OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Objective To explore the predictive value of combined serum soluble hemoglobin scavenger receptor 163(sCD163),hypersensitive C-reactive protein(hs-CRP),and procalcitonin(PCT)for stroke-associated pneumonia(SAP).Methods A total of 100 patients with acute ische-mic stroke admitted to the First Hospital of Zhangjiakou from October 2021 to January 2023 were se-lected as the study subjects.According to whether they developed SPA within 7 days of admission,they were divided into SAP group(n=64)and non-SAP group(n=36).Based on pneumonia se-verity index(PSI),patients in the SAP group were further divided into mild SAP group and severe SAP group.Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum levels of sCD163,hs-CRP,and PCT.The clinical data of the patients were collected and compared.Pearson's method was used to analyze the correlation between the PSI score and the serum levels of sCD163,hs-CRP,and PCT in SAP patients.Multivariate Logistic regression analysis was employed to screen for factors influencing the occurrence of SAP.Receiver operating characteristic(ROC)curve analy-sis was used to evaluate the predictive efficacy of serum sCD163,hs-CRP,and PCT for the occur-rence of SAP.Results The proportion of patients with dysphagia and the National Institutes of Health Stroke Scale(NIHSS)score in the SAP group were significantly higher than those in the non-SAP group(P＜0.05).The serum levels of sCD163,hs-CRP,and PCT in the SAP group were significantly higher than those in the non-SAP group(P＜0.05).The serum levels of sCD163,hs-CRP,and PCT in the severe SAP group were significantly higher than those in the mild SAP group(P＜0.05).Pearson's correlation analysis showed that the PSI score was positively correlated with the serum levels of sCD163,hs-CRP and PCT in SAP patients(r=0.356,0.413,0.391,P＜0.001).Logistic regression analysis revealed that serum sCD163,hs-CRP,PCT,NIHSS score,and dysphagia were all influencing factors for the occurrence of SAP(P＜0.05).The areas under the curve(AUC)for predicting SAP using serum sCD163,hs-CRP,PCT and their combina-tion were 0.842,0.924,0.866 and 0.973,respectively,with sensitivities of 73.44％,84.37％,67.19％and 90.62％,and specificities of 88.89％,83.33％,97.22％and 94.44％,respectively.The predictive value of the combined detection was superior to that of the individual detection of ser-um sCD163,hs-CRP and PCT(P＜0.05).Conclusion The serum levels of sCD163,hs-CRP,and PCT are elevated in SAP patients,and their changes are closely related to the severity of the disease.The combined detection of these three indicators has a high value in predicting the occur-rence of SAP and may serve as auxiliary markers for predicting early SAP.

This paper summarized the clinical experience of CHEN Tongyun in the treatment of postinflammatory dyspigmentation with the method of unblocking and nourishing qi and blood. It is believed that the core pathogenesis of this disease is poor qi movement and skin blood stasis， for which the method of unblocking and nourishing qi and blood should be used. Postinflammatory pigmentation on the face is mainly caused by qi stagnation and blood stasis， and it is suggested to regulate liver and spleen， move qi and invigorate blood usually with modified Tonghua Decoction （通化汤）. Postinflammatory hypopigmentation is mainly due to qi and blood depletion， for which the treatment should be fortifying the spleen and strengthening kidney， replenishing qi and generating blood， and modified Yangfu Decoction （养复汤） is commonly used. Simultaneously， medicinals of ascending and descending functions， moving qi and blood， warming yang and nourishing yin should be combined， and the results from modern pharmacological research should be considered.

ObjectiveTo explore whether the mechanism of Shuangshen Ningxin capsules （SSNX） in alleviating myocardial ischemia-reperfusion injury （MIRI） in rats is related to the regulation of mitochondrial fission and fusion. MethodThis study focused on Sprague Dawley （SD） rats and ligated the left anterior descending branch of the coronary artery to construct a rat model of MIRI. The rats were divided into the sham operation group， model group， SSNX group （90 mg·kg^-1） and trimetazidine group （5.4 mg·kg^-1）. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） were detected by micro method. Changes in mitochondrial membrane potential （△Ψm） and the degree of mitochondrial permeability transition pore （mPTP） opening were detected by the chemical fluorescence method. The intracellular adenosine triphosphate （ATP） level was detected by the luciferase assay. The messenger ribonucleic acid （mRNA） and protein expression levels of mitochondrial fission and fusion related factors dynamin-related protein 1 （DRP1）， mitochondrial fission 1 protein （FIS1）， optic atrophy protein 1 （OPA1）， mitochondrial outer membrane fusion protein 1 （MFN1）， and MFN2 were detected by real-time polymerase chain reaction （real-time PCR） and Western blot. ResultCompared with the sham operation group， the model group showed a decrease in serum SOD activity and an increase in MDA content. The opening level of mPTP， the level of △Ψm and ATP content decreased， the protein expressions of mitochondrial fission factors DRP1 and FIS1 increased， and the protein expressions and mRNA transcription levels of fusion related factors OPA1 and MFN1 decreased. Compared with the model group，SSNX significantly increased serum SOD activity， reduced MDA content， increased intracellular ATP level and △Ψm， reduced the opening level of mPTP， downregulated the protein expressions of mitochondrial fission factors DRP1 and FIS1， and increased the mRNA transcription levels and protein expressions of fusion related factors OPA1 and MFN1. ConclusionSSNX inhibits the expressions of mitochondrial fission factors DRP1 and FIS1， and increases the expressions of fusion related factors OPA1 and MFN1， inhibiting mitochondrial fission and increasing mitochondrial fusion， thereby alleviating MIRI.

ObjectiveTo describe the epidemic characteristics of COVID-19 after policy adjustment from “Category B notifiable disease with category A management” to “Category B notifiable disease with category B management”， and to explore the protective effect of previous infection with SARS-CoV-2 on common symptoms of reinfection. MethodsHealthcare workers infected with SARS-CoV-2 in a grade A tertiary hospital in Shanghai were included in the study from December 4， 2022 to January 11， 2023. Data on demographic characteristics， clinical symptoms， medical history， and COVID-19 vaccination history were collected. We determined the epidemiological curve and characteristics， and then compared the difference in the severity of clinical symptoms between primary and reinfection subjects. ResultsA total of 2 704 cases were included in the study， of which 45 had reinfection， 605 （22.4%）were males， 608 （22.5%）were doctors， 1 275 （47.2%） were nurses， and 2 351 （86.9%） received ≥3 doses of COVID-19 vaccination. The average age of these healthcare workers was （34.9±9.1） years old. The number of cases with mild/moderate illness， asymptomatic infection， fever， headache， dry cough， expectoration， and chest tightness were 2 704 （100.0%）， 92 （3.4%）， 2 385 （88.2%）， 2 066 （76.4%）， 1 642 （60.7%）， 1 807 （66.8%）， and 439 （16.2%）， respectively. Reinfection was a protective factor for fever （OR=0.161， P<0.001）， headache （OR=0.320， P<0.001）， and peak body temperature （β=-0.446， P<0.001）. ConclusionFollowing the COVID-19 policy adjustment as a category B notifiable disease， healthcare workers at a grade A tertiary hospital in Shanghai predominantly experiences mild to moderate COVID-19 symptoms. Reinfection results in milder clinical manifestations， with a lower proportion of being asymptomatic.

Objective To detect the serum levels of CC chemokine receptor 2(CCR2)and C-reactive pro-tein(CRP)in stroke patients,and analyze their relationship with the severity of stroke associated pneumonia and their clinical significance.Methods A total of 78 patients with stroke associated pneumonia who were di-agnosed and treated in the hospital from October 2022 to February 2023 were collected as the study group,ac-cording to the severity of pneumonia,the study group was divided into mild group(31 cases),moderate group(29 cases),and severe group(18 cases),78 stroke patients who did not develop pneumonia were included into control group.Pearson method was applied to analyze the correlation between serum CCR2 and CRP levels in stroke associated pneumonia patients.Multivariate Logistic regression was applied to analyze the factors influ-encing the occurrence of stroke associated pneumonia.Receiver operating characteristic(ROC)curve was ap-plied to analyze the diagnostic value of serum CCR2 and CRP for stroke associated pneumonia.Results The National Institute of Health stroke scale(NIHSS)score,serum CCR2,and CRP levels in the study group were obviously higher than those in the control group(P<0.05).The levels of serum CCR2 and CRP increased with the aggravation of pneumonia(P<0.05).The levels of serum CCR2 and CRP in the study group were positively correlated(r=0.799,P<0.05).NIHSS score,CCR2,and CRP levels were risk factors for stroke associated pneumonia in stroke patients(P<0.05).The area under the curve(AUC)for the diagnosis of stroke associated pneumonia using serum CCR2 and CRP alone was 0.873 and 0.888,respectively,and the AUC for the combined detection of the two was 0.936,the combined detection of the two was superior to the individual detection of serum CCR2 and CRP(Zcombination-CCR2=1.987,Zcombination-CRP=1.832,P=0.041,0.047).Conclusion Serum CCR2 and CRP are closely related to the severity of stroke associated pneumonia,and their combined detection has high diagnostic value for stroke associated pneumonia.

【Objective】 To investigate the anemia status of infants and toddlers aged 6 - 24 months in Linxia Hui Autonomous Prefecture, Gansu Province, and to comprehensively evaluate the differences in feeding behaviors between anaemic and normal children through the infant and child feeding index (ICFI) and feeding knowledge scores, so as to provide reference for the guidance of infants and young children feeding in ethnic minority areas and the promotion of children′s growth and development. 【Methods】 Taking infants and young children aged 6 - 24 months in Linxia Prefecture as the study subjects, a multi-stage random sampling method was used to select children who met the requirements from 5 townships and 5 villages in 7 counties in 2019 and 2020.Periphral blood samples were collected to test the level of hemoglobin, so as to determine the anemia status.Meanwhile, physical examination was performed and a questionnaire survey of guardians was conducted to analyze the association betweenanaemia and feeding patterns 【Results】 A total of 3 901 infants and children were included in this study, of whom 729 (18.70%) were anaemic, with a mean ICFI score of 12.56±2.70 and a mean feeding knowledge score of 1.97±1.01.There was no statistically significant association of low feeding knowledge score and low ICFI with anaemia after adjusting for confounders (P>0.05), Unqualified meat addition in ICFI was a risk factor for anaemia (OR=1.355, P=0.042), while non-bottle feeding in the past 24 hours (OR=0.762, P=0.021), and breastfeeding in the past 24 hours of infants and toddlers aged 12 - 24 months (OR=0.228, P=0.018) were protective factor for anemia in infants and toddlers aged 12 - 24 months. 【Conclusions】 The average prevalence of anemia in infants and toddlers aged 6 - 24 months in Linxia Hui Autonomous Prefecture of Gansu Province is high, but the level of infant feeding and the level of feeding knowledge of caregivers are low.Early adherence to breastfeeding, timely addition of supplementary food, and more comsumpution of meat for children are conducive to preventing anemia.