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.

Objective: To evaluate the intervention effectiveness of co-occurrence and prevention for myopia and obesity among primary and secondary school students, so as to provide a scientific basis for the development of comprehensive intervention measures in myopia and obesity. Methods: From September 2022 to September 2023, a cluster random sampling method was used to select 6 primary schools and 6 junior high schools from Tongzhou District, Beijing. Participants were randomly assigned to an intervention group (914 before intervention and 754 after intervention) and a control group (868 before intervention and 652 after intervention), with an expected duration of one academic year. Based on the RE-AIM framework, integrate resources from families, schools, communities, and medical institutions to develop a school-based intervention technology packagefor the co-occurrence and prevention of myopia and obesity in children. The intervention group received intervention according to the comprehensive intervention technology package, while the control group did not receive any intervention measures. Relevant health indicators during the baseline period and after intervention were measured and collected, and groups were compared by Chi quest test, t-test and Wilcoxon rank sum test. Results: After intervention, the uncorrected visual acuity of primary and secondary school students in the intervention group (4.79±0.30) and the control group (4.77±0.33) both decreased compared to those before intervention (4.80±0.30, 4.90±0.32) ( t =-7.00,-5.24); the decrease in uncorrected visual acuity in the intervention group was smaller than that in the control group( t =5.33)( P <0.01). After intervention, body mass index, waist circumference, hip circumference, and body fat percentage of primary and secondary school students in the intervention group decreased compared to those before intervention. However, the changes in these indicators were not statistically significant ( t/Z =-0.03, - 0.36，- 0.30，- 0.01, P >0.05); the above indicators in the control group increased compared to those before intervention, but only hip circumference and body fat percentage showed statistically significant changes ( t/Z =2.17, 2.62, P <0.05). After intervention, both the intervention group and the control group showed increases in systolic and diastolic blood pressure compared to those before intervention(intervention group: t =2.16,5.29; control group: t =6.84,5.07); the intervention group had lower systolic and diastolic blood pressure than the control group( t = -5.27 , -2.08)( P <0.05). After intervention, the intervention and the control groups had statistically significant differences in cognitive accuracy(92.48%, 69.33%) in terms of "outdoor exercise can prevent myopia" and "having 5 servings of adult fist sized vegetables and fruits every day" ( χ 2=6.30, 7.86, P <0.05). There was a statistically significant difference in the proportion of primary and secondary school students in the intervention group (40.98%) and the control group (35.43%) for "who did not drink sugary drinks for every day in the past 7 days" ( χ 2=4.32, P <0.05). After intervention, the intervention group and the control group showed increases in "school outdoor activity duration on school days" and "outdoor activity duration on rest days" compared to those before intervention ( t/Z =-13.32,-9.71;- 2.59，-2.69）；the behavior rate of "visual acuity measurement frequency at least once every 3 months" in the intervention group (46.68%) and the control group (52.76%) increased compared to those before intervention (36.43%, 44.01%), and the increases in the intervention group were greater than that in the control group ( χ 2=17.52,11.08) ( P <0.05). Conclusions Comprehensive intervention measures have significant intervention effects on controlling the occurrence and development of comorbidity of myopia and obesity in children. It could actively promote collaboration and cooperation among families, schools, communities and medical institutions to reduce the occurrence of myopia and obesity among primary and secondary school students.

Pancreatic cancers (PCs) is a common malignant tumor with poor prognosis in the digestive system. Its main treatment methods include surgery, radiotherapy, chemotherapy, and targeted therapy. The early diagnosis rate of hidden onset of PCs is low, and most patients have already lost the opportunity to undergo surgery when diagnosed with PCs. Chemotherapy is still the main treatment for advanced PCs, but the use of chemotherapy drugs in PCs can easily lead to drug resistance. The most significant feature that distinguishes PCs from other tumors is its rich and dense matrix, which not only hinders drug penetration but also impedes the infiltration of immune cells. The above reasons have led to a very low survival rate of PCs patients. Therefore, drug delivery systems are very important in the diagnosis and treatment of PCs. They can improve drug delivery, enhance biological barrier penetration, reduce side effects, and combine multiple treatment methods. Therefore, the treatment prospects of PCs are very broad. Currently, drug delivery systems widely applied in PCs primarily include nanodrug delivery systems, tumor microenvironment-targeted drug delivery system, immunotherapy drug delivery system, gene therapy drug delivery system, and combination therapy drug delivery system that synergize multiple therapeutic modalities. Emerging drug delivery systems (DDSs) have revolutionized PCs treatment by addressing these challenges through multiple mechanisms. Nanoformulations improve drug solubility, prolong circulation time, and reduce systemic toxicity via passive/active targeting. Smart DDSs responsive to PCs-specific stimuli enable extracellular matrix degradation, tumor-associated fibroblasts reprogramming, and vascular normalization to enhance drug accessibility. Last but not least, carrier systems loaded with myeloid-derived suppressor cell inhibitors or T cell activators can reverse immunosuppression and potentiate immunotherapy efficacy. Advanced platforms co-deliver chemotherapeutics with immunomodulators, gene-editing tools, or sonodynamic agents to achieve synergistic antitumor effects. These platforms aim to address critical challenges in PCs treatment, such as enhancing drug bioavailability, overcoming stromal barriers, reprogramming immunosuppressive niches, and achieving multi-mechanistic antitumor effects. This article provides a systematic summary and prospective analysis of the current development status, latest cutting-edge advances, opportunities, and challenges of the above-mentioned drug delivery systems in the field of PCs therapy.

Objective Logistic regression model was used to analyze the risk factors of liver cancer in patients with hepatitis B virus-related cirrhosis. Methods A retrospective analysis was performed on 504 patients with hepatitis B cirrhosis who were treated in a hospital from April 2021 to April 2024. The occurrence of liver cancer was counted. The risk factors of liver cancer in patients with HBV-related cirrhosis were analyzed by logistic regression analysis. Results Among the 504 patients with hepatitis B cirrhosis, 101 patients developed liver cancer and 403 patients did not develop liver cancer, which were included in the liver cancer group (n=101) and the non-liver cancer group (n=403).. Among hepatitis B cirrhosis, the incidence rate of liver cancer was 20.04%. Compared with the non-liver cancer group, the proportion of patients with long-term drinking history, family history of liver cancer, history of diabetes mellitus, antiviral therapy, and HBV-DNA load>104 were higher in the liver cancer group (P<0.05). logistic regression analysis found that long-term drinking history (OR=3.077, 95%CI: 1.130-8.378, P=0.028), history of diabetes mellitus (OR=3.747, 95%CI: 1.765-7.954, P=0.001), no antiviral therapy (OR=3.466, 95%CI: 1.337-8.985, P=0.011) and HBV-DNA load>104 (OR=3.149, 95%CI: 1.353-7.328, P=0.008) could independently affect the occurrence of liver cancer in patients with hepatitis B cirrhosis. Conclusion According to logistic regression analysis, long-term drinking history, history of diabetes mellitus, no antiviral therapy, and HBV-DNA load>104 are risk factors for liver cancer in patients with HBV-related cirrhosis.

Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Humans ; Kidney Failure, Chronic/metabolism* ; Medicine, Chinese Traditional ; China

Chaihu and Longgu Muli Decoction has demonstrated significant efficacy in the treatment of tachyarrhythmia accompanied by anxiety and depression. However, there is a lack of standardized guidelines for its clinical application. In this study, the Chaihu and Longgu Muli Decoction was investigated through extensive research on ancient and modern literature, as well as a collection of clinical medical records. The basic information, medication details, and diagnostic information from medical records, personal experience literature, and clinical cases in the treatment of tachyarrhythmia accompanied by anxiety were extracted and analyzed to preliminarily identify the prescription characteristics and syndrome patterns. Subsequently, the Delphi method was employed to construct an item pool based on the data obtained in the first step. An expert questionnaire was prepared to collect scores and revision opinions from experts regarding these items. After statistical analysis and group discussions, a second round of questionnaires was formed by screening out certain items. This process was repeated until a final item set for the treatment of tachyarrhythmia accompanied by anxiety with Chaihu and Longgu Muli Decoction was determined. These findings provided guidance for clinical prescription practices. By extracting 71 syndromes and signs, as well as 33 tongue and pulse characteristics, the main syndrome features included palpitations, chest tightness, irritability, etc., which were basically consistent with the ancient syndromes. Through frequency analysis and group discussions, 71 items were screened out. After screening, modification, and primary and secondary division, 11 main diagnostic items and 10 secondary diagnostic items were determined. On this basis, the research team believes that Chaihu and Longgu Muli Decoction is mainly indicated for the following syndromes in the treatment of tachyarrhythmia accompanied by anxiety(palpitations, poor sleep, bitter taste, dry mouth, irritability/easily angered/anxiety/fearfulness/easily startled, red tongue with greasy yellow coating, rapid pulse, high work/life pressure, tachyarrhythmia on electrocardiogram/Holter monitor, and positive results on anxiety scale). Secondary syndromes include chest tightness, shortness of breath, feeling heavy and weak in the body, sweating, poor appetite, constipation, greasy white tongue coating, wiry pulse, slippery pulse, or knotted and intermittent pulse.
Drugs, Chinese Herbal/therapeutic use* ; Humans ; Delphi Technique ; Anxiety/complications* ; Tachycardia/psychology* ; Female ; Male ; Middle Aged ; Adult ; Aged

Forsythia suspensa is a traditional Chinese medicine and a commonly used landscaping plant. Its dried fruit is used in medicine for its functions of clearing heat, removing toxins, reducing swelling, dissipating masses, and dispersing wind and heat. It possesses extremely high medicinal and economic value. However, the genetic differentiation and diversity of its wild populations remain unclear. In this study, chloroplast genome sequences were obtained from 15 wild individuals of F. suspensa using high-throughput sequencing technology. The sequence characteristics and intraspecific variations were analyzed. The results were as follows:(1) The full length of the F. suspensa chloroplast genome ranged from 156 184 to 156 479 bp, comprising a large single-copy region, a small single-copy region, and two inverted repeat regions. The chloroplast genome encoded a total of 132 genes, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes.(2) A total of 166-174 SSR loci, 792 SNV loci, and 63 InDel loci were identified in the F. suspensa chloroplast genome, indicating considerable genetic variation among individuals.(3) Population structure analysis revealed that F. suspensa could be divided into five or six groups. Both the population structure analysis and phylogenetic reconstruction results indicated significant genetic variation within the wild populations of F. suspensa, with no obvious correlation between intraspecific genetic differentiation and geographical distribution. This study provides new insights into the genetic diversity and differentiation within F. suspensa species and offers additional references for the conservation of species diversity and the utilization of germplasm resources in wild F. suspensa.
Genome, Chloroplast ; Forsythia/classification* ; Phylogeny ; Genetic Variation ; Chloroplasts/genetics* ; Microsatellite Repeats

This study explores the basic characteristics and potential functions of the terpene synthase(TPS) gene family members in Lonicera japonica. The L. japonica TPS(LjTPS) gene family was identified and functionally analyzed using bioinformatics methods. The results showed that a total of 70 members of the LjTPS gene family were identified in L. japonica, with protein lengths ranging from 130 to 1 437 amino acids. Most of these proteins were hydrophilic, and they were unevenly distributed across nine chromosomes. Phylogenetic analysis showed that the LjTPS gene family members were divided into six subfamilies, mainly consisting of members from the TPS-a, TPS-b, and TPS-e subfamilies. Promoter cis-acting element analysis showed that LjTPS members contained a large number of stress-responsive cis-acting elements. Aphid inoculation experiments showed that key enzyme genes in the MVA pathway for terpenoid backbone synthesis in L. japonica, such as HMGS, HMGR, MK, MPD, and the key enzyme gene in the DXP pathway, DXS, exhibited an initial increase followed by a decrease under aphid stress. The qRT-PCR analysis showed that the expression levels of the α-farnesene synthase genes LjTPS34 and LjTPS39 were down-regulated, while the expression levels of(E)-β-caryophyllene synthase genes LjTPS15 and LjTPS17 were up-regulated 12 h before aphid feeding, then began to decline. Farnesyl pyrophosphate synthase(FPS), which interacted with these genes, also displayed a pattern of increasing followed by decreasing expression. The expression of linalool synthase genes LjTPS12 and LjTPS33 was significantly up-regulated after 72 h of aphid feeding(P<0.000 1), reaching 24.39 and 22.64 times the initial expression, respectively. This pattern was in close alignment with the trend of linalool content in L. japonica. This study provides a theoretical foundation for future research on the interaction between L. japonica and pests, as well as on the functional roles of the LjTPS gene family.
Animals ; Aphids/physiology* ; Alkyl and Aryl Transferases/chemistry* ; Lonicera/parasitology* ; Phylogeny ; Plant Proteins/chemistry* ; Gene Expression Regulation, Plant ; Multigene Family ; Terpenes/metabolism*

This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*