Luteolin is a natural flavonoid compound exists in various fruits and vegetables. Recent studies have indicated that luteolin has variety pharmacological effects, including a wide range of antidepressant properties. Here, we systematically review the preclinical studies and limited clinical evidence on the antidepressant and neuroprotective effects of luteolin to fully explore its antidepressant power. Network pharmacology and molecular docking analyses contribute to a better understanding of the preclinical models of depression and antidepressant properties of luteolin. Seventeen preclinical studies were included that combined network pharmacology and molecular docking analyses to clarify the antidepressant mechanism of luteolin and its antidepressant targets. The antidepressant effects of luteolin may involve promoting intracellular noradrenaline (NE) uptake; inhibiting 5-hydroxytryptamine (5-HT) reuptake; upregulating the expression of synaptophysin, postsynaptic density protein 95, brain-derived neurotrophic factor, B cell lymphoma protein-2, superoxide dismutase, and glutathione S-transferase; and decreasing the expression of malondialdehyde, caspase-3, and amyloid-beta peptides. The antidepressant effects of luteolin are mediated by various mechanisms, including anti-oxidative stress, anti-apoptosis, anti-inflammation, anti-endoplasmic reticulum stress, dopamine transport, synaptic protection, hypothalamic-pituitary-adrenal axis regulation, and 5-HT metabolism. Additionally, we identified insulin-like growth factor 1 receptor (IGF1R), AKT serine/threonine kinase 1 (AKT1), prostaglandin-endoperoxide synthase 2 (PTGS2), estrogen receptor alpha (ESR1), and epidermal growth factor receptor (EGFR) as potential targets, luteolin has an ideal affinity for these targets, suggesting that it may play a positive role in depression through multiple targets, mechanisms, and pathways. However, the clinical efficacy of luteolin and its potential direct targets must be confirmed in further multicenter clinical case-control and molecular targeting studies.

The study aims to investigate the impacts of prolyl oligopeptidase (POP) on the replication of foot-and-mouth disease virus (FMDV) in BHK-21 cells. Firstly, the effects of FMDV replication on POP expression in BHK-21 cells were analyzed by Western blotting and Real-time reverse transcription polymerase chain reaction (RT-qPCR). Secondly, a eukaryotic expression plasmid for POP was constructed, and the effects of POP overexpression on the replication of two different serotypes of FMDV were assessed by Western blotting, RT-qPCR, and virus titer assays. Thirdly, specific small interfering RNAs (siRNAs) targeting POP were synthesized, and their efficiency in interfering with endogenous POP expression was identified by RT-qPCR. The impacts of downregulating endogenous POP expression on FMDV replication were further evaluated by Western blotting, RT-qPCR, and virus titer assays. The results indicated that FMDV infection did not significantly affect POP expression in BHK-21 cells. Overexpression of POP dose-dependently enhanced the replication of both FMDV/O and FMDV/A serotypes. Conversely, siRNA-mediated downregulation of endogenous POP expression markedly suppressed FMDV/O replication. This study is the first to demonstrated that the role of the host POP protein in promoting FMDV replication in BHK-21 cells, thereby providing a critical theoretical foundation and potential molecular targets for developing efficient candidate cell strains for foot-and-mouth disease inactivated vaccines.
Foot-and-Mouth Disease Virus/genetics* ; Virus Replication/genetics* ; Prolyl Oligopeptidases ; Serine Endopeptidases/physiology* ; Animals ; Cell Line ; RNA, Small Interfering/genetics* ; Foot-and-Mouth Disease/virology* ; Cricetinae

Objective To compare the analgesic effects and adverse reactions between intercostal nerve block (ICNB) and patient controlled intravenous analgesia (PCIA). Methods From August 2022 to January 2023, 180 patients with lung cancer who underwent thoracoscopic surgery were randomly divided into two groups: ICNB group (n=90) and PCIA group (n=90). The postoperative pain degree (VAS), location, nature; adverse events, such as nausea, vomiting, and dizziness; and other clinical symptoms were analyzed. Results The most common site of postoperative pain in both groups was surgical incision, and the nature of pain was distending pain. At 12 and 24 h after the operation, the pain degree in the ICNB group (1.10±0.91, 3.12±1.29) was markedly lower than that in PCIA group (1.44±0.86, 4.32±1.30, P=0.010, P<0.001). The incidence of nausea, vomiting, and dizziness in the ICNB group (5.56%, 23.33%) was noticeably lower than that in the PCIA group (35.56%, 51.11%, P<0.001, P<0.001). Total hospitalization expense in the ICNB group (41 043.16±10 885.63 yuan) was significantly lower than that in PCIA group (45 283.99±11 036.36 yuan, P=0.010). Conclusion The analgesic effect of intercostal nerve block is better than that of patient-controlled intravenous analgesia pump in patients with lung cancer after minimally invasive surgery, and the incidence of adverse reactions is low.

Objective: To observe the effect of Xipayimaizibizi oral liquid (XP) in an overactive bladder (OAB) experimental rat model and to explore its pharmacological mechanisms. Methods: Network pharmacology was used to explore the potential mechanisms of action of XP. The rats underwent bladder outlet obstruction surgery and were administered the corresponding drug concentrations by gavage for 4 weeks. The study observed the body weight, water intake, bladder and kidney indices (to evaluate their general status), urination behavior pattern (to observe frequency and urgency), and urodynamics (to measure bladder parameters). Hematoxylin and eosin and Masson's trichome staining were used to observe changes in the bladder structure. Enzyme-linked immunosorbent assay was used to measure the levels of nerve growth factor, brain-derived neurotrophic factor, and acetylcholine in the urine. The key targets involved in these mechanisms were validated using reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, and western blot in vivo/vitro experiments. Result: Network pharmacological analysis predicted that XP may alleviate OAB by affecting the cholinergic synapse and calcium signaling pathways. XP treatment significantly reduced the bladder index, improved urine behavior and urodynamic parameters, decreased the neurotransmitters in urine, and reduced the thickness of the bladder wall and collagen ratio. These results indicate that XP can alleviate OAB symptoms and improve the bladder structure. In vivo/vitro experiments further demonstrated that XP can inhibit targets, such as muscarinic acetylcholine receptor 2, and participate in cholinergic synapses to further regulate the parasympathetic nervous system. It can also reduce the overexpression of Ca2+ caused by agonists, inhibit targets such as transient receptor potential vanilloid type 1, and participate in calcium signaling pathways to maintain Ca2+ homeostasis. Conclusion These results suggest that XP inhibited bladder overactivity by maintaining Ca2+ homeostasis and regulating the parasympathetic nervous system.

ObjectiveTo observe the effect of water extract of Mori Folium （MLE） on oxidative stress in adipose tissue of type 2 diabetes mellitus （T2DM） mice and explore its mechanism. MethodTwenty-four male db/db mice were randomly divided into model group， metformin group， low-dose MLE （MLE-L） group， and high-dose MLE （MLE-H） group according to their body weight and blood glucose， with six mice in each group， and other six C57BLKS/JGpt wild littermate mice were selected as normal group. The mice in the metformin group were given 200 mg·kg^-1 metformin suspension， and the mice in the MLE-L and MLE-H groups were respectively given 2 g·kg^-1 and 4 g·kg^-1 MLE， while the mice in the normal group and model group were given the same dose of deionized water by daily gavage for eight weeks. Body weight， subcutaneous fat index， fasting blood glucose （FBG）， and oral glucose tolerance level （OGTT） of the mice were detected， and serum superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and malondialdehyde （MDA） were measured. The expression levels of silent information regulator 1 （SIRT1） and NADPH oxidase type 4 （NOX4） protein in subcutaneous adipose tissue of the mice were detected by Western blot. ResultThe FBG level， OGTT， and subcutaneous fat index of T2DM mice were significantly decreased （P<0.05， P<0.01） after administration of MLE compared with the blank group. The contents of serum SOD and GSH were significantly increased， while the level of oxidative stress damage marker MDA was significantly decreased （P<0.05， P<0.01）. The expression of SIRT1 protein in adipose tissue was significantly increased， while the expression of NOX4 protein was significantly decreased （P<0.05， P<0.01）. ConclusionMLE can ameliorate T2DM by alleviating oxidative stress in adipose tissue of T2DM mice and reducing blood glucose.

ObjectiveTo investigate the protective effects of Mori Folium extract （MLE） on the kidney of db/db diabetic mice and its mechanism. MethodTwenty-four male C57BLKS/JGpt-Leprdb/Leprdb （db/db） mice were randomly divided into model group， metformin group， low-dose group of MLE （MLE-L）， and high-dose group of MLE （MLE-H） according to their fasting blood glucose （FBG）， with six mice in each group， and other six C57BLKS/JGpt wild littermate （m/m） mice were selected as normal group. The mice in the drug administration groups were given corresponding drugs by gavage， and the mice in the normal group and model group were given the same dose of deionized water by gavage once a day for continuous eight weeks. Body weight， bilateral kidney weight， and FBG were measured， and an oral glucose tolerance test （OGTT） was performed. The pathological changes in the kidney tissue of mice were observed by hematoxylin-eosin （HE） and periodic acid-silver （PAS） staining， and serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of tumor necrosis factor-alpha （TNF-α） and interleukin-6 （IL-6） in serum and urinary microalbumin （U-mAlb） of mice. The expression levels of toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， and nuclear factor-kappa B p65 （NF-κB p65） protein in kidney tissue of mice were tested by Western blot. ResultCompared with the normal group， the body weight， absolute renal weight， FBG， and the area under the curve （AUC） of OGTT of mice in the model group were significantly increased （P<0.01）， and the levels of SCr， BUN， and U-mAlb， as well as TNF-α and IL-6 in serum were significantly increased （P<0.01）. The glomerular basement membrane in the kidney tissue of mice was thicker， with obvious inflammatory cell infiltration. The protein expression levels of TLR4， MyD88， and NF-κB p65 in the kidney tissue of mice were increased significantly （P<0.01）. Compared with the model group， there was no statistical difference in the body weight of mice in each drug administration group. The absolute renal weight of mice in the MLE-H and metformin groups was significantly reduced （P<0.05， P<0.01）. The FBG levels of mice in the metformin， MLE-L， and MLE-H groups started to decrease after treatment for four to eight weeks （P<0.05， P<0.01）. The AUC of mice in the MLE-H and metformin groups was significantly decreased （P<0.01）. The levels of SCr， BUN， and U-mAlb of mice in the MLE-H and metformin groups were significantly decreased （P<0.01）， and those of SCr and U-mAlb of mice in the MLE-L group were significantly decreased （P<0.01）. The levels of TNF-α and IL-6 in the serum of mice in the MLE-H and metformin groups were significantly decreased （P<0.01）. The renal tissue pathology of mice in each drug administration group was improved to varying degrees， and the protein expression levels of TLR4， MyD88， and NF-κB p65 in the MLE-H group were decreased significantly （P<0.05， P<0.01）. ConclusionMLE can improve the renal structure and function of db/db diabetic mice， and its mechanism may be related to the inhibition of the TLR4/MyD88/NF-κB signaling pathway.

Mori Folium， the dried leaves of Morus alba， is widely used in clinical practice for dispersing wind and heat， clearing the lung and moistening dryness， soothing the liver and improving vision， and cooling blood and stopping bleeding. It has been used to regulate blood glucose since ancient times， and modern studies have shown that the active components of Mori Folium for lowering blood glucose mainly include flavonoids， alkaloids， polysaccharides， and phenols. These components are mainly extracted by solvents such as water and alcohols with the assistance of ultrasound and microwave. In addition， new extraction methods are emerging， such as CO₂ supercritical fluid extraction， enzymatic hydrolysis， and cloud point extraction. Mori Folium lowers blood glucose via multiple components， pathways， and targets. Specifically， it can improve glucose and lipid metabolism， protect pancreatic β cells， and alleviate insulin resistance to reduce the damage caused by hyperglycemia and restore normal physiological functions. Although a large number of studies have been carried out on diabetes， the causes and radical treatment methods remain to be explored， and diabetes is still a major disease that endangers human health and needs to be solved urgently. The articles about extraction process and mechanism of active components in Mori Folium for lowering blood glucose were retrieved from the China National Knowledge Infrastructure （CNKI）， Web of Science， and PubMed. We analyzed the applicable extraction methods for the blood glucose-lowering components such as flavonoids， polysaccharides， and alkaloids in Mori Folium， and compared the conventional and emerging methods. Furthermore， we summarized our research achievements in the extraction of active components from Mori Folium and the blood glucose-lowering effect and mechanisms. This review aims to provide theoretical support for the optimization of the extraction process， the research on the blood glucose-lowering components and mechanism， and the development of new drugs and clinical application of Mori Folium.

Objective:To analyze the efficacy of anterior cervical Hybrid surgery and posterior cervical expansive open-door laminoplasty(EODL)in the treatment of multilevel cervical spondylotic myelopathy,and to discuss the selection of surgical methods for the patients with multilevel cervical spondylotic myelopathy.Methods:The retrospective analysis was conducted of 70 patients with multilevel cervical spondylotic myelopathy who underwent surgery at Affilated Beijing Traditional Chinese Medicine Hospital of Capital Medical University from July 2017 to July 2020.Based on the different surgical methods,the patients were divided into anterior group(n=35)and posterior group(n=35).The patients in anterior group underwent Hybrid surgery[anterior cervical discectomy and fusion(ACDF)combined with artificial cervical disc replacement(ACDR)],and the patients in posterior group underwent EODL.The hospitalization time,operation time,intraoperative blood loss,and postoperative drainage volume of the patients in two groups were recorded;the efficacy was evaluated by Japanese orthopaedic association(JOA)score,JOA improvement rate,neck disability index(NDI),visual analogue scale(VAS)for pain,and postoperative satisfaction score;the complications of the patients in two groups after surgery were recorded.Results:Compared with posterior group,the intraoperative blood loss,postoperative drainage volume,hospitalization time,and operation time of the patients in anterior group were significantly decreased(P<0.01),and the preoperative score had no significant difference(P>0.05).At the final follow-up after surgery,compared with posterior group,the JOA score and JOA improvement rate of the patients in anterior group were significantly increased(P<0.01),and the NDI score and VAS score were significantly decreased(P<0.01).Compared with before surgery,the JOA scores of the patients in two groups at the final follow-up after surgery were increased(P<0.01),and the NDI and VAS scores were significant decreased(P<0.01).The postoperative satisfaction of the patients in two groups was high based on the postoperative satisfaction score.There was no significant difference in the incidence of postoperative complication of the patients between two groups(P>0.05).Conclusion:Both the anterior cervical Hybrid surgery and EODL achieve the satisfactory results in the treatment of multilevel cervical spondylotic myelopathy.Hybrid surgery has the advantages of less bleeding and shorter surgery time,and the most suitable surgical method should be chosen clinically based on the actual situation of the patients.

Objective:To explore the inhibitory mechanism of herb cake-partitioned moxibustion on tumor growth in colitis-associated colorectal cancer(CAC)based on histone lysine demethylase 4D(KDM4D). Methods:Inbred male Sprague-Dawley rats were randomly divided into a normal group,a CAC group,a herb cake-partitioned moxibustion group,and an inhibitor group.Except the normal group,rats in the other three groups were treated with azoxymethane(AOM)combined with dextran sulfate sodium(DSS)to make CAC rat models.Rats in the normal group and the CAC group did not receive interventions;rats in the herb cake-partitioned moxibustion group received moxibustion at Qihai(CV6)and bilateral Tianshu(ST25),2 cones for one point each time,once a day for 30 d with 1-day rest every week;rats in the inhibitor group received intraperitoneal injection of KDM4D inhibitor,5-chloro-8-hydroxyquinoline(5-c-8HQ),once a day for 30 d.After intervention,the general condition,colon length,tumor number and volume,and histopathological colon changes were observed.The expression of adenomatous polyposis coli(APC),axis inhibitor(Axin),cyclin D1,matrix metalloproteinase(MMP)-7 and MMP-9 mRNAs were detected by real-time quantitative polymerase chain reaction.The proliferating cell nuclear antigen(PCNA),cleaved caspase3,KDM4D,APC,and Axin proteins were detected by immunohistochemistry. Results:Compared with the normal group,the general condition was poor,the colon length was significantly shortened(P<0.01),the number and volume of colonic tumors were increased(P<0.01),the structure of glandular duct was obviously disordered with"back-to-back"and cowall phenomenon,and also high-grade adenocarcinoma formed;the protein expression levels of PCNA and KDM4D were significantly increased(P<0.01),while cleaved caspase3,APC,and Axin were significantly reduced(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were significantly increased(P<0.01),while APC and Axin were significantly reduced(P<0.01)in the CAC group.Compared with the CAC group,the general condition was improved,the length of colon was significantly increased(P<0.01),the number and volume of the colonic tumors were reduced(P<0.05),and the colon tissues showed epithelial cell proliferation with enlarged and deep staining nuclei,dysplasia and inflammatory cell infiltration;the protein expression levels of PCNA and KDM4D were significantly reduced(P<0.01),while the cleaved caspase3,APC,and Axin were significantly increased(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were reduced(P<0.05),while the APC and Axin were increased(P<0.05)in the colon tissues of rats in the herb cake-partitioned moxibustion group and the inhibitor group. Conclusion:Herb cake-partitioned moxibustion regulated abnormally expressed KDM4D in CAC rats,activated APC and Axin,the upstream molecules of Wnt/β-catenin pathway,inhibited abnormally activated downstream molecules of Wnt/β-catenin pathway.This may be a key mechanism of herb cake-partitioned moxibustion in inhibiting CAC tumor growth.

Although there are continuous progresses in economy and society, the accelerated aging process has brought widespread impacts on various aspects of society and economy in China, especially on the supply of the working-age population. Effectively addressing labor force aging has become an urgent challenge for China's economic and social development. North American countries, particularly the United States and Canada, are also facing severe aging population issues, and have entered an aging society earlier than China. These countries have alleviated labor supply shortages through proactive immigration policies, while implementing flexible retirement, reemployment of elderly individuals, and vocational training policies to effectively encourage elderly workers to remain in their jobs. Additionally, the occupational health programs of large enterprises in North America have yielded positive returns on their health investments. Building upon an overview of the current situation and corresponding measures in response to the aging working-age population in North America, this paper presented constructive recommendations to address the aging population issue in China.