OBJECTIVE To explore the mechanism of the active ingredient compatibility（quercetin， quercitrin and kaempferol at a mass ratio of 2∶9∶3）of Dimocarpus longan Lour. leaves（abbreviated as CDL） on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats. METHODS SD rats were randomly divided into blank control group， model group， metformin hydrochloride group （100 mg/kg）， and CDL high-， medium- and low-dose groups （280， 140， 75 mg/kg）， with 10 rats in each group. Rats in the blank control group were fed with standard chow， while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling， rats in each administration group were given corresponding drug solution， and rats in the blank control group and model group were intragastrically administered with equal volume of pure water， once a day， for consecutive 4 weeks. Fasting blood glucose （FBG） was detected at fixed time every week. The curves of oral glucose tolerance test （OGTT） and intraperitoneal insulin tolerance test （IPITT） were plotted， and the area under curve （AUC） was calculated. The pancreatic islet function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]，blood lipid indexes [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group， the FBG， AUC of IPITT curve， AUC of OGTT curve， HOMA-IR， the levels of FINS， TC， TG and LDL-C， as well as the protein and mRNA expression of phosphatase and tensin homolog， forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group （ P ＜0.05）. ISI， the levels of HDL-C and hepatic glycogen content， along with the protein and mRNA expression of PI3K， insulin receptor substrate-1， Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased （ P ＜0.05）. In model group rats， the arrangement of hepatocytes was irregular， the overall structure of pancreatic lobules was disordered， and a large number of inflammatory cell infiltration was observed. Compared with the model group， most of the above quantitative indexes were significantly reversed in the CDL high-dose group （ P ＜0.05）， and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders， elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.

OBJECTIVE To explore the mechanism of the active ingredient compatibility（quercetin， quercitrin and kaempferol at a mass ratio of 2∶9∶3）of Dimocarpus longan Lour. leaves（abbreviated as CDL） on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats. METHODS SD rats were randomly divided into blank control group， model group， metformin hydrochloride group （100 mg/kg）， and CDL high-， medium- and low-dose groups （280， 140， 75 mg/kg）， with 10 rats in each group. Rats in the blank control group were fed with standard chow， while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling， rats in each administration group were given corresponding drug solution， and rats in the blank control group and model group were intragastrically administered with equal volume of pure water， once a day， for consecutive 4 weeks. Fasting blood glucose （FBG） was detected at fixed time every week. The curves of oral glucose tolerance test （OGTT） and intraperitoneal insulin tolerance test （IPITT） were plotted， and the area under curve （AUC） was calculated. The pancreatic islet function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]，blood lipid indexes [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group， the FBG， AUC of IPITT curve， AUC of OGTT curve， HOMA-IR， the levels of FINS， TC， TG and LDL-C， as well as the protein and mRNA expression of phosphatase and tensin homolog， forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group （ P ＜0.05）. ISI， the levels of HDL-C and hepatic glycogen content， along with the protein and mRNA expression of PI3K， insulin receptor substrate-1， Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased （ P ＜0.05）. In model group rats， the arrangement of hepatocytes was irregular， the overall structure of pancreatic lobules was disordered， and a large number of inflammatory cell infiltration was observed. Compared with the model group， most of the above quantitative indexes were significantly reversed in the CDL high-dose group （ P ＜0.05）， and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders， elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.

Objective: To analyze the time-related factors influencing daily blood donation attendance at fixed donation sites in Nanjing and the heterogeneity among sites, and to provide evidence for optimizing site layout and operational management. Methods: Based on daily attendance data from 17 fixed donation sites in Nanjing for the full year of 2025, matched with contemporaneous meteorological and air quality data, a two-stage negative binomial generalized linear mixed model (NB-GLMM) was constructed. In the second stage, site-level static characteristics (number of scenic spots, daily operating hours, number of shopping malls, public transport stops, hospitals, universities, and residential buildings) were additionally incorporated. Model comparison was performed using Akaike information criterion (AIC). Significance of random effects was tested by likelihood ratio test, and site-specific random effects were extracted using empirical Bayes estimation. Robustness of the results was verified through residual diagnostics and multiple sensitivity analyses. Results: The first-stage model showed that rainfall was associated with lower attendance (IRR=0.943, P<0.001); holidays were associated with higher attendance (IRR=1.162, P<0.001); Saturdays and Sundays showed higher attendance than Mondays, with the strongest association on Sundays (IRR=1.195, P<0.001). Temperature exhibited a non-linear relationship (linear term P=0.051, quadratic term P=0.036). The joint results of the linear and quadratic terms for temperature suggested a nonlinear relationship between attendance and temperature. After introducing static characteristics in the second stage, the number of scenic spots (IRR=1.372, P=0.008) and daily operating hours (IRR=1.823, P<0.001) were found to be positively associated with attendance, while the numbers of shopping malls, public transport stops, hospitals, universities, and residential buildings showed no significant effects. Conclusion: Daily blood donation attendance at fixed sites in Nanjing is influenced by multiple factors including weather, day of the week, holidays, and site surroundings. Substantial heterogeneity exists among different sites; extended operating hours and more nearby scenic spots are associated with increased attendance.

ObjectiveTo compare the Children's Hepatic tumors International Collaboration （CHIC） and the new Chinese Children's Cancer Group （CCCG） hepatoblastoma （HB） risk stratification systems in terms of their prognostic prediction efficacy and chemotherapy guidance value for Chinese children with HB， aiming to identify the risk stratification system more suitable for Chinese HB patients. MethodsThis retrospective study analyzed the clinical data of 403 pediatric patients with HB aged ＜ 18 years who were initially diagnosed at The First Affiliated Hospital of Sun Yat-sen University between February 2010 and September 2023. The prognostic predictive efficacy and chemotherapy-guided value of the CHIC and CCCG risk stratification systems was compared. Statistical analysis was performed using SPSS 27.0. Results①Using the new CCCG risk stratification， the 5-year event-free survival （EFS） rates for children who received versus did not receive risk-stratified chemotherapy according to the CCCG-HB-2016 protocol were 82.5% and 67.7% （P=0.002）， respectively， and the 5-year overall survival （OS） rates were 91.5% and 85.1% （P=0.038）. Using CHIC risk stratification， the corresponding 5-year EFS rates for children who received versus did not receive risk-stratified chemotherapy according to the CCCG-HB-2016 protocol were 80.3% and 68.5% （P=0.030）， and the 5-year OS rates were 90.9% and 85.8% （P=0.151）. ②Among children treated with the CCCG-HB-2016 protocol stratified by the new CCCG system， the 5-year EFS rates for the very low-risk （6 cases）， low-risk （20 cases）， intermediate-risk （61 cases）， and high-risk （69 cases） groups were 100%， 94.1%， 94.7%， and 66.2% （P＜0.001）， respectively， and the 5-year OS rates were 100%， 100%， 96.5%， and 82.0% （P=0.017）. Among children treated with the CCCG-HB-2016 protocol stratified by the CHIC system， the 5-year EFS rates for the very low-risk （32 cases）， low-risk （22 cases）， intermediate-risk （37 cases）， and high-risk （54 cases） groups were 93.8%， 95.2%， 76.1%， and 66.8% （P=0.003）， respectively， and the 5-year OS rates were 93.1%， 100%， 89.5%， and 85.6% （P=0.190）. ③For patients receiving CCCG-HB-2016 risk-stratified chemotherapy， the P-values for EFS comparisons between the CHIC and new CCCG systems within the very low-risk， low-risk， intermediate-risk， and high-risk groups were 0.537， 0.879， 0.023， and 0.934， respectively. Among patients who received stratified chemotherapy according to the CCCG-HB-2016 regimen， the intermediate-risk group in the new CCCG risk stratification system exhibited a significant advantage in 5-year event-free survival （EFS） compared with the intermediate-risk group in the CHIC risk stratification system （94.7% vs. 76.1%）. ConclusionCompared to the CHIC risk stratification， the new CCCG stratification may offer better prognostic prediction and guidance value for chemotherapy in Chinese HB patients， with the intermediate-risk group showing superior outcomes.

POEMS syndrome is a rare condition associated with plasma cell disorders， and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease， the patients presented with lower limb weakness， hepatosplenomegaly， lymph node enlargement， ascites， hypothyroidism， positive M protein， and skin hyperpigmentation， and ¹⁸F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome， and the symptoms were relieved after immunomodulatory treatment.

Objective:To observe the effects of acupuncture on the motor function of Parkinson disease(PD)model mice and to investigate the neuroprotective effects of acupuncture on PD from the perspective of cellular senescence.Methods:C57BL/6J mice were randomly divided into a normal control(NC)group,a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)group,an acupuncture(ACU)group,and a rasagiline(RAS)group,with 6 mice in each group.Except for the mice in the NC group,all mice were injected intraperitoneally with MPTP[30 mg/(kg·bw)]to establish a PD mouse model.After the models were successfully established,mice in the ACU group received acupuncture at Baihui(GV20)and bilateral Yanglingquan(GB34)for 15 min,once a day for 14 consecutive days.Mice in the RAS group were treated with gavage of rasagiline mesylate[0.5 mg/(kg·bw)],once daily for 14 d.Mouse balance and motor functions were detected using the mouse fatigue rotating rod apparatus.Immunohistochemistry staining was used to detect the number of tyrosine hydroxylase(TH)-positive neurons and the protein expression levels of special AT-rich sequence-binding protein 1(SATB1),p21,and p53 in the substantia nigra(SN)region of the mouse brain in each group.The glutathione peroxidase(GSH-Px)activity of mouse brain SN tissue was detected by enzyme-linked immunosorbent assay.The protein expression levels of interleukin(IL)-6 and senescence-associated β-galactosidase(SA-β-gal)in the SN tissue of mice in each group were detected by Western blotting.The relative expression of SATB1,p21,and p53 mRNA in the SN of each group was detected by real-time quantitative polymerase chain reaction.Results:Compared to the NC group,the overall rod performance(ORP)score,the number of TH-positive neurons,and GSH-Px activity in the SN region were significantly lower in the mice in the MPTP group(P<0.01);compared to the MPTP group,the ORP score,the number of TH-positive neurons,and GSH-Px activity were significantly increased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly increased(P<0.01);compared to the MPTP group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly decreased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the relative expression of SATB1 protein and mRNA in the SN of mice in the MPTP group was significantly decreased(P<0.01);compared to mice in the MPTP group,mice in the ACU group and the RAS group showed significant increases in the relative expression of SATB1 protein and mRNA(P<0.01 or P<0.05).Conclusion:Acupuncture can improve motor function and increase the number of TH-positive neurons in the SN of PD model mice.Its neuroprotective effect may relate to the regulation of the SATB1/p21 signaling pathway and the inhibition of cellular senescence-related biomarker expression in the SN.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Objective:To explore the effects and safety of Qigong Pills in IVF-ET outcome of PCOS infertility patients with phlegm-dampness type.Methods:A randomized controlled trial study was carried out. In the Reproductive and Genetic Medicine Center of Dalian Women and Children Medical Center (Group) from January 2021 to December 2023, 60 patients with sputum and damp-induced PCOS infertility assisted by in-vitro fertilization and embryo transfer (IVF-ET) were enrolled and randomly divided into 2 groups by block randomization method, with 30 cases in each group. Patients in both groups took ethinylestradiol cyproterone tablets orally on the 2nd to 5th day of the 1st menstrual cycle before IVF-ET cycle, and received down-regulation treatment on the 18th to 20th day of menstruation. After confirming that the down-regulation standard was reached, Qigong Pills was added to the treatment group, and placebo was taken orally until the trigger day. Two groups of patients underwent transvaginal ultrasound-guided ovarian aspiration after injection of chorionic gonadotropin (hCG) for 24-36 h. The total amount of Gn, the days of Gn, the endometrial thickness of HCG, the number of eggs obtained, the rate of diprokaryotic (2PN) fertilization, the number of transferable embryos, the number of high-quality embryos, the rate of high-quality embryos, the incidence of OHSS and the clinical pregnancy rate were compared between the two groups.Results:Among the 60 patients, 28 cases in the final treatment group and 27 cases in the control group were included in the outcome index evaluation. During controlled hyperstimulation (COH), the total Gn [2 025 (1 575, 2 325) U vs. 2 700 (2 025, 3 150) U, Z=-3.67] and the number of Gn days of the treatment group [10 (8,11) d vs. 11 (9,13) d, Z=-2.31] were lower than those in control group ( P<0.001 or P<0.05). There was no statistical significance in endometrial thickness between 2 groups on HCG day ( P>0.05); the number of high-quality embryos [3 (3, 4) vs. 2 (2, 3), Z=0.11] and the rate of high-quality embryos [46.28% (87/188) vs. 35.19% (57/162), Z=4.42] in the treatment group were higher than those in the control group ( P<0.05). There was no statistical significance in the number of eggs obtained, the fertilization rate of 2PN and the number of transferable embryos between the two groups ( P>0.05). The incidence of OHSS was 3.6% (1/28) in the treatment group and 11.1% (3/27) in the control group, without statistical significance ( P=0.352). The clinical pregnancy rate was 53.6% (15/28) in the treatment group and 37.0% (10/27) in the control group, without statistical significance ( P=0.218). There was no significant difference in the safety indexes of liver and kidney function between 2 groups ( P>0.05). Conclusion:Qigong Pills combined with IVF-ET can effectively reduce the total amount of Gn and the number of days of treatment in PCOS infertility patients with phlegm-dampness type, increase the number and rate of high-quality embryos, and improve the outcome of IVF-ET, and it is safe and effective.

Objective Depression,a most common psychiatric disease,is defined in Traditional Chinese Medicine(TCM)as Yu Syndrome,i.e.,depression disorder,or Baihe Disease,i.e.,lily bulb disease,a category of emotional disorders treated with lily-based TCM preparations.In TCM,depression is managed through syndrome differentiation and treatment,which is characterized by high efficacy and safety.However,there is no unified standard for the classification of depression syndromes,which leads to a disconnection between the analysis of patients'medication patterns and their actual syndromes and hinders the study of medication patterns specific to particular syndromes.Therefore,this study is focused on investigating the medication patterns of different sub-types of depression patients based on an objective classification system of depression.Methods We searched for and retrieved clinical literature on TCM formulas for depression from relevant databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP Database,Sinomed,Web of Science,and PubMed.Information on patient symptoms and medication was standardized.Then,the symptoms and the medication frequency of depression patients were statistically analyzed.We used the K-means clustering method combined with implicit structural analysis to objectively categorize depression patients into sub-types.In addition,the main symptoms and core TCM formulas of each sub-type of depression patients were identified.On the basis of objective classification system,we also statistically analyzed the characteristics of herbs used on depression patients,including the 4 basic properties,the 5 flavors,the attributes,the therapeutic efficacy,and the co-occurrence patterns,which may help reveal the medication patterns.Results A total of 3 537 publications and 4 434 prescriptions were included in the analysis.By using the K-means algorithm and latent structure analysis methods,patients with depression were categorized into 9 sub-types,with Cluster 6 accounting for the largest proportion.The most common symptoms among depression patients were insomnia and a depressed mood.Medication frequency analysis showed that Radix Bupleuri(Chai Hu),Radix Paeoniae Alba(Bai Shao),Poria(Fu Ling),Rhizoma Chuanxiong(Chuan Xiong),and Radix Curcumae(Yu Jin)were the most commonly used TCM herbs.For the depression sub-types of Clusters 1,2,and 6,blood-activating and stasis-dissolving herbs were used most often.The depression sub-types of Clusters 3,4,5,8,and 9 were mainly treated with qi-regulating herbs,while the depression sub-type of Cluster 7 was treated with qi-supplementing herbs.Depression patients were mostly treated with herbs that were cold or warm in nature and had sweet,bitter,and pungent flavors.Moreover,treatments for Cluster 1 and Cluster 6 mainly targeted the spleen meridian,while those for Cluster 2,Cluster 3,Cluster 4 and Cluster 5 mainly targeted the heart meridian.The treatments for the other sub-types mainly targeted the liver meridian.The core TCM formulas for the 9 depression sub-types included Zishui Qinggan Decoction,Danzhi Xiaoyao Powder,Huanglian Wendan Tang,Chaihu Guizhi Tang,Modified Xiaoyao Powder,Qinggan Jieyu Tang,Xiaoyao Powder,Xuefu Zhuyu Decoction,and Bazhen Decoction.The most commonly used Chinese herbal medicinal formulas were Gan Cao-Chai Hu,Bai Shao-Chai Hu,and Chen Pi-Chai Hu.Conclusion Based on machine learning,this study reveals the scientific aspects of TCM typing and syndrome-based treatment.It clarifies the rationale for targeting different symptoms in depression treatment and provides theoretical support for clinicians to make medication prescriptions.It also presents a new perspective for investigating TCM medication patterns.

Objective:To compare the effects of standard cognitive behavioral therapy for insomnia (CBT-I) and enhanced cognitive behavioral therapy for insomnia(CBT-I Plus) in patients with chronic insomnia disorder comorbid anxiety or depressive symptoms.Methods:This prospective study included 148 patients with chronic insomnia disorder and anxiety/depression symptoms who were treated at the Sleep Disorder clinic of Shanghai Mental Health Center between July 2020 and August 2023. Participants (56 males, 92 females; aged 18-65 years, mean age 35.08±10.30 years) were randomly assigned in a 1∶2 ratio to the CBT-I group ( n=54) or CBT-I Plus group ( n=94). The CBT-I Plus group received additional treatments targeting anxiety and depressive symptoms. Treatment lasted 8 weeks, with assessment conducted at baseline, weeks 2, 4, and 8. Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAMD 17), anxiety severity with the Hamilton Anxiety Scale (HAMA), and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Paired sample t-tests were used to evaluate within-group changes, repeated-measures ANOVA compared treatment effects between groups, and ANCOVA was employed to adjust for confounding variables. Results:Significant reductions in PSQI, HAMD 17, and HAMA scores were observed in both groups after treatment: CBT-I group: PSQI ((14.15±2.54) vs. (7.50±3.35), t=13.25), HAMD 17 ((14.70±4.09) vs. (7.40±4.61), t=9.33), and HAMA ((14.94±4.11) vs. (5.56±3.67), t=12.38) (all P<0.001).CBT-I Plus group: PSQI ((14.87±3.01) vs. (7.19±3.86), t=18.75), HAMD 17 ((16.84±3.91) vs. (6.84±4.79), t=17.42), and HAMA ((15.57±3.93) vs. (6.10±4.57), t=18.39) (all P<0.001). After adjusting for HAMD 17 scores and medication use, no statistically significant between-group differences were observed in changes in PSQI, HAMD 17, and HAMA scores ( P>0.05). A significant time-by-group interaction was found for the PSQI daytime dysfunction subscale ( F=4.87, P<0.01). Conclusion:Both CBT-I and CBT-I Plus improve sleep and emotional symptoms in patients with chronic insomnia disorder and comorbid anxiety/depression symptoms. However, CBT-I Plus has no significant advantages over standard CBT-I. Further studies are needed to refine the timing and content of interventions.