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.

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.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， to identify the in vivo and in vitro chemical components of total phenolic acids in Gei Herba（TPAGH）， and to clarify the pharmacological effects and potential mechanisms of the effective part in promoting acute wound healing and inhibiting scar formation. MethodsUPLC-Q-Orbitrap-MS was used to identify the chemical components of TPAGH and ingredients absorbed in vivo after topical administration. A total of 120 ICR mice were randomly divided into the model group， recombinant human epidermal growth factor（rhEGF） group（4 mg·kg^-1）， and low， medium， and high dose groups of TPAGH（3.5， 7， 14 mg·kg^-1）， with 24 mice in each group. A full-thickness skin excision model was constructed， and each administration group was coated with the drug at the wound site， and the model group was treated with an equal volume of normal saline， the treatment was continued for 30 days， during which 8 mice from each group were sacrificed on days 6， 12， and 30. The healing of the wounds in the mice was observed， and histopathological changes in the skin tissues were dynamically observed by hematoxylin-eosin（HE）， Masson， and Sirius red staining， and enzyme-linked immunosorbent assay（ELISA） was used to dynamically measure the contents of interleukin-6（IL-6）， tumor necrosis factor-α（TNF-α）， vascular endothelial growth factor A（VEGFA）， matrix metalloproteinase（MMP）-3 and MMP-9 in skin tissues. Network pharmacology was used to predict the targets related to the promotion of acute wound healing and the inhibition of scar formation by TPAGH， and molecular docking of key components and targets was performed. Gene Ontology（GO） biological process analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were carried out for the related targets， so as to construct a network diagram of herbal material-compound-target-pathway-pharmacological effect-disease for further exploring its potential mechanisms. ResultsA total of 146 compounds were identified in TPAGH， including 28 phenylpropanoids， 31 tannins， 23 triterpenes， 49 flavonoids， and 15 others， and 16 prototype components were found in the serum of mice. Pharmacodynamic results showed that， compared with the model group， the TPAGH groups showed a significant increase in relative wound healing rate and relative scar inhibition rate（P<0.05）， and the number of new capillaries， number of fibroblasts， number of new skin appendages， epidermal regeneration rate， collagen deposition ratio， and Ⅲ/Ⅰ collagen ratio in the tissue were significantly improved（P<0.05， 0.01）， the levels of IL-6， TNF-α， MMP-3 and MMP-9 in the skin tissues were reduced to different degrees， while the level of VEGFA was increased. Network pharmacology analysis screened 10 core targets， including tumor protein 53（TP53）， sarcoma receptor coactivator（SRC）， protein kinase B（Akt）1， signal transducer and activator of transcription 3（STAT3）， epidermal growth factor receptor（EGFR） and so on， participating in 75 signaling pathways such as advanced glycation end-products（AGE）-receptor for AGE（AGE/RAGE） signaling pathway， phosphatidylinositol 3-kinase（PI3K）/Akt signaling pathway， mitogen-activated protein kinase（MAPK） signaling pathway. Molecular docking confirmed that the key components genistein， geraniin， and casuariin had good binding ability to TP53， SRC， Akt1， STAT3 and EGFR. ConclusionThis study comprehensively reflects the chemical composition of TPAGH and the absorbed components after topical administration through UPLC-Q-Orbitrap-MS. TPAGH significantly regulates key indicators of skin healing and tissue reconstruction， thereby clarifying its role in promoting acute wound healing and inhibiting scar formation. By combining in vitro and in vivo component identification with network pharmacology， the study explores how key components may bind to targets such as TP53， Akt1 and EGFR， exerting therapeutic effects through related pathways such as immune inflammation and vascular regeneration.

Nonspecific orbital inflammation(NSOI)is an orbital inflammation that is not associated with an infection. Even though it's often considered the most common diagnosis in orbital biopsies, it's still an exclusionary diagnosis that means systemic illnesses and other possible causes have to be ruled out. Though it is always an excluded clinical diagnosis, acute orbital symptoms such discomfort, exophthalmos, periorbital edema, chemosis, diplopia, and vision impairment are commonly associated with NSOI. Clinical diagnosis and management of NSOI provide a substantial difficulty. There are presently no recognized diagnostic criteria or standard treatment strategy for NSOI, and the clinical symptoms and histological features show significant variation. This guide was formulated under the auspices of the Ocular Oncology Committee of the Opthalmology Branch of the Chinese Medical Doctor Association, Opthalmology Committee of International Association of Intelligent Medicine, Opthalmology Committee of International Association of Translational Medicine making a detailed summary of the definition, classification, diagnosis and treatment of the NSOI, with a view to aiding clinicians to improve diagnostic efficiency and formulate a better treatment plan for patients.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), primarily manifesting as motor dysfunctions such as resting tremor, muscle rigidity, and bradykinesia. According to the classical model of basal ganglia motor control, approximately half of the medium spiny neurons (MSNs) in the striatum are D1-MSNs, which constitute the direct pathway. These neurons express D₁-dopamine receptor (D₁R) and substance P, and they mainly participate in the selection, initiation, and execution of movements. The other half are D2-MSNs, which constitute the indirect pathway. These neurons express D₂-dopamine receptor (D₂R) and adenosine 2A receptors and are involved in inhibiting unnecessary movements or terminating ongoing movements, thereby adjusting movement sequences to perform more precise motor behaviors. The direct pathway in the striatum modulates the activity of motor cortex neurons by exciting D1-MSNs through neurotransmitters such as glutamate (Glu), allowing the motor cortex to send signals more freely to the motor system, thus facilitating the generation and execution of specific motor behaviors. Studies using D1-Cre and D2-Cre mice with neurons labeled for D₁R and D₂R have shown that both types of neurons are involved in the execution of movements, with D1-MSNs participating in movement initiation and D2-MSNs in inhibiting actions unrelated to the target movement. These findings suggest that the structural and functional plasticity of D1-MSNs and D2-MSNs in the basal ganglia circuitry enables motor learning and behavioral regulation. Additionally, when SNpc DA neurons begin to degenerate, D1-MSNs are initially affected but do not immediately cause motor impairments. In contrast, when D2-MSNs undergo pathological changes, they are first activated by upstream projecting neurons, leading to the inhibition of most motor behaviors and resulting in motor dysfunction. Therefore, it is hypothesized that motor impairments such as bradykinesia and initiation difficulties are more closely related to the functional activity of D2-MSNs. The extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) signaling pathway has been identified as a critical modulator in the pathophysiology of PD. Recent findings indicate that Erk/MAPK signaling pathway can mediate DA and Glu signaling in the central nervous system, maintaining normal functional activity of striatal MSNs and influencing the transmission of motor control signals. Within this complex regulatory network, the Erk/MAPK signaling pathway plays a key role in transmitting motor information to downstream neurons, regulating normal movements, avoiding unnecessary movements, and finely tuning motor behaviors. Our laboratory’s previous research found that 4 weeks of aerobic exercise intervention improved motor dysfunction in PD mice by inhibiting the Erk1/2 signaling upstream of striatal MSNs, primarily involving the Erk1/2 signaling in D2-MSNs rather than D1-MSNs. This review summarizes the neurobiological mechanisms of Erk/MAPK signaling pathway in D2-MSNs for the prevention and treatment of motor dysfunction in PD. By exploring the role of this signaling pathway in regulating motor abnormalities and preventing motor dysfunction in the central nervous system of PD, this review provides new theoretical perspectives for related mechanistic research and therapeutic strategies.

ObjectiveBased on analytic hierarchy process（AHP）-criteria importance through intercriteria correlation（CRITIC） hybrid weighting method， grey relational analysis and backpropagation artificial neural network（BP-ANN）， to optimize the water extraction process of Qizhi prescription， so as to provide an experimental basis for optimization of the preparation process of this prescription and the establishment of quality standards. MethodsL₉（3⁴） orthogonal test was employed， and the AHP-CRITIC hybrid weighting method was utilized to determine the weight coefficients of the quality fractions of various components， including astragaloside Ⅳ， polygalaxanthone Ⅲ， calycosin-7-O-β-D-glucoside， tenuifolin， and 3，6′-disinapoylsucrose， as well as the dry extract yield. The comprehensive score of each factor level combination in the orthogonal test were calculated as evaluation indicator to select the optimal extraction process parameters. The effects of extraction times， extraction time， and solvent dosage on the aqueous extraction process of the formula were investigated through intuitive analysis， variance analysis， and grey relational analysis. Meanwhile， a BP-ANN model was established to reverse-predict the optimal extraction process parameters of Qizhi prescription， and the optimized process parameters were validated. ResultsThe weight coefficients of the five index components（astragaloside Ⅳ， tenuifolin， calycosin-7-O-β-D-glucoside， polygalaxanthone Ⅲ， and 3，6′-disinapoylsucrose） and dry extract yield were 25.7%， 20.82%， 16.41%， 12.45%， 15.96% and 8.67%， respectively. The optimized extraction process parameters were extracted 3 times with 8， 6， 6 times the amount of water， each time for 1 h. The network prediction results of BP-ANN test samples were consistent with the orthogonal test results， and the mean square error（MSE） of the predicted and measured values of the network was <1%. The water extraction process of Qizhi prescription analyzed and predicted by relevant mathematical models was stable and feasible， which could effectively improve the extraction efficiency of the active ingredients of Astragali Radix and Polygalae Radix， and the average comprehensive score of the validation test was 90.85 with the relative standard deviation（RSD） of 1.55%. ConclusionThis study establishes a water extraction process for compound Qizhi granules， and the optimized extraction process can effectively improve the extraction efficiency of active ingredients， which provides useful references for the optimization of preparation process and the establishment of quality standards for other clinical experience formulas.

Five saponins were isolated from the kernels of Momordica cochinchinensis, by macroporous resin, silica gel, ODS column chromatography, and semi preparative HPLC. Based on MS and NMR analysis, combining with alkaline hydrolysis and acid hydrolysis, their structures were identified as: gypsogenin-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (1), quillaic acid-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (2), gypsogenin-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (3), quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (4), 18α-quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside (5). Compounds 1-5 were new compounds, and named as mubezhisides A, B, C, D, E, respectively. They all could obviously inhibited the growth of Candida albicans, C. parapsilosis, and C. tropicalis.

Background Prior epidemiological studies suggest that exposure to pyrethroid insecticides may adversely affect children’s respiratory health. However, only limited studies are currently available on this topic in China. Objective To explore the association between exposure to pyrethroid insecticides and pulmonary function in children in Shanghai. Methods From August 2019 to January 2020, a cross-sectional study was conducted, recruiting 163 healthy school-aged children (aged 5–12 years) from Shanghai Children’s Hospital, Shanghai Jiao Tong University School of Medicine. Basic information, including age, height, weight, and family income, was collected. Urine samples from the children were collected and were analyzed for the levels of three pyrethroid insecticide metabolites: 3-phenoxybenzoic acid (3-PBA), cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (CDCCA), and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (TDCCA). Gas chromatography-tandem mass spectrometry (GC-MS/MS) was used for the analysis. Spirometry was used to assess pulmonary function and recorded following parameters: peak expiratory flow (PEF), forced expiratory flow between the 25th and 75th percentiles of forced vital capacity (FEF_25-75), forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), and FEV₁/FVC. Multiple linear regression and restricted cubic spline models were used to evaluate the associations between urinary pyrethroid insecticide metabolite levels and pulmonary function parameters. Results The study included 163 school-aged children, with an average age of (7.04 ± 2.08) years and an average body mass index (BMI) of (16.04 ± 2.72) kg·m⁻²; 75 (46.01%) of the participants were boys. The detection rates of 3-PBA, TDCCA, and CDCCA in urine were 85.28%, 17.79%, and 4.91%, respectively. The median creatinine-adjusted 3-PBA concentration was 0.150 μg·g⁻¹. After adjusting for confounders such as height, BMI, sex, age, delivery mode, annual family income, and maternal education level, the multiple linear regression model showed that urinary 3-PBA levels were negatively associated with both FVC [β=−0.030, 95% confidence interval (CI): −0.058, −0.003; P=0.031] and FEV₁ (β=−0.032, 95%CI: −0.064, 0.000; P=0.04998). The final restricted cubic spline model showed a nonlinear association between urinary 3-PBA levels and FVC, FEV₁, PEF, and FEF_25-75（P for nonlinear < 0.05；P for overall < 0.05）. Conclusion The level of pyrethroid insecticide exposure in school-aged children in Shanghai is relatively high. The urinary 3-PBA concentration is negatively associated with pulmonary function, indicating potential adverse effects of pyrethroid insecticide exposure on respiratory health of school-aged children.

Visual electrophysiology measurements have become a routine method of functional examination in ophthalmology. Small animal visual electrophysiology is an important tool for exploring the functionality of the visual system in small animals, finding widespread applications in neuroscience and drug research and development. This guide aims to offer a standardized operational guide for the operation of visual electrophysiological norms in small animals to ensure the accuracy and repeatability of the test. The study emphasizes different types of visual electrophysiological tests, such as electroretinogram(ERG)and visual evoked potential(VEP), evoked in small animals, and their application in different disease models. Detailed descriptions are provided regarding the selection and preparation of experimental animals, including the requirements of animal species, anesthesia methods and test environment. In terms of operational procedures, this guide highlights the correct electrode placement, the selection of stimulus parameters, and the key steps for signal acquisition and processing. According to different animal models, the corresponding operation suggestions were provided, and the troubleshooting methods of common problems were introduced. Beyond fundamental operations, this guide also focuses on the interpretation and reporting of test results. It explains various types of electrophysiological waveforms. In summary, this operational specification for small animal visual electrophysiology provides a comprehensive and detailed framework for researchers to ensure the standardization and reliability of tests. By following these guidelines, researchers can effectively utilize small animal visual electrophysiology techniques to gain insight into the function and abnormalities of the visual system.

Objective To investigate the changes in the prevalence of Babesia microti infections, spleen morphology and proportions of splenic immune cells in BALB/c mice following intravenous and intraperitoneal injections, so as to provide insights into unraveling the immune regulatory mechanisms of Babesia infections. Methods Laboratory - maintained B. microti strains were prepared into whole blood samples with 10% prevalence of B. microti infection. A total of 75 BALB/c mice were randomly divided into three groups, including the normal control group, intravenous injection group, and intraperitoneal injection group, of 25 mice in each group. Mice in the intravenous and intraperitoneal injection groups were administered 100 μL of whole blood samples with 10% prevalence of B. microti infection, with the day of injection recorded as d0, and animals in the normal control group were given no treatments. Blood was sampled from mice in each group via the tail tip on d7, d14, d21, d28 and d35, and prepared into thin-film blood smears, and B. microti infection was observed in red blood cells. Five mice were randomly sampled from each group and sacrificed on d7, d14, d21, d28 and d35, and spleen was collected for measurement of spleen size and weight. In addition, splenic cells were isolated, and the proportions of CD3e⁺ T cells, CD45R⁺ B cells, CD49b⁺ nature killer (NK) cells, and F4/80⁺ macrophages were detected in CD45⁺ lymphocytes using flow cytometry. Results The prevalence of B. microti infection in the intravenous (22.80%) and intraperitoneal injection groups (44.82%) peaked on d7 (χ² = 8.141, P < 0.01) and then rapidly decreased, and no parasites were observed on d35. The longest mouse spleen length [(32.91 ± 2.20) mm] and width [(9.82 ± 0.43) mm], and the greatest weight [(0.78 ± 0.10) g] were found on d14 in the intravenous injection group, and the longest spleen length [(32.42 ± 3.21) mm] and width [(10.25 ± 0.73) mm], and the greatest weight [(0.73 ± 0.09) g] were seen in the intra-peritoneal injection group on d21, d7 and d14, respectively. There were significant differences among the intravenous injection group, intraperitoneal injection group and the normal control group in terms of spleen length (F = 10.310, P < 0.05), width (F = 9.824, P < 0.05), and weight (F = 10.672, P < 0.05) on d21, and the mouse spleen length, width and weight were all significantly greater in the intraperitoneal injection group than in the intravenous injection group (allP values < 0.05). The proportions of splenic CD3e⁺ T cells [(60.60 ± 6.20)% and (39.68 ± 7.62)%], CD45R⁺ B cells [(43.32 ± 2.08)% and (49.53 ± 4.90)%], CD49b⁺ NK cells [(6.88 ± 1.34)% and (7.71 ± 1.59)%], and F4/80⁺ macrophages [(2.21 ± 0.29)% and (3.80 ± 0.35)%] peaked on d14, d21, d21 and d14 in the intravenous and intraperitoneal injection groups, respectively. There were significant differences in the proportions of CD3e⁺ T cells (F = 16.730, P < 0.05) and F4/80⁺ macrophages (F = 15.941, P < 0.05) among the intravenous injection group, intraperitoneal injection group and normal control group on d14, and a higher proportion of CD3e⁺ T cells and a lower proportion of F4/80⁺ macrophages were detected in the intravenous injection group than in the intraperitoneal injection group (both P values < 0.01). There were significant differences among the intravenous injection group, intraperitoneal injection group and normal control group on d21 in terms of proportions of splenic CD3e⁺ T cells (F = 9.252, P < 0.05), CD45R⁺ B cells (F = 14.349, P < 0.05), CD49b⁺ NK cells (F = 13.436,P < 0.05), and F4/80⁺ macrophages (F = 8.180, P < 0.05), and a higher proportion of CD3e⁺ T cells and lower proportions of CD45R⁺ B cells and F4/80⁺ macrophages were detected in the intravenous injection group than in the intraperitoneal injection group (all P values < 0.01). In addition, there was a significant difference in the proportion of CD3e⁺ T cells among the intravenous injection group, intraperitoneal injection group and normal control group on d28 (F = 9.772,P < 0.05), and a lower proportion of CD3e⁺ T cells was found in the intravenous injection group than in the intraperitoneal injection group (P < 0.01). Conclusions Both intraperitoneal and intravenous routes are effective to induce B. microti infections in BALB/c mice, and the prevalence of B. microti infections is higher in BALB/c mice through the intraperitoneal route than through the intravenous route. Intraperitoneal and intravenous injections with B. microti cause diverse spleen morphologies and proportions of splenic immune cells in mice, indicating routes of B. microti infections cause different impacts on immune response mechanisms in mice.