pain and dysphagia were significantly declined after folic acid intervention, especially at 2 weeks after the occurrence of RE ( P=0.001, P=0.002). The remission rate of RE after 1 week in the folic acid group was higher than that in the control group, and the difference was statistically significant ( χ2=7.36, P=0.012). Conclusion:Oral intake of folic acid during concurrent chemoradiotherapy for lung cancer cannot reduce the incidence of RE, but it may reduce its severity, shorten the duration of the most severe RE in individuals, and have a certain protective effect.

Objective:To analyze the changes and significance in clinical cardiac indicators of early cardiac myocardial dysfunction and cardiac substructure dose during conventional radiotherapy for N 2-N 3 non-small cell lung cancer (NSCLC) with mediastinal lymph node metastases. Methods:The data of 34 NSCLC patients with lymph node metastases in regions 4-8 admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to August 2023 were observed and analyzed. All patients were treated with volumetric modulated arc therapy with a prescribed dose of 60-70 Gy. Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at 6 time points: within 1 week before radiotherapy ( t0); when the cumulative radiotherapy dose reaches 20 Gy ( t20), 40 Gy ( t40), 60 Gy ( t60) during radiotherapy; within 1 week after radiotherapy ( tp); 1 month after radiotherapy( tp1). Left ventricular global longitudinal strain (LVGLS) and left atrial global longitudinal strain (LAGLS) were assessed at 4 time points: t0, t40, tp and tp1, respectively. The changes in cardiac indicators at different time points during radiotherapy and their correlation with substructure doses were analyzed using analysis of variance, linear regression analysis, and Pearson correlation. Results:The correlation between cardiac substructure dose and mean heart dose (MHD) in the study cohort in the descending order was as follows: left ventricle ( B=0.43, P<0.001), right ventricle ( B=0.37, P=0.002), left atrium ( B=0.16, P<0.001), and right atrium ( B=0.15, P=0.001). There were significant differences in the changes of LVGLS and LAGLS across different time points ( F=3.13, P=0.029; F=17.18, P<0.001). At 1 month after radiation, LAGLS was significantly decreased compared to pre-radiation levels ( P=0.009), whereas no significant difference was observed in LVGLS ( P=1.000). No significant differences were observed in the changes of cTnT and NT-proBNP across different time points (all P>0.05). Significant correlations were identified between cTnT and right ventricle mean dose at t40 ( r=0.38, P=0.025), as well as between NT-proBNP and right atrium mean dose at t60 and tp ( r=0.54, P=0.001; r=0.41, P=0.016). Conclusions:At present, there is no significant difference between the sensitive serum markers of myocardial injury and LVGLS in detecting early myocardial injury. LAGLS may hold substantial clinical value. There is uncertainty about radiation injury and repair of various cardiac substructures.

Objective:To explore the effect of immobility on the quality of life in older adults.Methods:This cross-sectional study included 244 consecutive elderly patients aged 60 years and older who were admitted to the Department of Geriatrics at Xuanwu Hospital of Capital Medical University from May 2022 to March 2023.Among the participants, 52.5%(128/244)were male and 47.5%(116/244)were female, with a mean age of 69.2±7.4 years.All participants underwent a series of assessments, including the Short Physical Performance Battery(SPPB), grip strength measurement, gait speed evaluation, and the Timed Up and Go test(TUG).The Barthel Index was employed to assess activities of daily living, while the Medical Outcomes Study 36-Item Short Form Health Survey(SF-36)was used to evaluate quality of life.A score of SPPB ≤ 9 was used to diagnose immobility.Results:A total of 60 older adults met the criteria for immobility.Compared to the non-immobility group, the quality-of-life scores for older adults in the immobility group were significantly lower across various dimensions, including physical functioning, role-physical, bodily pain, general health, vitality, social functioning, physical component summary, and the total SF-36 score(all P<0.05).Furthermore, a positive correlation was identified between the SPPB scores and the quality-of-life scores across the dimensions of physical functioning, bodily pain, general health, vitality, social functioning, mental health, reported health transition, physical component summary, and the total SF-36 score among patients in the immobility group(all P<0.05).Additionally, older adults in the immobility group exhibited lower grip strength, slower gait speed, and longer TUG times, as well as a higher incidence of emergencies and falls over the past year(all P<0.05). Conclusions:The poorer quality of life and physical function, along with higher rates of emergencies and falls among older adults with immobility, indicate the necessity of addressing the health consequences that immobility inflicts on this population.

Objective To investigate factors that affect the treatment effect of laser vitrectomy for vit-reous opacity and the related factors that affect patient satisfaction,so as to evaluate its clinical value.Methods A total of 196 patients with vitreous opacity treated using the Ultra Q ReflexTM Nd:YAG laser system at our hospital between October 2019 and February 2024 were enrolled.Patient medical records and satisfaction questionnaires were analyzed.Investigational data underwent machine-coded classification,and a Python-based decision tree prediction model was employed to identify factors affecting treatment outcomes.Stata18.0 OLS linear regression was used to assess correlations between patient satisfaction and variables such as healthcare provider quality,treatment accessibility,and medical environment.Results After laser vitrectomy,95.3%of patients with vitreous opacity showed significant improvement in symptoms,and 90.3%expressed satisfac-tion with the improvement in postoperative visual quality.Patients'gender,age,preoperative vitreous opacity morphology,and refractive error below-6.00D had an impact on the treatment outcome(P<0.05).Python decision tree analysis demonstrated superior efficacy in patients aged>30-45 years with 6-12 months of symptom duration and refractive error<-6.00D.Stata18.0 OLS linear regression analysis showed that all examined variables were positively correlated at the 1%significance level,with patients'expected feelings having the greatest impact on postoperative satisfaction with treatment(r=1.053).Conclusion Ultra Q Nd:YAG laser vitreous ablation demonstrates high safety and patient satisfaction for vitreous opacity treatment.

Objective:To explore the effect of immobility on the quality of life in older adults.Methods:This cross-sectional study included 244 consecutive elderly patients aged 60 years and older who were admitted to the Department of Geriatrics at Xuanwu Hospital of Capital Medical University from May 2022 to March 2023.Among the participants, 52.5%(128/244)were male and 47.5%(116/244)were female, with a mean age of 69.2±7.4 years.All participants underwent a series of assessments, including the Short Physical Performance Battery(SPPB), grip strength measurement, gait speed evaluation, and the Timed Up and Go test(TUG).The Barthel Index was employed to assess activities of daily living, while the Medical Outcomes Study 36-Item Short Form Health Survey(SF-36)was used to evaluate quality of life.A score of SPPB ≤ 9 was used to diagnose immobility.Results:A total of 60 older adults met the criteria for immobility.Compared to the non-immobility group, the quality-of-life scores for older adults in the immobility group were significantly lower across various dimensions, including physical functioning, role-physical, bodily pain, general health, vitality, social functioning, physical component summary, and the total SF-36 score(all P<0.05).Furthermore, a positive correlation was identified between the SPPB scores and the quality-of-life scores across the dimensions of physical functioning, bodily pain, general health, vitality, social functioning, mental health, reported health transition, physical component summary, and the total SF-36 score among patients in the immobility group(all P<0.05).Additionally, older adults in the immobility group exhibited lower grip strength, slower gait speed, and longer TUG times, as well as a higher incidence of emergencies and falls over the past year(all P<0.05). Conclusions:The poorer quality of life and physical function, along with higher rates of emergencies and falls among older adults with immobility, indicate the necessity of addressing the health consequences that immobility inflicts on this population.

Objective:To investigate the efficacy of oral folic acid intervention in lung cancer patients with radiation esophagitis (RE) caused by concurrent chemoradiotherapy.Methods:In this randomized, controlled, single-center clinical trial, a total of 82 patients with stage N 2-N 3 lung cancer including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to October 2023 were prospectively included. All enrolled patients were randomly divided into the experimental group (folic acid group) and control group according to 1 vs. 1 of simple random method, and patients in both groups were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes [≥2 cycles of chemotherapy were completed during the same period of radiotherapy (≥40 Gy / 20 F) or targeted drugs were given simultaneously]. The severity of RE was evaluated using the modified common terminology criteria for adverse events criteria of the National Cancer Institute in both groups weekly at the onset of radiation esophagitis symptoms and thereafter until 1 week after the end of radiotherapy. Conventional treatment of RE was delivered according to the grading criteria of the Radiation Therapy Oncology Group. Patients in the folic acid group were given with folic acid tablets 30 mg/d orally at the beginning of radiotherapy until the end of radiotherapy, while those in the control group did not receive any drug intervention. The onset time, severity and duration of RE, and changes in the severity of esophageal toxicity after conventional treatment were recorded and analyzed. Serum folate value, serum vitamin B 12 value and homocysteine value were measured before and after radiotherapy. For continuous quantitative variables, independent sample t-test or independent sample rank-sum test was used for comparison among different groups. For categorical data, Chi-square test or Fisher's exact probability method was used for comparison among different groups. Results:During the observation period, no grade 4 or above RE was reported between two groups. The incidence of grade 0, 1, 2 and 3 RE in the folic acid and control groups was 10% (4/40) and 5% (2/41), 70% (28/40) and 42% (17/41), 15% (6/40) and 51% (21/41), 5% (2/40) and 2% (1/41), respectively. The differences were not statistically significant between two groups ( P=0.456). However, the incidence of grade 0-1 RE in the folic acid group was significantly higher than that in the control group ( Z=2.72, P=0.006). The median time of RE in the folic acid group and control group was 12 d (range 7-52 d) and 15 d (range 11-56 d) after the start of radiotherapy, respectively, with no statistically significant difference ( χ2=-0.75, P=0.456). However, median duration of the individual's most severe RE was 12 d (range 4-36 d) and 21 d (range 7-38 d) in the folic acid group and control groups, respectively, and the differences were statistically significant ( χ2=2.10, P=0.039). In the folic acid group, the grades of swallowing with pain and dysphagia were significantly declined after folic acid intervention, especially at 2 weeks after the occurrence of RE ( P=0.001, P=0.002). The remission rate of RE after 1 week in the folic acid group was higher than that in the control group, and the difference was statistically significant ( χ2=7.36, P=0.012). Conclusion:Oral intake of folic acid during concurrent chemoradiotherapy for lung cancer cannot reduce the incidence of RE, but it may reduce its severity, shorten the duration of the most severe RE in individuals, and have a certain protective effect.

Objective:To analyze the changes and significance in clinical cardiac indicators of early cardiac myocardial dysfunction and cardiac substructure dose during conventional radiotherapy for N 2-N 3 non-small cell lung cancer (NSCLC) with mediastinal lymph node metastases. Methods:The data of 34 NSCLC patients with lymph node metastases in regions 4-8 admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to August 2023 were observed and analyzed. All patients were treated with volumetric modulated arc therapy with a prescribed dose of 60-70 Gy. Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at 6 time points: within 1 week before radiotherapy ( t0); when the cumulative radiotherapy dose reaches 20 Gy ( t20), 40 Gy ( t40), 60 Gy ( t60) during radiotherapy; within 1 week after radiotherapy ( tp); 1 month after radiotherapy( tp1). Left ventricular global longitudinal strain (LVGLS) and left atrial global longitudinal strain (LAGLS) were assessed at 4 time points: t0, t40, tp and tp1, respectively. The changes in cardiac indicators at different time points during radiotherapy and their correlation with substructure doses were analyzed using analysis of variance, linear regression analysis, and Pearson correlation. Results:The correlation between cardiac substructure dose and mean heart dose (MHD) in the study cohort in the descending order was as follows: left ventricle ( B=0.43, P<0.001), right ventricle ( B=0.37, P=0.002), left atrium ( B=0.16, P<0.001), and right atrium ( B=0.15, P=0.001). There were significant differences in the changes of LVGLS and LAGLS across different time points ( F=3.13, P=0.029; F=17.18, P<0.001). At 1 month after radiation, LAGLS was significantly decreased compared to pre-radiation levels ( P=0.009), whereas no significant difference was observed in LVGLS ( P=1.000). No significant differences were observed in the changes of cTnT and NT-proBNP across different time points (all P>0.05). Significant correlations were identified between cTnT and right ventricle mean dose at t40 ( r=0.38, P=0.025), as well as between NT-proBNP and right atrium mean dose at t60 and tp ( r=0.54, P=0.001; r=0.41, P=0.016). Conclusions:At present, there is no significant difference between the sensitive serum markers of myocardial injury and LVGLS in detecting early myocardial injury. LAGLS may hold substantial clinical value. There is uncertainty about radiation injury and repair of various cardiac substructures.

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with al-terations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,trans-mission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assess-ment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.