ObjectiveTo investigate the mechanisms by which Shangxia Liangji pills improve cognitive function in Alzheimer's disease （AD） mice based on the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway， aiming to provide experimental evidence for its clinical use in AD treatment. MethodsFifty APP/PS1 double-transgenic mice were randomly divided into a model group， Shangxia Liangji pills low-dose group， medium-dose group， high-dose group， and donepezil hydrochloride group， with 10 mice in each group. Additionally， 10 C57BL/6 mice of the same genetic background were assigned to the normal group. Cognitive function was assessed using the Morris water maze and novel object recognition tests. Hippocampal pathological changes were observed using transmission electron microscopy and Nissl staining. Neuroinflammation in hippocampal tissue was detected by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of PI3K/Akt pathway-related proteins， postsynaptic density protein 95 （PSD95）， and amyloid precursor protein （APP） in hippocampal tissue were measured by Western blot. ResultsCompared with the normal group， the model group exhibited significantly increased total swimming distance and escape latency， significantly reduced number of platform crossings （P<0.01）， and a decreased recognition index （P<0.01）. Marked neuronal apoptosis was observed in the hippocampal region， with a marked reduction in the number of neurons in the CA3 region （P<0.01）. Levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in hippocampal tissue were significantly elevated （P<0.01）. APP expression in hippocampal tissue was markedly upregulated （P<0.01）， while PSD95， p-PI3K/PI3K， and p-Akt/Akt protein expression were significantly downregulated （P<0.01）. Compared with the model group， the Shangxia Liangji pills high-dose group showed significantly reduced total swimming distance and escape latency， significantly increased number of platform crossings （P<0.01）， and an elevated recognition index （P<0.01）. Hippocampal neuronal apoptosis was alleviated， with a significant increase in the number of neurons in the CA3 region （P<0.01）. Levels of IL-6， IL-1β， and TNF-α were significantly decreased （P<0.01）. APP expression was downregulated （P<0.05）， while PSD95， p-PI3K/PI3K， and p-Akt/Akt protein expression were significantly upregulated （P<0.01）. ConclusionShangxia Liangji pills may improve cognitive function in AD mice by modulating the PI3K/Akt pathway， thereby reducing neuroinflammation and alleviating neuronal and synaptic injury.

The morphological changes and functions of mitochondria are closely associated with the development and progression of non-alcoholic fatty liver disease （NAFLD）. Dynamin-related protein 1 （Drp1） is one of the primary proteins determining mitochondrial fission， and its activity is strictly controlled to ensure the balance of mitochondrial dynamics according to cellular needs. Drp1 can enhance mitochondrial interactions and mitochondrial fission by promoting the formation of endoplasmic reticulum tubules， and the phosphorylation state and deacetylation of Drp1 can also affect the morphological changes of mitochondria， thereby affecting the status of NAFLD. This article elaborates on the role and mechanism of action of Drp1 in the progression of NAFLD， in order to provide ideas for targeted therapy for NAFLD.

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Objective To investigate the expression levels of peroxisome proliferator-activated receptor gamma coactivator-1β(PGC-1β),hypoxia-inducible factor-1α(HIF-1α),and resistin(RETN)in gouty arthri-tis(GA),and analyze their correlation with the degree of joint damage.Methods A total of 134 patients with GA in the hospital from January 2022 to October 2023 were selected as GA group,and 134 healthy people who underwent the physical examination in the same period were selected as control group.The serum expression levels of PGC-1β,HIF-1α and Retn were compared between the two groups.The expression levels of PGC-1β,HIF-1α and Retn in serum and synovial fluid of patients with different clinical characteristics in GA group were compared,the degree of joint destruction was graded according to the subjective pain grading method(VAS)and the patients were divided into a severe GA subgroup of 78 cases and a mild GA subgroup of 56 ca-ses.The expression levels of PGC-1β,HIF-1α,RETN,bone destruction factors[β-cross linked degradation products(β-CTX),tartrate resistant acid phosphatase-5b(TRACP5b),receptor activator of nuclear factor kappa B ligand(RANKL)]and inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)]were compared among different degrees of joint destruction,and the correlation between serum and syno-vial fluid PGC-1β,HIF-1α,RETN and the degree of joint destruction,bone destruction factors,and inflamma-tory factors was analyzed.Results The expression level of PGC-1β in serum of GA group was lower than that of the control group,while the expression levels of HIF-1α and RETN in serum were higher than those of the control group(P＜0.05).There were statistically significant differences in serum and synovial fluid PGC-1β,HIF-1α,and RETN levels among GA patients with different clinical stages,affected joints,disease duration,and annual seizure frequency(P＜0.05).The expression levels of PGC-1β in the serum and synovial fluid of the severe GA subgroup were lower than those of the mild GA subgroup(P＜0.05),while the expression lev-els of HIF-1α and RETN were higher than those of the mild GA subgroup(P＜0.05).The expression levels ofβ-CTX and TRACP5b in the severe GA subgroup were higher than those in the mild GA subgroup(P＜0.05),while the expression level of RANKL was lower than that in the mild GA subgroup(P＜0.05).PGC-1βin serum and synovial fluid was negatively correlated with the degree of joint destruction,β-CTX,TRACP5b,TNF-α,and IL-1β,and positively correlated with RANKL.HIF-1α and RETN were positively correlated with the degree of joint destruction,β-CTX,TRACP5b,TNF-α,and IL-1β,and negatively correlated with RANKL.Conclusion PGC-1β,HIF-1α,and RETN are abnormally expressed in patients with GA,and are closely associ-ated with the degree of joint destruction,bone destruction factors,and inflammatory factors.They are expec-ted to become reliable indicators for evaluating the occurrence and progression of GA.

Objective To investigate the efficacy of modified use of Huanglian Jiedu Decoction plus Xijiao Dihuang Decoction in the treatment of patients with psoriasis vulgaris of blood-heat syndrome and to observe its effect on Th1/Th2 balance in the patients.Methods The investigation was carried out in a total of 130 patients with psoriasis vulgaris of blood-heat syndrome,who were admitted to the dermatology department of the First Affiliated Hospital of Henan University of Chinese Medicine between January 2022 and June 2023.The patients were randomly divided into an observation group and a control group by the random number table method,with 65 patients in each group.The control group was treated with conventional western medicine,while the observation group was treated with modification of Huanglian Jiedu Decoction plus Xijiao Dihuang Decoction on the basis of treatment for the control group.Both groups were treated for four consecutive weeks and were followed up for one year.The changes in the scores of Psoriasis Area and Severity Index(PASI)and Dermatology Life Quality Index(DLQI),levels of peripheral blood Th1/Th2 balance indicators,and levels of peripheral Th1/Th2-related factors such as γ-interferon(INF-γ),interleukin 2(IL-2),and interleukin 4(IL-4)in the two groups of patients before and after treatment were observed.Moreover,the clinical efficacy and adverse reactions during treatment were evaluated,and the recurrent cases within one year in the two groups were counted.Results(1)After four weeks of treatment,the total effective rate of the observation group was 90.77%(59/65),and that of the control group was 76.92%(50/65).The intergroup comparison showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P<0.05).(2)After treatment,the scores of PASI and DLQI in the two groups of patients were decreased when compared with those before treatment(P<0.05),and the decrease of PASI and DLQI scores in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the serum levels of Th1/Th2-related factors such as INF-γ and IL-2 in the two groups of patients were decreased when compared with those before treatment(P<0.05),and IL-4 level was increased when compared with that before treatment(P<0.05),and the decrease of serum INF-γ and IL-2 levels and the increase of serum IL-4 level in the observation group were significantly superior to those in the control group(P<0.05 or P<0.01).(4)After treatment,the peripheral blood levels of Th1/Th2 balance indicators of Th1,Th2 and Th1/Th2 in the two groups of patients were decreased when compared with those before treatment(P<0.05),and the decrease of peripheral blood Th1,Th2 and Th1/Th2 levels in the observation group was significantly superior to that in the control group(P<0.01).(5)The recurrence rate of the observation group was 20.69%(12/58)and that of the control group was 38.33%(23/60),and the recurrence time in the observation group was(8.49±1.43)months and that of the control group was(5.36±0.95)months.The intergroup comparison showed that the one-year recurrence rate of the observation group was significantly decreased compared with that of the control group(P<0.05),and the recurrence time was significantly prolonged compared with that of the control group(P<0.05).(6)The medicine-induced adverse reaction rate in the observation group was 10.77%(7/65)and that in the control group was 12.31%(8/65),and the intergroup comparison showed that the difference was not statistically significant(P>0.05).Conclusion Modified use of Huanglian Jiedu Decoction plus Xijiao Dihuang Decoction is effective on enhancing the clinical efficacy of patients with psoriasis vulgaris of blood-heat syndrome,and on improving the balance of Th1/Th2 and the severity of the disease,delaying the recurrence of psoriasis vulgaris,and reducing the recurrence rate,with high safety.

Objective To understand the equity and influencing factors of maternal health service utilization in Changning District, Shanghai. Methods A convenience sampling method was used to conduct a questionnaire survey among mothers of children aged 1 to 1.5 years old who received health services from the child health care clinics and EPI clinics of 10 community health service centers in Changning District, Shanghai from March to April 2022. Count data was expressed by frequency and percentage. Chi-square analysis, binomial logistic regression analysis, and multivariate logistic regression analysis were used to analyze fairness-related factors. Rate difference, rate ratio and concentration index were used to represent fairness. Results A total of 696 subjects were investigated, with an average age of (33.35±4.76) years. There were statistically significant differences in service utilization among women with different household registrations only in early pregnancy registration (χ²=11.026, P=0.001) and postpartum visits (χ²=4.989, P=0.026). Women with a career showed differently in folic acid supplement (χ²=6.247, P=0.012), early pregnancy registration (χ²=12.989, P=0.002), physical examination in 42 days postpartum (χ²=4.446, P=0.035) and postpartum contraception (χ²=4.061, P=0.044), and the differences were statistically significant. Women with different monthly family income had a statistically significant difference in pre-pregnancy examination (χ²=8.977, P=0.030) and postpartum visit (χ²=16.114, P=0.001). There was a statistically significant difference between women with maternity insurance or not in the early pregnancy registration (χ²=10.576, P=0.001) and physical examination in 42 days postpartum (χ²=8.166, P=0.004). The results of the multivariate analysis showed that occupation (OR=2.616, 95% CI: 1.142-5.990) and maternity insurance (OR=4.490, 95% CI: 1.992~10.120) affected the utilization of service in early pregnancy registration. The monthly household income (OR=0.278, 95% CI: 0.124-0.625) affected the utilization of services in postpartum visit. At the same time, the monthly household income (10,000-19,999: OR=0.286, 95% CI: 0.090-0.907; ≥30,000: OR=0.180, 95% CI: 0.041-0.801) also affected the utilization of service in physical examination in 42 days postpartum. Conclusion The equity of maternal health care service utilization overall is good in central area in Shanghai, but there is still room for improvement. It is necessary to strengthen community mobilization, propagandize maternal health services, and expand the coverage of maternity insurance to improve the equity of maternal health service utilization and provide equal access to maternity health services.

OBJECTIVE: To observe the clinical efficacy of warming acupuncture combined with western medication for oligoasthenoteratozoospermia of kidney-yang insufficiency and its effects on the levels of interleukin (IL)-6 and IL-10 in seminal plasma. METHODS: A total of 60 patients with oligoasthenoteratozoospermia of kidney-yang insufficiency were randomly divided into a combination group and a medication group, with 30 cases in each group. The medication group was treated with levocarnitine oral solution orally, 10 mL once, 3 times a day. On the basis of the treatment in the medication group, warming acupuncture was applied at Baihui (GV20), Guanyuan (CV4) and Mingmen (GV4) in the combination group, once every other day, 3 times a week. Both groups were treated for 12 weeks. Before and after treatment, the TCM syndrome score was observed, the semen routine indexes (the sperm concentration, progressive [PR] sperm motility, PR + non-progressive [NP] sperm motility and sperm malformation rate), the serum sex hormones indexes (follicle-stimulating hormone [FSH], luteinizing hormone [LH], testosterone [T] and estradiol [E₂]), as well as the IL-6 and IL-10 levels in seminal plasma were detected, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, except for the hyposexuality score in the medication group, the each item scores and total scores of TCM syndrome were decreased compared with those before treatment (P<0.01, P<0.05), the sperm malformation rates, serum FSH and LH levels, IL-6 levels in the seminal plasma were decreased compared with those before treatment (P<0.01, P<0.05), the PR sperm motility, PR + NP sperm motility, serum T levels, IL-10 levels in the seminal plasma were increased compared with those before treatment (P<0.01, P<0.05) in the two groups; the sperm concentration was increased compared with that before treatment in the combination group (P<0.01). After treatment, compared with the medication group, except for the hyposexuality and frequent nocturia scores, the each item scores and total score of TCM syndrome were lower (P<0.01, P<0.05); the sperm concentration, PR sperm motility and PR + NP sperm motility, serum T level, IL-10 level in the seminal plasma were higher (P<0.01, P<0.05); sperm malformation rate, serum FSH and LH levels, IL-6 level in the seminal plasma were lower (P<0.01, P<0.05) in the combination group. The total effective rate was 83.8% (25/30) in the combination group, which was superior to 60.0% (18/30) in the medication group (P<0.05). CONCLUSION Warming acupuncture combined with western medication can effectively treat oligoasthenoteratozoospermia of kidney-yang insufficiency, regulate the levels of sex hormones, and its mechanism may be related to the down-regulation of IL-6 level and the up-regulation of IL-10 level in seminal plasma.
Humans ; Male ; Interleukin-10/genetics* ; Interleukin-6/genetics* ; Adult ; Semen/metabolism* ; Acupuncture Therapy ; Oligospermia/drug therapy* ; Yang Deficiency/physiopathology* ; Kidney/physiopathology* ; Young Adult ; Asthenozoospermia/drug therapy* ; Combined Modality Therapy ; Treatment Outcome

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Objective:To compare the dose-response effects of single-fraction ultra-high dose rate (FLASH) and conventional dose rate (CONV) whole abdominal irradiation (WAI) with X-rays on acute radiation-induced intestinal injury in mice, in order to identify optimal dose parameters and potential mechanisms.Methods:A total of 186 male C57BL/6J mice were randomly assigned to a non-irradiation group ( n=6), FLASH irradiation groups ( n=90), and CONV irradiation groups ( n=90). Acute radiation-induced intestinal injury models were established using single-fraction WAI with 11, 12, 13, 14, and 15 Gy X-rays (200 Gy/s for FLASH and 4 Gy/min for CONV). Changes in body weight, stool characteristics, and disease activity index (DAI) scores were assessed at 9 d post-irradiation. At 7 d post-irradiation at 11, 12, and 13 Gy, the intestines were collected for macroscopic examination and length measurement. The small intestine was selected for HE staining and quantitative analysis of intestinal crypt number and mucosal epithelial thickness. The survival of mice was assessed at 15 d post-WAI across all dose groups. Results:After single-fraction WAI at 11, 12, and 13 Gy, the body weight was higher in the FLASH group than that in the CONV group ( t=10.17, 12.65, 10.16, P<0.05). The DAI scores for the FLASH group were 1.00±1.10, 3.17±0.75, and 2.83±1.17, respectively, which were lower than those of the CONV group (4.33±0.52, 7.00±0.00, 8.60±0.55; t=8.70, 11.71, 14.99, P<0.05). However, after WAI at 14 Gy and 15 Gy, there were no significant differences in body weight and DAI between the FLASH group and the CONV group ( P>0.05). At 7 d after single-fraction WAI at 11, 12, and 13 Gy, mice in the FLASH group exhibited less intestinal congestion, edema, and shortening compared with the CONV group. The difference between the FLASH and CONV groups were statistically significant in small intestine length at 11 and 13 Gy ( t=4.42, 3.78, P<0.05), and in colorectal length at 11 and 12 Gy ( t=3.97, 3.12, P<0.05). Small intestine HE staining revealed superior preservation of intestinal architecture in the FLASH group compared with the CONV group, characterized by longer villi, increased crypt numbers, thicker mucosal epithelium, and enhanced structural integrity. The differences in crypt number and mucosal epithelial thickness were statistically significant ( tcrypt=13.10, 23.80, 11.90; tmucosal=5.75, 2.64, 7.74; P<0.05). At 15 d post-irradiation, the survival rate in the 15 Gy FLASH group was higher than that in the CONV group (50% vs. 10%, χ2=5.39, P<0.05), with a median survival extension of 6 d ( HR=0.340, 95% CI: 0.115 4-0.999 9). No significant survival differences were observed between the FLASH group and the CONV group at 11, 12, 13, and 14 Gy ( P>0.05). Conclusions:FLASH irradiation significantly alleviated acute radiation-induced intestinal injury from medium single-fraction WAI with 11, 12, and 13 Gy X-rays compared with CONV irradiation, and showed potential to improve mouse survival after single-fraction WAI at 15 Gy. This effect is likely associated with the preservation of intestinal crypts and exhibits a dose-dependent relationship.