Objective To explore the characteristics and correlation between perivascular spaces (PVS) and diffusion tensor image analysis along perivascular spaces (DTI-ALPS) index in patients with amnestic mild cognitive impairment (aMCI). Methods A retrospective study was conducted on a total of 118 participants, including cognitive normal (CN) healthy controls and aMCI patients, recruited from the Department of Neurology, Zhongshan Hospital, Fudan University from September 2020 to September 2022. All participants underwent structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). An automatic segmentation algorithm was used to quantify PVS metrics in the brain, and DTI-ALPS index was calculated based on DTI. Differences in DTI-ALPS index and PVS metrics between the CN and aMCI groups were compared. Multivariate logistic regression was used to identify independent factors influencing aMCI. Correlation analysis was performed to assess relationships among DTI-ALPS index, PVS metrics, and cognitive scores. Results A total of 80 CN healthy controls and 38 aMCI patients were included. The DTI-ALPS index was significantly lower in the aMCI group compared with the CN group (1.28±0.18 vs 1.37±0.21, P＝0.018), while differences in PVS metrics between groups were not statistically significant. Multivariate logistic regression analysis indicated that DTI-ALPS index was an independent factor affecting aMCI (OR＝0.097, 95%CI 0.011–0.833, P＝0.033). Correlation analysis revealed a positive relationship between DTI-ALPS index and MMSE score (r＝0.210, P＝0.023) as well as PVS length in the centrum semiovale (r＝0.216, P＝0.019). Conclusions The DTI-ALPS index may serve as an imaging biomarker for identifying early cognitive impairment, and patients with aMCI exhibit abnormal DTI-ALPS indices, suggesting that brain glymphatic system dysfunction may occur prior to morphological changes.

OBJECTIVE To investigate the absorption characteristics and tissue distribution of silybin （Sy） nanocrystals prepared by two methods in different intestinal segments of rats. METHODS Sy nanocrystals （i.e. Sy-NS-G and Sy-NS-F） with comparable particle sizes were prepared using high-pressure homogenization and anti-solvent precipitation methods， respectively. Rats were randomly divided into three groups： Sy raw drug group， Sy-NS-G group， and Sy-NS-F group. Each group was further divided into three subgroups with low， medium， and high （60， 120， 180 μg/mL） mass concentrations （calculated based on Sy）， with 3 rats in each subgroup. The absorption rate constant （Ka） and apparent absorption coefficient （Papp） of Sy raw drug， Sy-NS-G and Sy-NS-F in different intestinal segments were investigated by using the in vivo one-way intestinal perfusion experiment. Additionally， the rats were divided into three groups: Sy raw drug group， Sy-NS-G group， and Sy-NS-F group， with 20 rats in each group. Rats in each group were administered a single intragastric dose of 50 mg/kg （calculated based on Sy）. They were sacrificed at 0.3， 1， 4， 10， and 24 hours post-administration respectively， to investigate the tissue distribution of Sy raw drug， Sy- NS-G， and Sy-NS-F in the heart， liver， spleen， lungs， kidneys， brain and intestines. RESULTS In duodenum and jejunum， the Ka and Papp of the nanocrystals prepared by the two methods remained unchanged with the increase of Sy concentration， and there was no significant difference （P＞0.05）； the absorption of Sy-NS-F in the duodenum was greater than that of Sy-NS-G； the absorption sites of Sy-NS-G and Sy raw drug were mainly in the ileum， while those of Sy-NS-F were mainly in the duodenum and ileum. The concentrations of Sy-NS-G and Sy-NS-F in different tissues of rats were different； Sy-NS-G peaked in most tissues at 1 h， and the distribution concentration was as follows： intestine＞spleen＞heart＞lungs＞liver≈brain＞kidneys. Sy-NS-F reached its peak at 1 h， and the distribution concentration was in the order of intestine＞spleen＞kidney＞lung＞heart≈liver＞brain. CONCLUSIONS The absorption mode of Sy nanocrystals in the duodenum and ileum is mainly passive diffusion. In the duodenum， the absorption of Sy-NS-F is greater than that of Sy-NS-G； there are significant differences in the tissue distribution of Sy-NS-G and Sy-NS-F in rats.

Major depressive disorder with mixed features is a common, complex, and challenging-to-treat subtype of depression that poses significant difficulties for clinicians in practice. This review synthesizes the latest research, international guidelines, and expert consensus to provide clinical treatment references for managing patients with major depressive disorder with mixed features.

Objective:To describe the body mass index (BMI) level and long-term trends of Chinese older adults aged 65 and above.Methods:Older adults aged 65 and above from six waves (2002-2018) of the China Longitudinal Healthy Longevity Survey were selected as the study population. Multiple cross-sectional design with six survey waves conducted in 2002, 2005, 2008, 2011, 2014, and 2018 was adopted, enrolling 15 647, 15 358, 15 622, 9 166, 6 302, and 12 417 participants, respectively. Additionally, a total of 13, 755 participants were included in the cohort study design. Relevant information was collected through questionnaires and physical examinations. The χ2 trend test was used to compare the changes in the rates of underweight and overweight/obesity over the years, and the linear mixed-e?ects model (LMM) was used to fit trajectory curves of BMI changes with advancing age in older adults. Results:The baseline ages of the participants included in 2002, 2005, 2008, 2011, 2014, and 2018 were (85.16±11.26), (84.23±11.83), (84.99±12.16), (81.10±11.86), (78.89±11.30), and (83.08±12.42) years, respectively, with a relatively high proportion of females and rural residents. In the cohort study, the 13 755 participants had a median ( Q1, Q3) follow-up time of 6.5 (5.2, 10.0) years, with a cumulative follow-up duration of 109 041 person-years. In each wave, males had higher BMI than females, urban residents had higher BMI than rural residents, and BMI gradually decreased with increasing age (all P<0.001). The mean BMI of older adults in China increased from (19.37±3.80) kg/m2 in 2002 to (22.04±4.01) kg/m2 in 2018 ( P<0.001). Across all survey years, the prevalence of underweight was consistently higher in women than in men and in rural areas than in urban areas, with an upward trend as age increased (all P<0.001). In 2018, the underweight rates in the 65-79, 80-89, 90-99, and ≥100-year-old age groups were 8.0%, 16.7%, 26.2%, and 35.5%, respectively. Meanwhile, the prevalence of overweight/obesity was higher in men than in women and in urban areas than in rural areas, showing a declining trend with advancing age (all P<0.001). The prevalence of underweight among the older adults decreased significantly from 45.2% in 2002 to 18.9% in 2018 ( P<0.001), while the prevalence of overweight/obesity increased from 11.0% in 1998 to 29.6% in 2018 ( P<0.001). The trajectory curves fitted by the LMM model showed that individuals born in later decades had higher BMI levels at the same age compared to earlier cohorts. Conclusion:From 2002 to 2018, the BMI level among Chinese older adults showed an increasing trend. The prevalence of underweight showed a declining trend, while the rates of obesity and overweight increased. However, the underweight rate remained notably high among the oldest old.

Immune suppression in the tumor microenvironment (TME) is closely related to abnormal glycolysis. Tumor cells gain metabolic advantages and suppress immune responses through the "Warburg effect". Traditional Chinese medicine (TCM) has been shown to regulate key glycolysis enzymes (such as HK2 and PKM2), metabolic signaling pathways (such as PI3K/AKT/mTOR, HIF-1α) and non-coding RNAs at multiple targets, thus synergistically inhibiting lactate accumulation, improving vascular abnormalities, and relieving metabolic inhibition of immune cells. Studies have shown that TCM monomers and formulas can promote immune cell infiltration and functions, improve metabolic microenvironment, and with the assistance by the nano-delivery system, enhance the precision of treatment. However, the dynamic mechanism of the interaction between TCM-regulated glycolysis and TME has not been fully elucidated, for which single-cell sequencing and other technologies provide important technical support to facilitate in-depth analysis and clinical translational research. Future studies should be focused on the synergistic strategy of "metabolic reprogramming-immune activation" to provide new insights into the mechanisms of tumor immunotherapy.
Humans ; Tumor Microenvironment/immunology* ; Glycolysis/drug effects* ; Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology*

This article reports a diagnostically and therapeutically challenging case of small intestinal marginal zone lymphoma. The patient presented with recurrent abdominal pain as the chief complaint, and imaging revealed multifocal small bowel wall thickening with high uptake, multisegmental luminal stenosis, and proximal dilation. Initial diagnostic workup, including gastroscopy, colonoscopy, and enteroscopy with biopsy, failed to establish a definitive diagnosis. Empirical anti-tuberculosis therapy was ineffective. A repeat enteroscopic biopsy performed over eight months after symptom onset eventually confirmed the diagnosis of mucosa-associated lymphoid tissue (MALT) extranodal marginal zone lymphoma. Despite three different chemotherapy regimens, the patient's intestinal obstruction symptoms persisted, with imaging still showing multifocal bowel wall thickening and hypermetabolic activity. A critical diagnostic dilemma arose regarding whether the PET/CT-positive lesions represented residual lymphoma or fibrotic scarring, whether further chemotherapy adjustments were warranted, and whether surgical resection was necessary. Multidisciplinary discussion concluded that imaging had limited discriminatory value in this scenario and that surgical intervention should be pursued if feasible. The patient successfully underwent partial small bowel resection, with postoperative pathology confirming no residual lymphoma but significant fibrotic changes. The patient has since resumed a normal diet, with body weight nearly restored to pre-illness levels. This case highlights that fibrotic transformation is a common sequela of treated marginal zone lymphoma and that PET/CT may misleadingly suggest residual disease, potentially leading to unnecessary chemotherapy. Timely surgical intervention is crucial in such scenarios.

Major depressive disorder with mixed features is a common, complex, and challenging-to-treat subtype of depression that poses significant difficulties for clinicians in practice. This review synthesizes the latest research, international guidelines, and expert consensus to provide clinical treatment references for managing patients with major depressive disorder with mixed features.

Objective:To describe the body mass index (BMI) level and long-term trends of Chinese older adults aged 65 and above.Methods:Older adults aged 65 and above from six waves (2002-2018) of the China Longitudinal Healthy Longevity Survey were selected as the study population. Multiple cross-sectional design with six survey waves conducted in 2002, 2005, 2008, 2011, 2014, and 2018 was adopted, enrolling 15 647, 15 358, 15 622, 9 166, 6 302, and 12 417 participants, respectively. Additionally, a total of 13, 755 participants were included in the cohort study design. Relevant information was collected through questionnaires and physical examinations. The χ2 trend test was used to compare the changes in the rates of underweight and overweight/obesity over the years, and the linear mixed-e?ects model (LMM) was used to fit trajectory curves of BMI changes with advancing age in older adults. Results:The baseline ages of the participants included in 2002, 2005, 2008, 2011, 2014, and 2018 were (85.16±11.26), (84.23±11.83), (84.99±12.16), (81.10±11.86), (78.89±11.30), and (83.08±12.42) years, respectively, with a relatively high proportion of females and rural residents. In the cohort study, the 13 755 participants had a median ( Q1, Q3) follow-up time of 6.5 (5.2, 10.0) years, with a cumulative follow-up duration of 109 041 person-years. In each wave, males had higher BMI than females, urban residents had higher BMI than rural residents, and BMI gradually decreased with increasing age (all P<0.001). The mean BMI of older adults in China increased from (19.37±3.80) kg/m2 in 2002 to (22.04±4.01) kg/m2 in 2018 ( P<0.001). Across all survey years, the prevalence of underweight was consistently higher in women than in men and in rural areas than in urban areas, with an upward trend as age increased (all P<0.001). In 2018, the underweight rates in the 65-79, 80-89, 90-99, and ≥100-year-old age groups were 8.0%, 16.7%, 26.2%, and 35.5%, respectively. Meanwhile, the prevalence of overweight/obesity was higher in men than in women and in urban areas than in rural areas, showing a declining trend with advancing age (all P<0.001). The prevalence of underweight among the older adults decreased significantly from 45.2% in 2002 to 18.9% in 2018 ( P<0.001), while the prevalence of overweight/obesity increased from 11.0% in 1998 to 29.6% in 2018 ( P<0.001). The trajectory curves fitted by the LMM model showed that individuals born in later decades had higher BMI levels at the same age compared to earlier cohorts. Conclusion:From 2002 to 2018, the BMI level among Chinese older adults showed an increasing trend. The prevalence of underweight showed a declining trend, while the rates of obesity and overweight increased. However, the underweight rate remained notably high among the oldest old.

With population aging worldwide,Alzheimer's disease(AD)has become a serious human health issue.Owing in part to the complexity of the pathogenesis of AD,effective therapeutic options are lacking.Mesenchymal stem cell-derived exosomes(MSC-Exos)have powerful regenerative properties and repair functions,providing a new direction for treatment.They are donor-derived,easily stored,natural carriers,with low immunogenicity and a low risk of tumor formation.They have shown great potential in the treatment of AD and post-treatment rehabilitation.This article introduces the pathological mechanisms of AD and characteristics of MSC-Exos,provides a detailed review of the roles of MSC-Exos in the treatment of AD,including anti-inflammatory effects,immunomodulatory effects,and related signaling pathway modulation,and summarizes recent research progress,with the aim of providing a basis for the development of novel therapeutic approaches to AD.

With population aging worldwide,Alzheimer's disease(AD)has become a serious human health issue.Owing in part to the complexity of the pathogenesis of AD,effective therapeutic options are lacking.Mesenchymal stem cell-derived exosomes(MSC-Exos)have powerful regenerative properties and repair functions,providing a new direction for treatment.They are donor-derived,easily stored,natural carriers,with low immunogenicity and a low risk of tumor formation.They have shown great potential in the treatment of AD and post-treatment rehabilitation.This article introduces the pathological mechanisms of AD and characteristics of MSC-Exos,provides a detailed review of the roles of MSC-Exos in the treatment of AD,including anti-inflammatory effects,immunomodulatory effects,and related signaling pathway modulation,and summarizes recent research progress,with the aim of providing a basis for the development of novel therapeutic approaches to AD.