ObjectiveTo observe the effects of Dihuang Yinzi （DY） on motor dysfunction in rats with advanced Parkinson's disease （PD） and to investigate the mechanisms by which DY improves advanced PD symptoms through the "gut microbiota-short-chain fatty acids （SCFAs）-inflammation-neuroprotection pathway". MethodsAn advanced PD rat model was induced by rotenone. Rats were divided into a normal group， model group， positive drug group （levodopa， 50 mg·kg^-1）， and DY low-， medium-， and high-dose groups （5.2， 10.4， 20.8 g·kg^-1）. After 7 days of administration， motor function was evaluated using the open-field， pole-climbing， and inclined plate tests. Hematoxylin-eosin （HE） staining was used to observe pathological changes in the substantia nigra and colon， and immunohistochemistry was performed to detect α-Synuclein （α-Syn） and tyrosine hydroxylase （TH） expression in the substantia nigra. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of dopamine （DA）， 5-hydroxytryptamine （5-HT）， 3，4-dihydroxyphenylacetic acid （DOPAC）， Levodopa， homovanillic acid （HVA）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）. Western blot analysis was used to detect the expression of zonula occludens-1 （ZO-1） and occludin. Gut microbiota diversity was analyzed by 16S rRNA sequencing， and gas chromatography （GC） was used to determine the content of SCFAs in colonic contents. ResultsCompared with the normal group， the model group showed significantly decreased movement speed and distance in the open-field test， prolonged pole-climbing time， and reduced retention angle on the inclined plate （P<0.01）， accompanied by increased α-Syn expression （P<0.01） and decreased TH expression （P<0.01） in the brain. Compared with the model group， all DY dose groups improved motor dysfunction in advanced PD rats to varying degrees （P<0.05， P<0.01） and alleviated pathological damage in the brain and colon. High-dose DY significantly reduced α-Syn aggregation in the substantia nigra （P<0.01） and increased TH expression （P<0.01）. ELISA and Western blot results showed that， compared with the normal group， the model group exhibited decreased levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum （P<0.01）， increased levels of TNF-α， IL-6， and IL-1β in the colon and striatum （P<0.01）， and significantly reduced expression of ZO-1 （P<0.05） and occludin in the colon （P<0.01）. Compared with the model group， all DY dose groups increased the levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum to varying degrees （P<0.05， P<0.01）. In the high-dose DY group， the levels of TNF-α， IL-6， and IL-1β in the colon and striatum were reduced （P<0.01）， while the expression of ZO-1 （P<0.05） and occludin in the intestine was increased. The 16S rRNA sequencing results indicated that the relative abundances of Actinobacteriota， Enterobacteriaceae， and Erysipelotrichaceae were increased in the model group， whereas the relative abundances of Bacteroidota， class Clostridia， Lachnospiraceae， and Akkermansia muciniphila were decreased. These changes were effectively reversed after high-dose DY intervention. GC analysis showed that the content of SCFAs in the colonic contents of rats in the model group was decreased （P<0.05， P<0.01）， while after high-dose DY intervention， the levels of acetate， propionate， isobutyrate， and butyrate were significantly increased （P<0.05， P<0.01）. ConclusionDY may exert therapeutic effects in advanced PD by regulating the gut microbiota-SCFAs-inflammation pathway.

Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Objective To screen ferroptosis genes related to the prognosis of cervical cancer and to construct a prognosis model. Methods Ferroptosis genes were obtained from FerrDb database, and cervical cancer related data were obtained from The Genome-Wide Association Study Catalog database and The Cancer Genome Atlas database. Transcriptome-Wide Association Study, colocalization analysis and differential expression analysis were conducted to screen out candidate ferroptosis genes; Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted on candidate genes. Univariate Cox regression analysis was used to further screen out genes related to the prognosis of cervical cancer. Kaplan-Meier method was used to analyze the relationship between genes and the overall survival of patients. The expression levels of genes in pan-cancer were analyzed through the TIMER database. Two prognostic models were conducted, Model 1 included age and tumor stage, while Model 2 incorporated age, tumor stage, and prognostic genes. The predictive capabilities of the two models were compared. Results A total of 91 candidate genes related to ferroptosis were obtained. Univariate Cox regression analysis showed that 15 genes were associated with the prognosis of cervical cancer. CA9, SCD, TFRC, QSOX1 and CDO1 were risk factors affecting the prognosis of cervical cancer patients (P＜0.05), while PTPN6, ALOXE3, HELLS, IFNG, MIOX, ALOX12B, DUOX1, ALOX15, AQP3 and IDO1 were protective factors (P＜0.05). The mRNA expression levels of the 15 genes showed significant upregulation or downregulation in at least 7 types of cancers, among which TFRC was associated with the largest number of cancer types. Kaplan-Meier analysis showed that HELLS, DUOX1 and ALOXE3 were associated with poor prognosis in cervical cancer. The AUC of the model 1 for predicting 1-year and 3-year overall survival rates of cervical cancer patients was 0.455 and 0.478, and the AUC of Model 2 was 0.854 and 0.595. Model 2 (C-index = 0.727) had better predictive ability than Model 1 (C-index = 0.502). Conclusion The prognostic model composed of 15 prognostic-related genes selected based on bioinformatics has better predictive performance for the survival outcomes of cervical cancer patients, providing important reference value for the prognostic assessment of cervical cancer patients.

Lipid metabolism relates to tumor proliferation, progression, and immune escape. With the rapid development of immunotherapy, the relationship between immunotherapy and lipid metabolism has been constantly explored. On the one hand, immunotherapy can cause dyslipidemia and accelerate the progression of atherosclerosis, which has been neglected by clinicians. On the other hand, lipid metabolism can affect antitumor immunity at multiple levels and potentially influence the efficacy of immunotherapy. Lipid metabolism-regulating drugs also have the potential to synergize with immunotherapy. This review summarizes relevant research evidence to inspire further exploration.

Objective:To investigate the influencing factors of green procurement for medical equipment,so as to provide theoretical basis and policy insights for promoting practices of green procurement for medical institutions.Methods:Based on literature review and expert interviews,a questionnaire about influencing factors of green procurement for medical equipment was formulated,which was used to conduct questionnaire survey for medical institutions of secondary and tertiary grades in Shandong province.The questionnaire included the measured indicators and basic information of medical institutions from four dimensions:pressure of external system(7 items),leadership support(4 items),organizational inertia(5 items),and collaboration degree of stakeholder(5 items).The Likert 5-level scale was adopted to conduct scoring of questionnaire,and the differences in various influencing factors between secondary grade hospital and tertiary grade hospital were compared and analyzed.Results:The scores of tertiary grade hospital were respectively 4.00(3.14,4.82),4.25(4.00,5.00),and 3.60(3.00,4.00)at pressure of external system,leadership support(4 items),organizational inertia(5 items)of three dimensions,and they were 3.86(3.11,4.14),4.00(3.75,5.00),and 3.20(2.80,3.80)at secondary grade hospital,and the differences of them between secondary grade hospital and tertiary grade hospital were significant(Z=-2.243,-2.654,-2.538,P<0.05).There was not significant difference at the dimension of collaboration degree of stakeholder between secondary and tertiary hospitals(P>0.05).Conclusion:A series of measures,such as adopting policy support with differentiation,establishing multi-level incentive mechanisms,reducing organizational change resistance,and improving multi-party coordination mechanisms,can further promote green procurement of medical institutions.

Objective:To investigate the diagnostic value of contrast-enhanced ultrasound（CEUS）in solid pseudopapillary tumor of pancreas（SPTP），summarize the CEUS characteristics of SPTP，and to compare its CEUS enhancement with contrast-enhanced computed tomography（CECT）.Methods:In this retrospective study，baseline characteristics，basic ultrasound and CEUS images，CECT images of 70 patients diagnosed as SPTP from January 2009 to August 2023 were collected. Images were analyzed for extraction of key features and diagnostic accuracies of both CEUS and CECT were calculated. The relationships between ultrasound features and lesion size of SPTP were analyzed by Point-Biserial correlation analysis and Student t test. The diagnostic accuracy was compared by Mann-Whitney U test. Results:Iso-enhancement（55.7%，39/70）was commonly appeared in the early phase of CEUS for SPTP，while hypo-enhancement（74.3%，52/70）was the most common in the late phase. And the most common enhancement pattern was iso-hypo enhancement（41.4%，29/70）. Lesion membrane enhancement（47.1%，33/70），intralesional compartmentalization（28.6%，20/70），and intralesional vessels（25.7%，18/70）were the 3 typical signs found in CEUS for SPTP，which were correlated with lesion size（ P＜0.001）. Differences were found between the enhancement pattern of SPTP in CEUS and CECT，in which the most common enhancement patterns were hypo-hypo enhancement（41.4%，24/58）and iso-iso enhancement（29.3%，17/58）along with progressive enhancement. The diagnostic accuracies of CEUS and CECT were 71.4% and 74.1% respectively without statistically significant difference（ P=0.733）. Conclusions:CEUS shows high application value in the diagnosis of SPTP，and the accuracy of CEUS is comparable to that of CECT.

Objective:To quantitatively summarize the catechol-O-methyltransferase ( COMT) gene Val158Met polymorphism and the risk of obsessive-compulsive disorder (OCD). Methods:We searched databases including PubMed, Embase, Weipu and Wanfang for randomized controlled trials (RCTs) investigating the association between COMT gene polymorphisms and OCD up to November 1, 2023. Studies that reported genotype frequencies for both OCD patients and general healthy controls were included. Stata11 software was used to calculate pooled odds ratios ( OR) with 95% CI, perform heterogeneity test, and assess publication bias. Results:19 studies with 2, 393 OCD patients and 4, 134 healthy controls were included. The overall results showed that the Val158Met polymorphism was associated with OCD patients (allele model: OR=1.10, 95% CI: 1.02-1.20, P=0.016; homozygote model: OR=1.25, 95% CI:1.05-1.49, P=0.014; recessive model: OR=1.18, 95% CI:1.01-1.37, P=0.040). In the ethnic-stratified analysis, this significant association was mainly observed in Caucasians (allele model: OR=1.17, 95% CI:1.06-1.30, P=0.003; homozygote model: OR=1.35, 95% CI: 1.08-1.67, P=0.008; recessive model: OR=1.21, 95% CI: 1.01-1.44, P=0.041; dominant: OR=1.20, 95% CI: 1.01-1.43 P=0.040), but not in Asians. In gender-stratified analysis, Met-homozygote was associated with male OCD ( OR=1.75, 95% CI: 1.00-3.04, P=0.049). Moreover, the additional analysis found that the risk of OCD was significantly increased in Caucasian males (allele model: OR=1.48, 95% CI: 1.08-2.03, P=0.014; heterozygote model: OR=1.41, 95% CI: 1.03-1.93, P=0.030; dominant model: OR=1.60, 95% CI:1.08-2.38, P=0.020). Conclusion:This meta-analysis suggests that the COMT gene Val158Met polymorphism is associated with an increased risk of OCD in males, particularly in Caucasian males.

Objective To explore the efficiency of indocyanine green (ICG) fluorescence imaging-guided hepatectomy and its short-term prognosis in patients with primary liver carcinoma. Methods Retrospective analysis was conducted on 166 patients diagnosed with primary liver carcinoma and admitted to the Department of Hepatobiliary Surgery of Shanghai General Hospital affiliated to Shanghai Jiao Tong University School of Medicine from June 2018 to June 2021. Patients were categorized into ICG group (n=72) and non-ICG group (n=94) based on the utilization of ICG during surgery. Moreover, the clinical information of preoperation, intraoperation, and postoperation were collected and compared between the two groups. ICG fluorescence images of the lesions in the ICG group were recorded for analysis. Results ICG fluorescence intensity is associated with the histopathology, differentiation grade of primary liver cancer, and the presence of liver cirrhosis. Hepatocellular carcinoma lesions predominantly displayed partial fluorescence, while intrahepatic cholangiocarcinoma lesions showed circular fluorescence. Well differentiated tumors exhibited complete fluorescence (7/11), moderately differentiated tumors demonstrated partial fluorescence (28/51), and poorly differentiated tumors displayed circular fluorescence (7/10). Most patients with liver cirrhosis exhibited partial fluorescence (18/35) or complete fluorescence (13/35).Compared to the non-ICG group, the ICG group demonstrated higher serum albumin levels on the first (34.6 g/L vs. 31.4 g/L) and the third postoperative days (32.4 g/L vs. 31.2 g/L)(P<0.001). Conversely, the ICG group showed shorter operation time (170 min vs. 210 min), lower rate of intraoperative hepatic portal blockade (9.7% vs. 33.0%), less intraoperative blood loss (400 mL vs. 430 mL), shorter postoperative hospital stay (10 d vs. 14 d), and lower incidence of short-term postoperative complications (4.2% vs. 20.2%) (P<0.05) compared to the non-ICG group. Conclusions ICG fluorescence intensity is associated with the histopathology, differentiation grade of primary liver cancer, and the presence of liver cirrhosis.The judicious application of ICG fluorescence imaging technology alongside surgical techniques holds promise for improving short-term prognosis and expediting the postoperative recovery.

ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress （CRS） and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank， model， positive drug （diazepam， 1 mg·kg^-1）， and low-， medium-， and high-dose （0.75， 1.5， 3 g·kg^-1， respectively） Fufang Kangjiaolv capsules groups. After 14 days of administration， the elevated plus maze test， open field test， light and dark box test， and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats， and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of zonula occludens-1 （ZO-1） and occludin in the colon of rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the colon， serum， and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1， occludin， nuclear factor-κB p65 （NF-κB p65） in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. ResultsCompared with the blank group， the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze， the time and frequency of rats entering the central area of the open field， the time of entering the open box， the times of passing through the light and dark box， and the number of unburied beads （P<0.05， P<0.01）. Compared with the model group， Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees， and the high-dose group had the best effect， with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze （P<0.05）， the number of rats entering the central area in the open field （P<0.05）， the time of entering the open box， the times of passing through the light and dark boxes， and the number of unburied beads （P<0.01）. Moreover， the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes， Deferribacterota， Romboutsia， and Phascolarctobacterium， while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota， Bacteroides， norank f norank o Clostridia UCG-014， and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group， the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon （P<0.01）， elevated levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated protein level of NF-κB p65 in the colon and hippocampus （P<0.01）， and down-regulated protein level of BDNF in the hippocampus （P<0.05）. Compared with the model group， high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon （P<0.01）， lowered the levels of TNF-α， IL-6， and IL-β in the colon， serum， and hippocampus （P<0.01）， up-regulated the protein levels of ZO-1 （P<0.01） and occludin （P<0.05） in the colon， down-regulated the protein level of NF-κB p65 in the colon and hippocampus （P<0.05）， and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance， up-regulating the expression of tight junction proteins in the colon， repairing intestinal mucosal mechanical barrier， and down-regulating NF-κB/BDNF signaling pathway， thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis， providing a new idea for further research.