Uveal melanoma(UM)is a rare but highly aggressive intraocular malignancy. Although it accounts for less than 5% of all melanoma cases, UM is the most common primary intraocular malignancy in adults. In recent years, advances in molecular targeted therapies and immunomodulatory strategies have provided new opportunities for the clinical management of UM. This review summarizes the pathogenesis, molecular biomarkers, and major therapeutic advances in UM, with particular emphasis on analyzing the research achievements and clinical application prospects of signaling pathway-targeted inhibitors, immune checkpoint inhibitors, and combination treatment strategies. The potential value of individualized treatment and the limitations of current therapeutic approaches are also discussed. Current evidence suggest that multidisciplinary intervention and precision molecular diagnosis and treatment may significantly improve the prognosis of patients with UM, providing references for future clinical research and the optimization of therapeutic strategies.

Objective:To investigate the differences of the glymphatic system (GS) function between patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and healthy controls and between different seizure types by using diffusion tensor imaging along perivascular space (DTI-ALPS), and to analyze the correlation between GS function and the course of disease, as well as the efficacy of predicting the surgical outcome.Methods:This study was a cross-sectional study. A total of 171 patients with mTLE-HS (mTLE-HS group) and 75 healthy volunteers (HC group) were retrospectively enrolled from July 2009 to July 2021 at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University. The general information of all subjects, such as seizure type (partial seizure, secondary generalized seizure), surgical outcome, etc., was analyzed. The 3D magnetization prepared rapid gradient echo T 1WI and DTI sequence images were collected. The VBM analysis method was used to segment cerebrospinal fluid and calculate the volume. The ALPS index of the bilateral brain was calculated using the Atlas-based DTI-ALPS method. Independent sample t-test or paired t test were used to compare the ALPS index between the mTLE-HS group and HC group, and between patients with different seizure types. Pearson correlation analysis was used to analyze the correlation between bilateral ALPS index and disease duration in mTLE-HS group. The predictive value of the ALPS index for surgical outcomes was evaluated by receiver operating characteristics curve and area under the curve. Results:Among the 171 mTLE-HS patients, 98 patients were mTLE with left-side HS (mTLE-LHS) and 73 patients were mTLE with right-side HS (mTLE-RHS); 37 patients underwent surgical treatment, including 27 with good prognosis and 10 with poor prognosis. Compared with the HC group, the left-side ALPS index of mTLE-LHS and mTLE-RHS were both decreased ( P<0.05). The right-side ALPS index in mTLE-RHS was lower than that in the HC group ( P<0.001). There was no significant difference in the right-side ALPS index between mTLE-LHS and HC group ( P=0.080). The ALPS index on the affected side of patients with secondary generalized seizures was significantly lower than that of patients with only partial seizures (all P<0.05), but the difference in ALPS index on the healthy side was not statistically significant( P>0.05). The left-side and right-side ALPS index in mTLE-LHS were negatively correlated with disease duration ( r=-0.272, P=0.007; r=-0.307, P=0.002), but no significant correlation was found between the left-side or right-side ALPS index in mTLE-RHS (all P>0.05). The DTI-ALPS index on the affected side in mTLE-HS patients exhibited good diagnostic accuracy for surgical outcome classification, with an area under the curve of 0.778. Conclusions:The patients with mTLE-HS exhibit dysfunction of the GS, and the degree of impairment is related to the type of seizure and the course of epilepsy. The ALPS index, which characterizes the function of GS, demonstrates good diagnostic accuracy for classifying surgical outcomes.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Inter-estingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17 μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated pro-tein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Objective:To explore the changes of brain excitation/inhibition balance and gray matter volume (GMV) and their correlations with clinical features in benign childhood epilepsy with centrotemporal spikes (BECTS).Methods:A cross-sectional study was performed; 83 BECTS children enrolled from Department of Diagnostic Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2015 to January 2024 were selected as BECTS group. During the same period, 101 age- and gender-matched healthy children were recruited as healthy control group through advertisements in local primary schools. Data of conventional MRI and resting-state functional MRI (rs-fMRI) of the two groups were collected. Whole brain GMV was analyzed by voxel-based morphometry (VBM), and Hurst index was calculated based on time series data of blood oxygen level dependent (BOLD) signal of rs-fMRI. Correlations of GMV and Hurst index with disease duration and onset age in children with BECTS were explored by Pearson correlation analysis.Results:Compared with the healthy control group, the BECTS group had significantly increased GMV and decreased Hurst index in the bilateral Rolandic region ( P<0.05). Pearson correlation analysis showed that in the BECTS group, GMV in bilateral Rolandic region was negatively correlated with onset age ( r=-0.267, P=0.015) and positively correlated with disease course ( r=0.267, P=0.015); Hurst index in bilateral Rolandic region was positively correlated with onset age ( r=0.323, P=0.003) and negatively correlated with disease course ( r=-0.240, P=0.029); Hurst index was negatively correlated with GMV in bilateral Rolandic region ( r=-0.328, P=0.003). Conclusion:BECTS children have excitation/inhibition imbalance in epilepsy-related regions and cortical structural delay, and both of them are related to onset age and disease course.

The integrated medical and elderly care model provides comprehensive medical and elderly care services by establishing medical facilities in elderly care institutions or forming close cooperative relationships with surrounding medical institutions. Currently， there are 87，000 paired partnerships established nationwide between medical and health institutions and elderly care service institutions， and more than 7，800 integrated medical and elderly care institutions have obtained the qualifications of medical and health institutions and completed elderly care service registration. This model not only meets the elderly’s healthcare needs but also provides life care， psychological support， and social activities， thereby improving their quality of life. However， the integrated medical and elderly care model also faces numerous ethical dilemmas in practice. This paper aimed to explore in depth the ethical dilemmas and countermeasures optimization in the work of elderly care institutions under this model， to promote the improvement of service quality， comprehensively guarantee the rights and interests of the elderly， and promote the healthy development of this model in practice. Under this model， the elderly care institutions not only bear the responsibility of providing long-term care and life services but also need to cooperate with medical institutions to provide healthcare and health management services for the elderly. By exploring the practical paths for elderly care institutions to address the ethical dilemmas faced with this model， feasible solutions were proposed to enhance the welfare of the elderly and promote the harmonious development of society.

Hyperuricemia is a chronic metabolic disease resulting from purine metabolic dysfunction and is classified under the category of"blood turbidity"in traditional Chinese medicine.Our team termed it"acid turbidity,"and its pathogenesis is closely related to the dynamic evolution of the clear and the turbid components.With the change of modern people's diet structure,the incidence of hyperuricemia is increasing annually owing to the intake of fatty,sweet foods and alcohol.Therefore,this paper explores hyperuricemia from the"indigestion of spleen and stomach"theory.The core pathogenesis of hyperuricemia is indigestion of spleen and stomach,the inversion of clear and turbid substances,and endogenous acid turbidity.The initial manifestation of hyperuricemia is the internal retention of acid turbidity and ascending-descending disharmony;the gradual manifestation of this disease is that indigestion causes heat,and acid turbidity transforms into poison;the final manifestation of this disease is that secular indigestion causes deficiency and the inversion of clear and turbid substances.It can be summarized into three syndromes:syndromes of internal retention of dampness-turbidity,dampness-heat toxin amassment,and dampness-heat due to spleen deficiency.Therefore,this paper proposes to treat the disease according to different syndromes,with ascending the clear and descending the turbid as the core of treatment.And the therapeutic approach employs the flexible application of three methods:transportation,resolving,and transformation.For syndrome of internal retention of dampness-turbidity,treatment focuses on promoting spleen transportation to eliminate dampness;for syndrome of dampness-heat toxin amassment,the strategy is to resolve indigestion and purge heat;and for syndrome of dampness-heat due to spleen deficiency,the aim is to resolve turbidity and clear heat.By ascending the clear and descending the turbid,so that"returning the clear and the turbid to the original,"the spleen and stomach regain harmony,functions of ascending and descending are reestablished,and hyperuricemia can be effectively managed.

Hyperuricemia is a chronic metabolic disease resulting from purine metabolic dysfunction and is classified under the category of"blood turbidity"in traditional Chinese medicine.Our team termed it"acid turbidity,"and its pathogenesis is closely related to the dynamic evolution of the clear and the turbid components.With the change of modern people's diet structure,the incidence of hyperuricemia is increasing annually owing to the intake of fatty,sweet foods and alcohol.Therefore,this paper explores hyperuricemia from the"indigestion of spleen and stomach"theory.The core pathogenesis of hyperuricemia is indigestion of spleen and stomach,the inversion of clear and turbid substances,and endogenous acid turbidity.The initial manifestation of hyperuricemia is the internal retention of acid turbidity and ascending-descending disharmony;the gradual manifestation of this disease is that indigestion causes heat,and acid turbidity transforms into poison;the final manifestation of this disease is that secular indigestion causes deficiency and the inversion of clear and turbid substances.It can be summarized into three syndromes:syndromes of internal retention of dampness-turbidity,dampness-heat toxin amassment,and dampness-heat due to spleen deficiency.Therefore,this paper proposes to treat the disease according to different syndromes,with ascending the clear and descending the turbid as the core of treatment.And the therapeutic approach employs the flexible application of three methods:transportation,resolving,and transformation.For syndrome of internal retention of dampness-turbidity,treatment focuses on promoting spleen transportation to eliminate dampness;for syndrome of dampness-heat toxin amassment,the strategy is to resolve indigestion and purge heat;and for syndrome of dampness-heat due to spleen deficiency,the aim is to resolve turbidity and clear heat.By ascending the clear and descending the turbid,so that"returning the clear and the turbid to the original,"the spleen and stomach regain harmony,functions of ascending and descending are reestablished,and hyperuricemia can be effectively managed.

Objective:To explore the changes of brain excitation/inhibition balance and gray matter volume (GMV) and their correlations with clinical features in benign childhood epilepsy with centrotemporal spikes (BECTS).Methods:A cross-sectional study was performed; 83 BECTS children enrolled from Department of Diagnostic Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2015 to January 2024 were selected as BECTS group. During the same period, 101 age- and gender-matched healthy children were recruited as healthy control group through advertisements in local primary schools. Data of conventional MRI and resting-state functional MRI (rs-fMRI) of the two groups were collected. Whole brain GMV was analyzed by voxel-based morphometry (VBM), and Hurst index was calculated based on time series data of blood oxygen level dependent (BOLD) signal of rs-fMRI. Correlations of GMV and Hurst index with disease duration and onset age in children with BECTS were explored by Pearson correlation analysis.Results:Compared with the healthy control group, the BECTS group had significantly increased GMV and decreased Hurst index in the bilateral Rolandic region ( P<0.05). Pearson correlation analysis showed that in the BECTS group, GMV in bilateral Rolandic region was negatively correlated with onset age ( r=-0.267, P=0.015) and positively correlated with disease course ( r=0.267, P=0.015); Hurst index in bilateral Rolandic region was positively correlated with onset age ( r=0.323, P=0.003) and negatively correlated with disease course ( r=-0.240, P=0.029); Hurst index was negatively correlated with GMV in bilateral Rolandic region ( r=-0.328, P=0.003). Conclusion:BECTS children have excitation/inhibition imbalance in epilepsy-related regions and cortical structural delay, and both of them are related to onset age and disease course.

Objective:To investigate the differences of the glymphatic system (GS) function between patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and healthy controls and between different seizure types by using diffusion tensor imaging along perivascular space (DTI-ALPS), and to analyze the correlation between GS function and the course of disease, as well as the efficacy of predicting the surgical outcome.Methods:This study was a cross-sectional study. A total of 171 patients with mTLE-HS (mTLE-HS group) and 75 healthy volunteers (HC group) were retrospectively enrolled from July 2009 to July 2021 at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University. The general information of all subjects, such as seizure type (partial seizure, secondary generalized seizure), surgical outcome, etc., was analyzed. The 3D magnetization prepared rapid gradient echo T 1WI and DTI sequence images were collected. The VBM analysis method was used to segment cerebrospinal fluid and calculate the volume. The ALPS index of the bilateral brain was calculated using the Atlas-based DTI-ALPS method. Independent sample t-test or paired t test were used to compare the ALPS index between the mTLE-HS group and HC group, and between patients with different seizure types. Pearson correlation analysis was used to analyze the correlation between bilateral ALPS index and disease duration in mTLE-HS group. The predictive value of the ALPS index for surgical outcomes was evaluated by receiver operating characteristics curve and area under the curve. Results:Among the 171 mTLE-HS patients, 98 patients were mTLE with left-side HS (mTLE-LHS) and 73 patients were mTLE with right-side HS (mTLE-RHS); 37 patients underwent surgical treatment, including 27 with good prognosis and 10 with poor prognosis. Compared with the HC group, the left-side ALPS index of mTLE-LHS and mTLE-RHS were both decreased ( P<0.05). The right-side ALPS index in mTLE-RHS was lower than that in the HC group ( P<0.001). There was no significant difference in the right-side ALPS index between mTLE-LHS and HC group ( P=0.080). The ALPS index on the affected side of patients with secondary generalized seizures was significantly lower than that of patients with only partial seizures (all P<0.05), but the difference in ALPS index on the healthy side was not statistically significant( P>0.05). The left-side and right-side ALPS index in mTLE-LHS were negatively correlated with disease duration ( r=-0.272, P=0.007; r=-0.307, P=0.002), but no significant correlation was found between the left-side or right-side ALPS index in mTLE-RHS (all P>0.05). The DTI-ALPS index on the affected side in mTLE-HS patients exhibited good diagnostic accuracy for surgical outcome classification, with an area under the curve of 0.778. Conclusions:The patients with mTLE-HS exhibit dysfunction of the GS, and the degree of impairment is related to the type of seizure and the course of epilepsy. The ALPS index, which characterizes the function of GS, demonstrates good diagnostic accuracy for classifying surgical outcomes.