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 establish a Chinese drug-related problem （DRP） classification system applicable to pharmacist-led pharmaceutical care in China， providing pharmacists with an effective and practical tool for pharmaceutical care. METHODS A multi-stage process was employed to construct the DRP classification system， including literature review and analysis， comparison of existing classification systems， refinement of classification items and framework development， two rounds of standard case validation， expert discussion， and system revision. The Fleiss′ kappa test was used to calculate the consistency coefficient κ， assessing the reliability of pharmacists participating in evaluating the classification system. An electronic questionnaire comprising six items was employed to evaluate the system’s applicability. RESULTS The constructed Chinese DRP classification system comprised six sections [problem（including potential problems）， DRP evaluation， cause （including possible causes of potential problems）， intervention， acceptance of intervention and DRP status]， with 24 primary codes and 96 secondary codes. In the first round of case validation， κ values exceeded 0.4 for all sections except “intervention” and “DRP status”. In the second round， κ values exceeded 0.4 for all sections. In the applicability evaluation of the classification system， positive ratings （“strongly agree” or “agree”） exceeded 85% for all items. Specifically， positive ratings for“the classification system can provide appropriate category selection”，“ the classification system is comprehensive”，“ the classification system is convenient to use” and “the classification system is highly satisfactory” exceeded 92%. CONCLUSIONS The Chinese DRP classification system developed demonstrates both high reliability and applicability， providing an effective and practical classification tool for pharmacists in China to conduct pharmaceutical care.

Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

Objective: To investigate the effects of curcumin on the biological behavior of oral squamous cell carcinoma (OSCC) cells and its potential molecular mechanisms, as well as to provide experimental evidence for the application of curcumin in the prevention and treatment of OSCC. Methods: All animal experiments in this study were approved by the Institutional Animal Welfare and Ethics Committee and strictly adhered to relevant animal ethics guidelines. Potential intersecting targets of curcumin and OSCC were screened using TCMSP, SwissTargetPrediction, DrugBank, and GeneCards databases, followed by construction of a protein-protein interaction network and gene ontology(GO) /Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Scratch and clone formation experiments were conducted using CAL-27 and SCC-9 cells to detect the effect of curcumin on cell migration and proliferation ability. Combining RNA sequencing analysis of differentially expressed genes, and verifying the changes in mRNA and protein expression of key cellular molecules by curcumin through real-time fluorescence quantitative PCR and Western blot, respectively. Simultaneously establish a CAL-27 xenograft BALB/c nude mouse transplant tumor model and use immunohistochemistry to detect the effect of curcumin treatment on the expression of related proteins in the transplant tumor tissue. Results: A total of 178 intersecting targets were identified, mainly enriched in the PI3K/AKT signaling pathway and lipid metabolism-related pathways. Curcumin significantly inhibited migration and colony formation of CAL-27 and SCC-9 cells in vitro. Transcriptomic analysis identified 828 differentially expressed genes enriched in lipid metabolism and PI3K/AKT pathways. Real-time fluorescence quantitative PCR showed downregulation of PIK3CA, CCND1, BCL2, and FASN, while western blot demonstrated decreased expression of p-AKT and FASN. In vivo, curcumin markedly suppressed tumor growth and reduced the expression of Ki-67, BCL2, and p-AKT in tumor tissues. Conclusion Curcumin may inhibit the migration and proliferation of OSCC cells by regulating the PI3K/AKT signaling pathway and the expression of lipid metabolism-related genes.

Glycosylation constitutes a critical, highly intricate, and diverse co- and post-translational modification characterized by the covalent attachment of sugar moieties to proteins, lipids, or small RNAs. Complex glycans are ubiquitously present across nearly all living organisms. Despite their prevalence, our comprehension of glycan diversity remains limited, likely due to the inherent challenges associated with elucidating their structural complexity. Among post-translational modifications, protein glycosylation is notably prevalent, involving the enzymatic transfer of oligosaccharides to specific amino acid residues by glycosyltransferases. This modification plays a pivotal role in modulating protein function, including participation in various biological and biochemical recognition processes. G protein-coupled receptors (GPCRs), encoded by approximately one thousand genes, share a conserved architecture comprising seven transmembrane helices interconnected by three intracellular and three extracellular loops. Representing the largest family of human membrane proteins, GPCRs regulate a vast array of physiological and pathological processes, thereby constituting the most extensive class of therapeutic targets. In mammalian systems, the majority of GPCRs undergo glycosylation predominantly at their extracellular N-terminus or extracellular loops, primarily through N-linked and O-linked glycosylation. These covalent carbohydrate modifications exert profound effects on multiple facets of GPCR biology, including endoplasmic reticulum folding and quality control, membrane trafficking and surface expression, receptor internalization and recycling or degradation, ligand binding and signal transduction, biased signaling, and receptor dimerization. Notably, glycosylation can exert both positive and negative regulatory influences on these processes. Dysregulation of GPCR glycosylation has been implicated in a range of pathological conditions, such as cancer, diabetes, and neurological disorders, underscoring its physiological and pathological significance. Aberrant glycosylation patterns may lead to dysfunctional receptor signaling, thereby contributing to disease progression. Consequently, elucidating the precise roles of glycosylation in GPCR function not only enhances fundamental understanding of receptor biology but also facilitates the development of novel therapeutic strategies targeting glycosylation pathways or specific GPCR glycoforms. Although the functional consequences of glycosylation have been investigated for several decades, delineating their exact structural underpinnings has remained challenging due to the intrinsic flexibility and heterogeneity of carbohydrate structures. Recent advances in structural biology, particularly single-particle cryo-electron microscopy (cryo-EM) and X-ray crystallography, have catalyzed a paradigm shift in our understanding of GPCR glycosylation. The integration of these sophisticated structural techniques with biochemical approaches has redefined glycosylation as a complex structural element integral to receptor function. These developments provide a molecular framework for comprehending how glycans influence receptor pharmacology and open new avenues for the rational design of glyco-engineered biologics and allosteric modulators targeting specific extracellular motifs. This mini-review concentrates on glycosylation within the GPCR superfamily, summarizing the impact of glycosylation modifications on receptor function and regulatory mechanisms, recent progress in the structural biology of GPCR glycosylation, and prospective directions for future research in this field.

ObjectiveTo evaluate the effects of modified Baohe Pill （保和丸） formula added to conventional pulmonary rehabilitation on thoracic drainage volume， chest tube duration， and peripheral blood inflammatory indices after video-assisted thoracoscopic surgery （VATS） for lung cancer. MethodsIn this randomized parallel-controlled study， 118 post-VATS patients were enrolled， with 59 cases in each group. The control group received conventional pulmonary rehabilitation， while the treatment group additionally received an oral decoction of modified Baohe Pill formula until chest tube removal and discharge. The primary outcome was total postoperative thoracic drainage volume， while the secondary outcomes included chest tube duration and inflammatory indices including the pre-treatment and post-treatment levels and relative changes in platelet-to-lymphocyte ratio （PLR）， neutrophil-to-lymphocyte ratio （NLR）， lymphocyte-to-monocyte ratio （LMR）， systemic immune-inflammation index （SII）， aggregate index of systemic inflammation （AISI）， and systemic inflammation response index （SIRI）. Adverse events during the treatment period were recorded. ResultsThe total postoperative thoracic drainage volume was 850 （430， 1410） ml in the treatment group， lower than 1085 （660， 1720） ml in the control group （P＜0.05）. Total postoperative chest tube duration was 8 （6， 11） days in the treatment group， shorter than 10 （7， 11） days in the control group （P＜0.05）， whereas the interval from enrollment to removal did not differ significantly between groups （P＞0.05）. The postoperative NLR in the treatment group was lower than that in the control group， and the relative change in NLR was greater than that in the control group （P＜0.05）. No significant between-group differences were found in post-treatment levels or relative changes of the other five inflammatory indices （P＞0.05）. No treatment-related serious adverse events were reported in either group. ConclusionModified Baohe Pill formula plus conventional pulmonary rehabilitation has lower total postoperative thoracic drainage volume， shorter total postoperative chest tube duration， and lower NLR levels in lung cancer patients following VATS， while demonstrating a more favorable safety profile than conventional pulmonary rehabilitation alone.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

ObjectiveTo investigate the effects of Maxing Kugan decoction （MKD） on inflammatory response and apoptosis in rats with oleic acid （OA）-induced acute lung injury （ALI） and explore its mechanism of action. MethodsSixty Sprague-Dawley （SD） rats were randomly assigned into six groups： a control group， a model group， a dexamethasone-treated group （2 mg·kg^-1）， and three MKD-treated groups at low， medium， and high doses （3.1， 6.2，12.4 g·kg^-1）. Each group was administered either an equivalent volume of normal saline or the corresponding concentration of MKD by gavage for seven consecutive days. The model group and each administration group were used to establish the ALI model by tail vein injection of OA （0.2 mL·kg^-1）. Twelve hours after modeling， blood gas analyses were conducted， and the wet-to-dry （W/D） weight ratio of lung tissue was measured for each group. Additionally， enzyme-linked immunosorbent assay （ELISA） was employed to quantify the levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the bronchoalveolar lavage fluid （BALF） of the rats. Cell damage and apoptosis in lung tissue were examined via hematoxylin-eosin （HE） staining and TdT-mediated dUTP-biotin nick end labeling （TUNEL） assays， and the results were subsequently scored. The expression levels of the p38 mitogen-activated protein kinase （p38 MAPK）/nuclear factor kappa-B （NF-κB） signaling pathway and apoptosis-related proteins and mRNAs were assessed using Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the control group， the model group exhibited a significant decrease in partial pressure of oxygen （PaO₂）， blood oxygen saturation （SaO₂）， and oxygenation index （PaO₂/FiO₂）， along with a marked increase in partial pressure of carbon dioxide （PaCO₂） and lung W/D ratio （P<0.01）. Additionally， levels of TNF-α， IL-6， and IL-1β in BALF were significantly elevated （P<0.01）. Histopathological analysis of lung tissue showed significant inflammatory infiltration， tissue edema， alveolar septal thickening， and apoptosis of lung tissue. Pronounced increases were observed in the mRNA expression levels of p38 MAPK， NF-κB p65， inhibitor of NF-κB （IκBα）， B-cell lymphoma-2 associated x protein （Bax）， and Caspases-3， as well as the protein expression levels of p-p38 MAPK， p-NF-κB p65， p-IκBα， Bax， Caspases-3， and cleaved Caspases-3， while the mRNA and protein expression of Bcl-2 was downregulated （P<0.01）. Compared with the model group， MKD significantly elevated PaO₂， SaO₂， and PaO₂/FiO₂ while reducing PaCO₂ and W/D ratio in rats （P<0.01）. It also greatly reduced TNF-α， IL-6， and IL-1β levels in BALF （P<0.01） and alleviated inflammatory infiltration， tissue edema， alveolar septal thickening， and apoptosis of lung tissue. Additionally， it downregulated the mRNA expression of p38 MAPK， NF-κB p65， IκBα， Bax， Caspases-3， as well as protein expression of p-p38 MAPK， p-NF-κB p65， p-IκBα， Bax， Caspases-3， and cleaved Caspases-3 in lung tissue （P<0.05， P<0.01）， while significantly upregulating mRNA and protein expression of Bcl-2 （P<0.01）. ConclusionMKD exerts a protective effect on OA-induced ALI rats， potentially through the regulation of the p38 MAPK/NF-κB signaling pathway to inhibit inflammation and apoptosis.

ObjectiveTo investigate the effects of Maxing Kugan decoction （MKD） on inflammatory response and apoptosis in rats with oleic acid （OA）-induced acute lung injury （ALI） and explore its mechanism of action. MethodsSixty Sprague-Dawley （SD） rats were randomly assigned into six groups： a control group， a model group， a dexamethasone-treated group （2 mg·kg^-1）， and three MKD-treated groups at low， medium， and high doses （3.1， 6.2，12.4 g·kg^-1）. Each group was administered either an equivalent volume of normal saline or the corresponding concentration of MKD by gavage for seven consecutive days. The model group and each administration group were used to establish the ALI model by tail vein injection of OA （0.2 mL·kg^-1）. Twelve hours after modeling， blood gas analyses were conducted， and the wet-to-dry （W/D） weight ratio of lung tissue was measured for each group. Additionally， enzyme-linked immunosorbent assay （ELISA） was employed to quantify the levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the bronchoalveolar lavage fluid （BALF） of the rats. Cell damage and apoptosis in lung tissue were examined via hematoxylin-eosin （HE） staining and TdT-mediated dUTP-biotin nick end labeling （TUNEL） assays， and the results were subsequently scored. The expression levels of the p38 mitogen-activated protein kinase （p38 MAPK）/nuclear factor kappa-B （NF-κB） signaling pathway and apoptosis-related proteins and mRNAs were assessed using Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the control group， the model group exhibited a significant decrease in partial pressure of oxygen （PaO₂）， blood oxygen saturation （SaO₂）， and oxygenation index （PaO₂/FiO₂）， along with a marked increase in partial pressure of carbon dioxide （PaCO₂） and lung W/D ratio （P<0.01）. Additionally， levels of TNF-α， IL-6， and IL-1β in BALF were significantly elevated （P<0.01）. Histopathological analysis of lung tissue showed significant inflammatory infiltration， tissue edema， alveolar septal thickening， and apoptosis of lung tissue. Pronounced increases were observed in the mRNA expression levels of p38 MAPK， NF-κB p65， inhibitor of NF-κB （IκBα）， B-cell lymphoma-2 associated x protein （Bax）， and Caspases-3， as well as the protein expression levels of p-p38 MAPK， p-NF-κB p65， p-IκBα， Bax， Caspases-3， and cleaved Caspases-3， while the mRNA and protein expression of Bcl-2 was downregulated （P<0.01）. Compared with the model group， MKD significantly elevated PaO₂， SaO₂， and PaO₂/FiO₂ while reducing PaCO₂ and W/D ratio in rats （P<0.01）. It also greatly reduced TNF-α， IL-6， and IL-1β levels in BALF （P<0.01） and alleviated inflammatory infiltration， tissue edema， alveolar septal thickening， and apoptosis of lung tissue. Additionally， it downregulated the mRNA expression of p38 MAPK， NF-κB p65， IκBα， Bax， Caspases-3， as well as protein expression of p-p38 MAPK， p-NF-κB p65， p-IκBα， Bax， Caspases-3， and cleaved Caspases-3 in lung tissue （P<0.05， P<0.01）， while significantly upregulating mRNA and protein expression of Bcl-2 （P<0.01）. ConclusionMKD exerts a protective effect on OA-induced ALI rats， potentially through the regulation of the p38 MAPK/NF-κB signaling pathway to inhibit inflammation and apoptosis.

Guided by the theory of "fire and original qi are restricted"， it is believed that original qi depletion is the root of the cutaneous immune-related adverse events （cirAEs） related to immune checkpoint inhibitors （ICIs）， and the yin fire exuberance is the branch. Among them， original qi depletion is the internal foundation of the disease， while the drug toxicity of ICIs harming original qi is the initiating factor， and exuberant yin fire is the key pathogenesis. In clinical practice， the general treatment principle advocates banking up original qi to consolidate the root and draining fire to raise yang. Buzhong Yiqi Decoction （补中益气汤） can be used to activate transportation of middle jiao （焦） and promote ascent and dispersion of clear yang， thereby restoring the balance of qi and fire， and medicinals such as Huangqin （Radix Scutellariae）， Huanglian （Rhizoma Coptidis） and Huangbai （Cortex Phellodendri Chinensis） can be supplementetd to clear and drain yin fire. At the same time， considering the accompanying symptoms such as dampness-stasis and fluids depletion， the methods of removing dampness and dispelling stasis， supplementing blood and nourishing yin should be added flexibly. This approach can provide a new perspective and treatment strategy for reducing ICIs-related cirAEs in malignant tumors.