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 improve the efficiency and standardization of preoperative anemia diagnosis and treatment by establishing a systematic intelligent management platform for preoperative anemia. Methods: A multidisciplinary collaborative model was adopted to develop a preoperative anemia management system that integrates intelligent early warning, standardized treatment pathways, and quality control. The system utilizes natural language processing technology to automatically capture laboratory data and establish evidence-based medical decision support functions. A pre-post study design was employed to compare changes in preoperative anemia screening rates, preoperative anemia intervention rates, reasonable use of iron supplements, and perioperative red blood cell transfusion rates before and after system implementation. Results: After system implementation, the standardization of anemia diagnosis and treatment significantly improved: 1) Screening effectiveness: The anemia screening rate increased to 50.00% (an increase of 27.24%); 2) Intervention effectiveness: The anemia treatment rate rose to 56.30% (an increase of 14.02%); 3) Treatment standardization: The reasonable use rate of iron supplements increased to 55.33% (an increase of 21.02%); the red blood cell transfusion rate decreased to 18.29% (a decrease of 4.07%), and the amount of red blood cell transfusions was reduced by 291 units. Conclusion: This system achieves full-process management of preoperative anemia through information technology, significantly enhancing the standardization of diagnosis and treatment as well as intervention effectiveness, providing an effective solution for perioperative anemia management.

Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
Animals ; Panax/chemistry* ; Ginsenosides/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Mice ; Male ; Alkaloids/pharmacology* ; Coptis/chemistry* ; Drug Synergism ; Insulin Resistance ; Mice, Inbred C57BL ; Humans ; Transcriptome/drug effects* ; Blood Glucose/metabolism* ; Hypoglycemic Agents/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Hepatocytes/metabolism*

Aiming at the current situation of insufficient integration of medical humanities teaching and clinical practice,as well as the need for further research and improvement in the teaching system,guided by the concept of medicine and humanistic literacy integration advocated by the new medical science,this paper deeply discussed the construction of clinical medical humanities teaching system from four aspects,including the selection of clinical medical humanities teachers and team building;the teaching path that combines theoretical education,narrative medicine,and clinical skill training infused with medical humanities content;curriculum ideological and political construction with the goal of establishing the core concept and value orientation of"patient-centered";the teaching assessment and evaluation method characterized by formative evaluation.The clinical medical humanities teaching system emphasizes the practicality,experiential,and emotional aspects of medical humanities teaching,deeply integrating medical humanities with clinical practice teaching content throughout the clinical internship period of medical education,with a view to enhancing the humanistic practice ability and literacy of medical students.

Objective:To compare the clinical value of digital breast tomosynthesis (DBT) localization and stereotactic positioning biopsy of breast lesions.Methods:This study was a cross-sectional study. Totally of 250 patients who underwent breast biopsy at Shenzhen People′s Hospital, Luohu District People′s Hospital and Peking University Shenzhen Hospital between August 2021 to October 2023 was analyzed retrospectively, including 136 cases of DBT-guided biopsy (DBT-guided group) and 114 cases of stereotactic-guided biopsy (stereotactic-guided group). The stereotactic-guided biopsy methods included core needle biopsy (CNB) and wire positioning. The DBT-guided biopsy methods included CNB, wire positioning and vacuum-assisted breast biopsy (VABB). The χ2 test or Mann-Whitney U test was used to compare the puncture success rate, operation time, localization time, puncture time, number of first valid localization phases obtained, number of exposures, and complications of different biopsy methods between 2 groups. Results:In the wire positioning biopy, the puncture success rate was 100% (33/33) in DBT-guided group and 96% (48/50) in the stereotactic-guided group, with no statistically significant difference between the two groups ( P=0.515). Compared to the stereotactic-guided group, the operation time and localization time were shorter, and the number of first valid localization phases obtained, number of exposures were fewer in the DBT-guided group( P<0.05). The incidence of complications was lower in both the DBT-guided group and the stereotactic-guided group, with no statistically significant difference ( P=0.871). In CNB, both the DBT-guided group and the stereotactic-guided group had higher puncture success rates, with no statistically significant difference ( P=0.080). Compared to the stereotactic-guided group, the operation time, localization time and puncture time were shorter, and the number of first valid localization phases obtained, number of exposures were lower in the DBT-guided group, and the difference between the two groups were statistically significant ( P<0.05). The incidence of complications was lower in both the DBT-guided group and the stereotactic-guided group, with no statistically significant difference ( P=0.627). Twenty-one cases received DBT-guided VABB, with an operation time of (19.90±3.38) min, a localization time of 6.00 (6.00, 7.00) min, a puncture time of (13.42±3.28) min, the number of first effective localization phases obtained was 1.00 (1.00, 1.00) time, the number of exposures was 4.00 (3.50, 5.00) times, and one case experienced severe pain after puncture. Conclusion:Compared with stereotactic-guided biopsy, DBT-guided biopsy can reduce operation time and exposure times, and can target more types of breast lesions, with higher clinical application value.

Panax ginseng(PG)and Panax notoginseng(PN)are highly valuable Chinese medicines(CM).Although both CMs have similar active constituents,their clinical applications are clearly different.Over the past decade,RNA sequencing(RNA-seq)analysis has been employed to investigate the molecular mechanisms of extracts or monomers.However,owing to the limited number of samples in standard RNA-seq,few studies have systematically compared the effects of PG and PN spanning multiple conditions at the transcriptomic level.Here,we developed an approach that simultaneously profiles transcriptome changes for multiplexed samples using RNA-seq(TCM-seq),a high-throughput,low-cost workflow to molecularly evaluate CM perturbations.A species-mixing experiment was conducted to illustrate the accuracy of sample multiplexing in TCM-seq.Transcriptomes from repeated samples were used to verify the robustness of TCM-seq.We then focused on the primary active components,Panax notoginseng sa-ponins(PNS)and Panax ginseng saponins(PGS)extracted from PN and PG,respectively.We also char-acterized the transcriptome changes of 10 cell lines,treated with four different doses of PNS and PGS,using TCM-seq to compare the differences in their perturbing effects on genes,functional pathways,gene modules,and molecular networks.The results of transcriptional data analysis showed that the tran-scriptional patterns of various cell lines were significantly distinct.PGS exhibited a stronger regulatory effect on genes involved in cardiovascular disease,whereas PNS resulted in a greater coagulation effect on vascular endothelial cells.This study proposes a paradigm to comprehensively explore the differences in mechanisms of action between CMs based on transcriptome readouts.

OBJECTIVE: Flavonoids are the bioactive compounds in safflower (Carthamus tinctorius), in which chalcone synthase (CHS) is the first limiting enzyme. However, it is unclear that which chalcone synthase genes (CHSs) are participated in flavonoids biosynthesis in C. tinctorius. In this study, the CHSs in the molecular characterization and enzyme activities were investigated. METHODS: Putative chalcone biosynthase genes were screened by the full-length transcriptome sequences data in C. tinctorius. Chalcone biosynthase genes in C. tinctorius (CtCHSs) were cloned from cDNA of flowers of C. tinctorius. The cloned gene sequences were analyzed by bioinformatics, and their expression patterns were analyzed by real-time PCR (RT-PCR). The protein of CtCHS in the development of flowers was detected by polyclonal antibody Western blot. A recombinant vector of CtCHS was constructed. The CtCHS recombinant protein was induced and purified to detect the enzyme reaction (catalyzing the reaction of p-coumaryl-CoA and malonyl-CoA to produce naringin chalcone). The reaction product was detected by HPLC and LC-MS. RESULTS: Two full-length CtCHS genes were successfully cloned from the flowers of safflower (CtCHS1 and CtCHS3), with gene lengths of 1525 bp and 1358 bp, respectively. RT-PCR analysis showed that both genes were highly expressed in the flowers, but the expression of CtCHS1 was higher than that of CtCHS3 at each developmental stage of the flowers. WB analysis showed that only CtCHS1 protein could be detected at each developmental stage of the flowers. HPLC and LC-MS analyses showed that CtCHS1 could catalyze the conversion of p-coumaryl-CoA and malonyl-CoA substrates to naringin chalcone. CONCLUSION CtCHS1 is involved in the biosynthesis of naringin chalcone in safflower.

Pharmacodynamics material basis and effective mechanisms are the two main issues to decipher the mechnisms of action of Traditional Chinese medicines (TCMs) for the treatment of diseases. TCMs, in "multi-component, multi-target, multi-pathway" paradigm, show satisfactory clinical results in complex diseases. New ideas and methods are urgently needed to explain the complex interactions between TCMs and diseases. Network pharmacology (NP) provides a novel paradigm to uncover and visualize the underlying interaction networks of TCMs against multifactorial diseases. The development and application of NP has promoted the safety, efficacy, and mechanism investigations of TCMs, which then reinforces the credibility and popularity of TCMs. The current organ-centricity of medicine and the "one disease-one target-one drug" dogma obstruct the understanding of complex diseases and the development of effective drugs. Therefore, more attentions should be paid to shift from "phenotype and symptom" to "endotype and cause" in understanding and redefining current diseases. In the past two decades, with the advent of advanced and intelligent technologies (such as metabolomics, proteomics, transcriptomics, single-cell omics, and artificial intelligence), NP has been improved and deeply implemented, and presented its great value and potential as the next drug-discovery paradigm. NP is developed to cure causal mechanisms instead of treating symptoms. This review briefly summarizes the recent research progress on NP application in TCMs for efficacy research, mechanism elucidation, target prediction, safety evaluation, drug repurposing, and drug design.
Drugs, Chinese Herbal/pharmacology* ; Network Pharmacology ; Artificial Intelligence ; Medicine, Chinese Traditional ; Metabolomics

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Objective:To investigate the expression difference of miR-3189-3p in renal cancer tissue and adjacent tissue and its effect on the biological function of renal cancer cells.Methods:quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of miR-3189-3p in renal cancer tissues and adjacent tissues, renal cancer cell lines (Caki-1, ACHN, A498, OS-RC-2) and normal renal tubular epithelial cells HK-2. miR-NC or miR-3189-3p mimics were transfected into renal cancer cells with the lowest expression of miR-3189-3p, respectively, named miR-NC group and miR-3189-3p group. The effects of miR-3189-3p on the proliferation and invasion of renal cancer cells were detected by CCK-8 method and Transwell migration experiment. miRanda and miRTarBase software was used to predict the downstream gene of miR-3189-3p. The dual luciferase reporter gene experiment was used to verify the downstream gene of miR-3189-3p. qRT-PCR and Western blotting were used to detect the expression of miR-3189-3p downstream gene. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between groups. Results:The relative expression of miR-3189-3p in renal cancer tissue and paracancerous tissue was 1.97±0.61 and 6.19±0.73, respectively, and the relative expression of miR-3189-3p in renal cancer tissue was lower than that in paracancerous tissue ( P<0.01). The relative expression of miR-3189-3p in renal cancer cell lines was lower than that in HK-2 cells ( P<0.05). The relative expression of miR-3189-3p in OS-RC-2 cells was the lowest ( P<0.01). The relative expression levels of miR-3189-3p in OS-RC-2 cells in the miR-NC group and miR-3189-3p group were 1.01±0.11 and 9.27±1.43, respectively, and the relative expression levels of miR-3189-3p in the miR-NC group significantly lower than the miR-3189-3p group ( P<0.01). Compared with the miR-NC group, the proliferation ability of OS-RC-2 cells with high expression of miR-3189-3p was significantly reduced ( P<0.05). The numbers of penetrating cells in the miR-NC group and miR-3189-3p group were 165.40±17.02 and 41.07±6.36, respectively, and the invasive ability of OS-RC-2 cells in the miR-3189-3p group was significantly reduced ( P<0.01). The target gene of miR-3189-3p is Aquaporin 3 ( AQP3) and miR-3189-3p can target AQP3 mRNA ( P<0.01). Compared with the miR-NC group, the expression of AQP3 gene in the high-expressing miR-3189-3p cells was significantly reduced at both the mRNA level and the protein level ( P<0.01). Conclusions:The expression of miR-3189-3p is down-regulated in renal cell carcinoma. High expression of miR-3189-3p can significantly inhibit the proliferation and invasion of renal cell carcinoma OS-RC-2 cells. The molecular mechanism is that miR-3189-5p targets and inhibits the expression of AQP3 gene.