To report two cases of psychiatric symptoms associated with zonisamide, an antiepileptic drug, and raise clinical awareness of this potential adverse effect. Two male patients with epilepsy treated with zonisamide were retrospectively analyzed. Case 1 (25 years old) developed acute emotional and behavioral abnormalities (e.g., insomnia, aggression, incoherent speech) after switching from sodium valproate to zonisamide (200 mg/day). Case 2 (48 years old) had long-term zonisamide use (≥5 years) with persistent treatment-resistant psychotic symptoms (e.g., delusions, command hallucinations). Clinical courses, medication adjustments, and symptom responses were documented. In Case 1, psychiatric symptoms resolved after discontinuing zonisamide and switching to sodium valproate, with improved mood stability and reduced impulsivity. In Case 2, despite escalating antipsychotic medications (risperidone, clozapine), psychotic symptoms persisted, likely due to ongoing zonisamide use. Both cases highlighted zonisamide’s potential to exacerbate or induce psychiatric manifestations, possibly via mechanisms involving sodium/calcium channel inhibition and neurotransmitter dysregulation (e.g., dopamine, serotonin). Zonisamide can cause or worsen psychiatric symptoms, particularly in vulnerable individuals. Clinicians should monitor for mental health changes during zonisamide treatment and consider drug discontinuation or substitution with alternative antiepileptics (e.g., sodium valproate) if psychiatric adverse effects emerge. Awareness of this association is crucial to avoid misdiagnosis and optimize epilepsy management.

ObjectiveTo compare the clinical features of patients with hepatitis B virus （HBV）-related early-onset liver cancer and those with late-onset liver cancer， to assess the severity of the disease， and to provide a theoretical basis for the early diagnosis and treatment of liver cancer. MethodsA retrospective analysis was performed for 695 patients who were diagnosed with HBV-related liver cancer for the first time in Guangzhou Eighth People’s Hospital， Guangzhou Medical University， from January 2019 to August 2023， among whom 93 had early-onset liver cancer （defined as an age of50 years for female patients and40 years for male patients） and 602 had late-onset liver cancer （defined as an age of ≥50 years for female patients and ≥40 years for male patients）. Related clinical data were collected， including demographic data， clinical symptoms at initial diagnosis， comorbidities， smoking history， drinking history， family history， routine blood test results， biochemical parameters of liver function， serum alpha-fetoprotein（AFP）， virological indicators， coagulation function， and imaging findings. The pan-inflammatory indices neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， and lymphocyte-to-monocyte ratio （LMR） were calculated， as well as FIB-4 index， aspartate aminotransferase-to-platelet ratio index （APRI）， S index， Model for End-Stage Liver Disease （MELD） score， Child-Turcotte-Pugh （CTP） score， albumin-bilirubin （AIBL） grade， and Barcelona Clinic Liver Cancer （BCLC） stage. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or Fisher’s exact test were used for comparison of categorical data between two groups. ResultsThere were significant differences between the two groups in the proportion of male patients and the incidence rates of diabetes， hypertension， and fatty liver disease （χ²=6.357， 15.230， 11.467， and 14.204， all P0.05）， and compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly higher proportion of patients progressing to liver cancer without underlying cirrhosis （χ²=24.657， P0.001） and a significantly higher proportion of patients with advanced BCLC stage （χ²=6.172， P=0.046）. For the overall population， the most common clinical symptoms included abdominal distension， abdominal pain， poor appetite， weakness， a reduction in body weight， edema of both lower limbs， jaundice， yellow urine， and nausea， and 55 patients （7.9%） had no obvious symptoms at the time of diagnosis and were found to have liver cancer by routine reexamination， physical examination suggesting an increase in AFP， or radiological examination indicating hepatic space-occupying lesion； compared with the late-onset liver cancer group， the patients in the early-onset liver cancer group were more likely to have the symptoms of abdominal distension， abdominal pain， and jaundice （all P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had a significantly larger tumor diameter （Z=2.845， P=0.034）， with higher prevalence rates of multiple tumors and intrahepatic， perihepatic， or distant metastasis （χ²=5.889 and 4.079， both P0.05）， and there were significant differences between the two groups in tumor location and size （χ²=3.948 and 11.317， both P0.05）. Compared with the late-onset liver cancer group， the early-onset liver cancer group had significantly lower FIB-4 index， proportion of patients with HBsAg ≤1 500 IU/mL， and levels of LMR and Cr （all P0.05）， as well as significantly higher positive rate of HBeAg and levels of log₁₀ HBV DNA， AFP， WBC， Hb， PLT， NLR， PLR， TBil， ALT， Alb， and TC （all P0.05）. ConclusionCompared with late-onset liver cancer， patients with early-onset liver cancer tend to develop liver cancer without liver cirrhosis and have multiple tumors， obvious clinical symptoms， and advanced BCLC stage， which indicates a poor prognosis.

OBJECTIVES: To explore the molecular mechanism by which miR-124 affects cognitive function of sleep-deprived rats. METHODS: Fifty-four adult male SD rats were randomized into 6 groups (n=9), including a normal control group, a sleep deprivation (SD) model group, and 4 intracerebral microinjection groups in which the rats were subjected to stereotactic injection of miR-124 agomir, miR-124 agomir NC, miR-124 antagomir, or miR-124 antagomir into the lateral ventricle 7 days before SD modeling. The cognitive functions of the rats were evaluated with Morris water maze test, and pathological changes in the hippocampus were observed using HE staining. The expression level of miR-124 in hippocampal tissues of the rats was detected with qRT-PCR, and the expression level of apoptosis-related proteins and signaling pathway proteins were determined using Western blotting. RESULTS: In Morris water maze test, the SD rat models treated with miR-124 agomir showed a significantly shorter escape latency and fewer platform crossings with increased percentage of time and swimming distance in the fourth quadrant as compared with those in SD model group, while the rats treated with miR-124 antagomir exhibited worsened performance in the test. In the SD rat models, treatment with miR-124 agomir obviously lessened pathological changes in the hippocampus, while treatment with miR-124 antagomir significantly worsened the pathological changes. Compared with those in SD model group, the miR-124 agomir-treated rats showed an increased hippocampal expression of miR-124 with upregulated protein expressions of PI3K, p-AKT/AKT, and Bcl-2 and downregulated expressions of Bax and caspase-3 proteins, while rats treated with miR-124 antagomir showed significantly decreased hippocampal expression of miR-124 with lowered expressions of PI3K, p-AKT/AKT and Bcl-2 proteins and increased Bax and caspase-3 protein expressions. CONCLUSIONS High expression of miR-124 alleviates SD-induced cognitive decline and neuronal apoptosis in rats by activating the PI3K/AKT signaling pathway.
Animals ; MicroRNAs/metabolism* ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Male ; Rats, Sprague-Dawley ; Hippocampus/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cognition ; Rats ; Sleep Deprivation/metabolism* ; Apoptosis ; Maze Learning

Due to its high sensitivity and non-destructive nature, Raman spectroscopy has become an essential analytical tool in biopharmaceutical analysis and drug development. Despite of the computational demands, data requirements, or ethical considerations, artificial intelligence (AI) and particularly deep learning algorithms has further advanced Raman spectroscopy by enhancing data processing, feature extraction, and model optimization, which not only improves the accuracy and efficiency of Raman spectroscopy detection, but also greatly expands its range of application. AI-guided Raman spectroscopy has numerous applications in biomedicine, including characterizing drug structures, analyzing drug forms, controlling drug quality, identifying components, and studying drug-biomolecule interactions. AI-guided Raman spectroscopy has also revolutionized biomedical research and clinical diagnostics, particularly in disease early diagnosis and treatment optimization. Therefore, AI methods are crucial to advancing Raman spectroscopy in biopharmaceutical research and clinical diagnostics, offering new perspectives and tools for disease treatment and pharmaceutical process control. In summary, integrating AI and Raman spectroscopy in biomedicine has significantly improved analytical capabilities, offering innovative approaches for research and clinical applications.

Objective To explore the effectiveness of an integrated laparoscopic simulation training course (best essential surgical technique training, BEST) in enhancing laparoscopic peritoneal suturing techniques in surgical residents.Methods As an integrated two-stage program, the BEST course applied basic laparoscopic training system with simple molds in phase Ⅰ training, and then adopted advanced laparoscopic training system, 3D Laparoscope and ex-vivo animal models in phase Ⅱ training. The laparoscopic suturing techniques were practiced in phase Ⅱ training. From August 2021 to July 2024, surgical residents in the second year of the national standardized training program were divided into pilot and control groups based on whether they had undergone the BEST course. Two cases of laparoscopic peritoneal suture were performed by the surgical residents under supervision in the department of gastrointestinal surgery. The operative time, quality of suture, and independent completion rate were compared between the two groups.Results A total of 33 surgical residents (19 in pilot group and 14 in control group) were included in this study, and a total of 66 cases of laparoscopic peritoneal suture were performed (38 in pilot group and 28 in control group). The operative time was significantly shorter in pilot group than that in control group (15.7 min vs. 17.5 min, P=0.025). The quality of suture was significantly better in pilot group compared to control group (P=0.023). In pilot group, all peritoneal sutures were performed by residents independently, whereas in control group, 3 cases (10.7%) were assisted by the supervisor, and the independent completion rate was different significantly (P=0.039).Conclusions The BEST course can help improve surgical residents′ laparoscopic peritoneal suturing techniques and could be promoted in the national standardized training program for surgical residents.

Objective:To assess the association between possible sarcopenia and the risk for frailty in middle-aged and elderly adults in China.Methods:A prospective cohort study design was used in this study. Data were from the China Health and Retirement Longitudinal Study during 2011-2018 and the baseline data in 2011, the follow up was conducted in 2013, 2015 and 2018, respectively. Frailty index was used to evaluate frailty status, and grip strength and repetitive sitting-up time were measured to detect possible sarcopenia. Cox proportional hazards regression model was used to estimate the association between possible sarcopenia and the risk for frailty in middle-aged and older adults.Results:In a 44 884 person-years follow-up, a total of 586 cases with frailty were recorded, and the incidence density of frailty was 13.06 per 1 000 person-year. The risk for frailty was also higher in those who were aged 60 years and above ( HR=2.05, 95% CI: 1.71-2.45), had a primary school education level or below ( HR=1.55, 95% CI: 1.29-1.85), had waist-to-height ratio ≥0.5 ( HR=1.39, 95% CI: 1.11-1.75) and had depression ( HR=1.52, 95% CI: 1.28-1.81). Drinking was associated with reduced risk for frailty ( HR=0.76, 95% CI: 0.62-0.94). The risk for frailty increased ( HR=1.73, 95% CI: 1.47-2.05) in those who might has possible sarcopenia. Conclusions:In middle-aged and elderly adults, those with possible sarcopenia, lower education level, central obesity and depression might be at high risk for frailty, and early interventions for high-risk population can be taken to slow the progression of frailty.

Objective:To compare and observe the fundus imaging characteristics of eyes with glucocorticoid-related central serous chorioretinopathy (CSC).Methods:A retrospective clinical study. A total of 149 CSC patients with 166 eyes diagnosed at Department of Ophthalmology of The First Affiliated Hospital of Zhengzhou University from March 2021 to October 2024 were included in the study. The duration of the disease from the appearance of symptoms to treatment was less than 3 months. All affected eyes underwent best-corrected visual acuity (BCVA), fundus color photography, swept-source optical coherence tomography (SS-OCT), and fundus fluorescein angiography (FFA) examinations. BCVA was tested using an international standard vision chart and converted into logarithm of the minimum angle of resolution (logMAR) visual acuity for statistical analysis. The SS-OCT instrument measured subfoveal choroidal thickness (SFCT), central macular thickness (CMT), choroidal vascular volume (CVV), and the width and height of flat irregular pigment epithelial detachment (FIPED). FIPED, subretinal fibrin, and choroidal layer strong reflective spots were identified from SS-OCTA B-scan images; multiple leakages (leak points >3) were identified from FFA images. Based on the presence or absence of a clear history of glucocorticoid administration before the onset, patients were divided into glucocorticoid-related and non-glucocorticoid-related groups, comprising 41 patients with 53 eyes and 108 patients with 113 eyes, respectively. Clinical and fundus imaging characteristics of the two groups were compared. The comparison of quantitative data between the two groups was performed using independent samples t test or non-parametric independent samples Wilcoxon test; the comparison of qualitative data was performed using χ2 test. Results:Compared with the non-glucocorticoid-related group, the glucocorticoid-related group had a smaller male-to-female ratio and a higher bilateral incidence, and the differences were statistically significant ( χ2=4.925, 17.849; P<0.05). The logMAR BCVA for the glucocorticoid-related and non-glucocorticoid-related groups were 0.45±0.33 and 0.21±0.21, respectively; SFCT were (644.43±131.91) and (507.26±121.79) μm; CMT were (389.51±233.45) and (362.59±140.85) μm; CVV were (4.44±1.07) and (3.67±0.82) mm 3; FIPED incidence were 58.49% (31/58) and 20.35% (23/113), respectively; FIPED width and height were (1 122.01±533.98) and (742.90±388.79) μm, and (99.13±92.17) and (33.01±15.99) μm; subretinal fibrin were observed in 24 (45.28%, 24/53) and 15 (13.27%, 15/113) eyes; choroidal strong reflections were found in 38 (71.70%, 38/53) and 45 (39.82%, 45/113) eyes; multiple leak points were identified in 35 (66.03%, 35/53) and 40 (35.40%, 40/113) eyes, respectively. Compared with the non-glucocorticoid-related group, the glucocorticoid-related group had worse BCVA ( Z=-4.984), thicker SFCT ( t=6.586), larger CVV ( t=5.160), higher incidence of FIPED ( χ2=23.908), and greater width and height of FIPED ( t=2.895, Z=-3.703). The glucocorticoid-related group also had a significantly increased incidence of subretinal fibrin, choroidal strong reflections, and multiple leak points, with all differences being statistically significant ( χ2=20.565, 14.663, 13.675; P<0.05); however, the comparison of CMT showed no statistically significant difference ( Z=-0.651, P>0.05). Conclusion:Compared with non-glucocorticoid-related CSC, glucocorticoid-related CSC patients have poorer vision, are more likely to affect both eyes, show no gender bias; choroidal vascular dilation is more significant, and damage to the outer retina and retinal pigment epithelium is more severe.

Objective:To compare the clinical and imaging characteristics of eyes with idiopathic focal choroidal excavation (FCE) and acquired FCE, and to preliminarily analyze the association of FCE with different fundus diseases.Methods:A retrospective clinical study. A total of 90 patients (93 eyes) diagnosed with FCE at the Ophthalmology Department of The First Affiliated Hospital of Zhengzhou University from March 2021 to May 2024 were included in the study. All affected eyes underwent best-corrected visual acuity (BCVA) testing, intraocular pressure (IOP) measurement, ophthalmoscope, fundus color photography, and swept-source optical coherence tomography (SS-OCT). SS-OCT was used to measure subfoveal choroidal thickness (SFCT), choroidal thickness at the temporal, nasal, and inferior margins of the FCE, as well as the maximum width and depth of the FCE. Based on the presence of concomitant fundus diseases, FCE cases were divided into an idiopathic FCE group (51 eyes) and an acquired FCE group (42 eyes). Clinical characteristics at the initial and final visits were compared between the two groups. Clinical features were also analyzed for acquired FCE eyes with different associated fundus diseases. A logistic regression model was used to identify potential risk factors for FCE coexisting with other fundus diseases.Results:Compared to the idiopathic FCE group, the acquired FCE group had significantly decreased BCVA ( Z=?8.290), significantly increased FCE width ( Z=?2.762), and significantly higher incidence rates of saucer-shaped FCE ( χ2=8.352) and ellipsoid zone disruption ( χ2=7.999). These differences were all statistically significant ( P<0.05). No significant differences were found between the two groups in age, gender distribution, IOP, foveal involvement, proportion of conforming FCE, retinal pigment epithelium-Bruch’s membrane rupture, presence of hyperreflective material under the excavation, presence of surrounding thick vessels, FCE depth, SFCT, or choroidal thickness at the inferior, temporal, and nasal margins of the FCE ( P>0.05). Logistic regression analysis revealed that FCE width (odds ratio=1.002, 95% confidence interval: 1.001-1.004, P=0.005) was the sole risk factor for FCE coexisting with other fundus complications. In both the idiopathic and acquired FCE groups, FCE depth and width remained relatively stable during follow-up. BCVA improved in the acquired FCE group after treatment. Conclusions:FCE can coexist with various fundus diseases. FCE width is the only risk factor for the development of other fundus complications in FCE-affected eyes. Treating retinal or choroidal diseases associated with acquired FCE can provide visual benefits to patients.

Objective:To explore the association of central obesity, pain, their joint effect, and interaction with frailty in middle-aged and old people in China.Methods:A total of 14 359 participants aged ≥45 years in 2011, 2013 and 2015 were selected from the China Health and Retirement Longitudinal Study to construct a cohort database. Cox proportional hazards regression models were used to estimate the association of waist-to-height ratio (WHtR) and pain with the risk for frailty. Joint effect and interaction analyses were performed.Results:In the follow-up of 77 783 person-years, frailty developed in 3 198 participants, with an incidence density of 41.11 per 1 000 person-years. Compared with the Q1 level of WHtR, its Q2, Q3 and Q4 level increased risk for frailty by 17% ( HR=1.17, 95% CI: 1.05-1.31), 24% ( HR=1.24, 95% CI: 1.11-1.40), and 43% ( HR=1.43, 95% CI: 1.25-1.63), respectively. Compared with painlessness, suffering from pain increased the risk for frailty by 97% ( HR=1.97, 95% CI: 1.83-2.11), and having 1, 2, and ≥3 pain sites increased the risk by 42% ( HR=1.42, 95% CI: 1.25-1.61), 86% ( HR=1.86, 95% CI: 1.64-2.11), and 138% ( HR=2.38, 95% CI: 2.18-2.60), respectively. The results of restricted cubic spline showed that WHtR level was associated with the risk for frailty in a J-type dose-response relationship (total P<0.001, nonlinear P<0.001), and pain quantity was positively associated with the risk in a nonlinear dose-response relationship (total P<0.001, nonlinear P<0.001). Threshold effect analysis revealed that the inflection points of WHtR and pain site number were 0.46 and 2.00, respectively ( P<0.001). Joint effect analysis showed that the Q2, Q3 and Q4 levels of WHtR combined with pain increased the risk for frailty by 146% ( HR=2.46, 95% CI: 2.11-2.87), 169% ( HR=2.69, 95% CI: 2.30-3.16), and 157% ( HR=2.57, 95% CI: 2.18-3.03). Conclusions:The risk for frailty increased with the level of WHtR and the number of pain sites in middle-aged and old people, and there was joint effect between WHtR and pain. Comprehensive management and intervention of obesity and pain are significant for the early prevention of frailty.

Objective:To assess the association between possible sarcopenia and the risk for frailty in middle-aged and elderly adults in China.Methods:A prospective cohort study design was used in this study. Data were from the China Health and Retirement Longitudinal Study during 2011-2018 and the baseline data in 2011, the follow up was conducted in 2013, 2015 and 2018, respectively. Frailty index was used to evaluate frailty status, and grip strength and repetitive sitting-up time were measured to detect possible sarcopenia. Cox proportional hazards regression model was used to estimate the association between possible sarcopenia and the risk for frailty in middle-aged and older adults.Results:In a 44 884 person-years follow-up, a total of 586 cases with frailty were recorded, and the incidence density of frailty was 13.06 per 1 000 person-year. The risk for frailty was also higher in those who were aged 60 years and above ( HR=2.05, 95% CI: 1.71-2.45), had a primary school education level or below ( HR=1.55, 95% CI: 1.29-1.85), had waist-to-height ratio ≥0.5 ( HR=1.39, 95% CI: 1.11-1.75) and had depression ( HR=1.52, 95% CI: 1.28-1.81). Drinking was associated with reduced risk for frailty ( HR=0.76, 95% CI: 0.62-0.94). The risk for frailty increased ( HR=1.73, 95% CI: 1.47-2.05) in those who might has possible sarcopenia. Conclusions:In middle-aged and elderly adults, those with possible sarcopenia, lower education level, central obesity and depression might be at high risk for frailty, and early interventions for high-risk population can be taken to slow the progression of frailty.