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.

BackgroundPatients with chronic schizophrenia often suffer from cognitive impairment. Traditional cognitive rehabilitation training has problems such as a single form and poor compliance， making it urgent to develop new cognitive intervention methods. ObjectiveTo explore the intervention effect of smartphone games on the cognitive function of patients with chronic schizophrenia， and to analyze the differences in cognitive function improvement between patients of different genders， in order to provide references for the cognitive function intervention of these patients. MethodsThis study was a prospective cohort study. A total of 30 patients who were hospitalized in the Psychiatry Department of Chaohu Hospital Affiliated to Anhui Medical University from March to October 2021， met the diagnostic criteria for schizophrenia as defined in the International Classification of Diseases， tenth edition （ICD-10）， and had a disease duration of above 5 years， were selected as the research subjects. All patients received smartphone game intervention for 12 weeks， 5 times a week， each session lasting 1 hour， in addition to conventional antipsychotic drug treatment. At the baseline and at 3， 6， 9， and 12 weeks of the intervention， the cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status （RBANS）， the Positive and Negative Syndrome Scale （PANSS） was used to assess mental symptoms， and the Problematic Mobile Gaming Questionnaire （PMGQ） was used to assess addiction symptoms. ResultsA total of 26 patients （86.67%） completed the study， including 13 females and 13 males. The time effects， group effects， and interaction effect between time and group for the immediate memory factor score of RBANS in the female group and the male group were all statistically significant （F=36.682， 5.712， 3.090， P<0.05 or 0.01）， and the time effects and group effects for the verbal and delayed memory factors as well as the total score in both groups were also statistically significant （F=3.841， 6.149， 15.372， P<0.05 or 0.01）. The time effects and group effects of the total score of PANSS in both groups had no statistical significance （F=2.041， 0.623， P>0.05 for both）， and the interaction effect between time and group was statistically significant （F=5.728， P<0.01）. The time effects， group effects， and interaction effect of the total score of PMGQ in both groups were all without statistical significance （F=2.672， 0.166， 0.642， P>0.05 for both）. ConclusionSmartphone game intervention may help improve the cognitive function of patients with chronic schizophrenia （especially immediate memory， verbal function， and delayed memory）， and the benefits are greater for female patients. The smartphone game intervention did not induce game addiction， but no significant improvement in psychotic symptoms was observed. ［Funded by Excellent Young Talents Support Program of Anhui Provincial Department of Education （number， gxyqZD2022022）； www.chictr.org.cn number， ChiCTR2100044113］

BACKGROUND:Studies have shown that rheumatoid arthritis and osteoporosis are positively correlated,but the causal relationship and related mechanisms have not yet been confirmed.With the cross-fertilization of computer science and life sciences,Mendelian randomization and bioinformatics analyses based on genome-wide association study(GWAS)and transcriptome sequencing data can assess the causal relationship between two diseases,explore the related mechanisms,and mine the therapeutic targets,which will be beneficial to the precision treatment of rheumatoid arthritis combined with osteoporosis.OBJECTIVE:To explore the causal relationship between rheumatoid arthritis and osteoporosis using two-sample Mendelian randomization and to mine potential co-morbid targets and potential targeted drugs through summary-data-based Mendelian randomization and bioinformatics analyses,aiming to provide theoretical basis for mechanism exploration and precision treatment in the field of rheumatoid arthritis combined with osteoporosis.METHODS:(1)Firstly,GWAS data of rheumatoid arthritis,osteoporosis,and cis-expression quantitative trait locus(cis-eQTL)in Asian and European populations were downloaded from the GWAS Catalog,IEU Open GWAS,FinnGen,and eQTLGen databases,and were used for two-sample Mendelian randomization analysis and summary-data-based Mendelian randomization analysis.(2)Transcriptome sequencing data of rheumatoid arthritis(GSE93272 and GSE15573)were downloaded from the GEO database for bioinformatics analysis.(3)Subsequently,forward and inverse Mendelian randomization analyses between rheumatoid arthritis and osteoporosis were performed,and inverse variance weighted was used as the main metric for the analyses,and the results were corroborated with MR Egger,simple mode,weighted median and weighted mode.(4)Then,the genes closely related to rheumatoid arthritis and osteoporosis were identified based on the summary-data-based Mendelian randomization analysis,and the co-disease targets of rheumatoid arthritis and osteoporosis were mined based on cross-analysis.Meanwhile,the biological functions of the co-morbid targets were verified based on bioinformatics analysis and cellular experiments.(5)In addition,a rheumatoid arthritis risk prediction nomogram was constructed based on DYRK2,and its prediction performance was verified by receiver operating characteristic curve,correction curve and decision curve.Finally,the target potential drugs were mined based on Enrichr database and molecular docking was performed.RESULTS AND CONCLUSION:(1)Forward Mendelian randomization analysis of rheumatoid arthritis and osteoporosis showed statistically significant results except for GCST90044540 and GCST90086118,and all other results indicated a significant causal relationship and positive correlation between rheumatoid arthritis and osteoporosis.(2)Inverse Mendelian randomization analysis suggested that no significant causal relationship was seen between osteoporosis and rheumatoid arthritis.(3)Summary-data-based Mendelian randomization analysis identified a total of 412 and 344 genes positively associated with rheumatoid arthritis and osteoporosis,and 421 and 347 genes negatively associated.Based on the cross-analysis,26 co-morbid genes were subsequently obtained.Among them,DYRK2 was a potential therapeutic target,and subsequent bioinformatics analysis and cellular experiments confirmed its important role in the progression of rheumatoid arthritis and osteoporosis.(4)Furthermore,the constructed nomogram has excellent predictive performance.Finally,four potential DYRK2-targeting drugs(undecanoic acid,metyrapone,JNJ-38877605,and ACA)were discovered and molecular docking also demonstrated reliable targeting ability.(5)In conclusion,based on GWAS data from Asian and European populations,we successfully demonstrated that rheumatoid arthritis and osteoporosis are causally related at the genetic level,DYRK2 is a potential therapeutic target,and four small molecules are potential target drugs.

Objective: To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs. Materials and Methods: This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20–40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation participants with ultrasound-detected ULs (diameter ≥3 cm), without IHC analysis, and 3) prospective diagnostic test accuracy was evaluated in consecutive participants with ultrasound-detected ULs (diameter ≥3 cm;age, 20–40 years), using IHC for 2-SC for determining the FH status and subsequent genetic testing in those with positive 2-SC results to identify whether FH mutations were germline or somatic in origin. The choline and fumarate peaks in MRS were classified as positive, negative, or technical failure (TF). TFs were analyzed separately and excluded from the primary diagnostic accuracy calculations. T1-, T2-, and diffusion-weighted images were interpreted as hyperintense or hypointense. The enhancement rate and apparent diffusion coefficient were also acquired. Diagnostic performance was compared between MRS and various magnetic resonance imaging (MRI) features. Results: The optimal MRS parameters for the fumarate peak were echo time (TE) = 140 ms and an average of 256. Among the 360 prospective participants, 37 were confirmed to have FH-dULs. MRS showed positive fumarate peaks in 35 of 37 FH-dULs.After excluding six TFs, the positive fumarate peak on MRS showed 94.6% (35/37) sensitivity, 99.7% (316/317) specificity, and 99.2% (351/354) accuracy, all of which were significantly superior to those of other MRI features (P ≤ 0.002). Conclusion A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.

BACKGROUND:Studies have shown that rheumatoid arthritis and osteoporosis are positively correlated,but the causal relationship and related mechanisms have not yet been confirmed.With the cross-fertilization of computer science and life sciences,Mendelian randomization and bioinformatics analyses based on genome-wide association study(GWAS)and transcriptome sequencing data can assess the causal relationship between two diseases,explore the related mechanisms,and mine the therapeutic targets,which will be beneficial to the precision treatment of rheumatoid arthritis combined with osteoporosis.OBJECTIVE:To explore the causal relationship between rheumatoid arthritis and osteoporosis using two-sample Mendelian randomization and to mine potential co-morbid targets and potential targeted drugs through summary-data-based Mendelian randomization and bioinformatics analyses,aiming to provide theoretical basis for mechanism exploration and precision treatment in the field of rheumatoid arthritis combined with osteoporosis.METHODS:(1)Firstly,GWAS data of rheumatoid arthritis,osteoporosis,and cis-expression quantitative trait locus(cis-eQTL)in Asian and European populations were downloaded from the GWAS Catalog,IEU Open GWAS,FinnGen,and eQTLGen databases,and were used for two-sample Mendelian randomization analysis and summary-data-based Mendelian randomization analysis.(2)Transcriptome sequencing data of rheumatoid arthritis(GSE93272 and GSE15573)were downloaded from the GEO database for bioinformatics analysis.(3)Subsequently,forward and inverse Mendelian randomization analyses between rheumatoid arthritis and osteoporosis were performed,and inverse variance weighted was used as the main metric for the analyses,and the results were corroborated with MR Egger,simple mode,weighted median and weighted mode.(4)Then,the genes closely related to rheumatoid arthritis and osteoporosis were identified based on the summary-data-based Mendelian randomization analysis,and the co-disease targets of rheumatoid arthritis and osteoporosis were mined based on cross-analysis.Meanwhile,the biological functions of the co-morbid targets were verified based on bioinformatics analysis and cellular experiments.(5)In addition,a rheumatoid arthritis risk prediction nomogram was constructed based on DYRK2,and its prediction performance was verified by receiver operating characteristic curve,correction curve and decision curve.Finally,the target potential drugs were mined based on Enrichr database and molecular docking was performed.RESULTS AND CONCLUSION:(1)Forward Mendelian randomization analysis of rheumatoid arthritis and osteoporosis showed statistically significant results except for GCST90044540 and GCST90086118,and all other results indicated a significant causal relationship and positive correlation between rheumatoid arthritis and osteoporosis.(2)Inverse Mendelian randomization analysis suggested that no significant causal relationship was seen between osteoporosis and rheumatoid arthritis.(3)Summary-data-based Mendelian randomization analysis identified a total of 412 and 344 genes positively associated with rheumatoid arthritis and osteoporosis,and 421 and 347 genes negatively associated.Based on the cross-analysis,26 co-morbid genes were subsequently obtained.Among them,DYRK2 was a potential therapeutic target,and subsequent bioinformatics analysis and cellular experiments confirmed its important role in the progression of rheumatoid arthritis and osteoporosis.(4)Furthermore,the constructed nomogram has excellent predictive performance.Finally,four potential DYRK2-targeting drugs(undecanoic acid,metyrapone,JNJ-38877605,and ACA)were discovered and molecular docking also demonstrated reliable targeting ability.(5)In conclusion,based on GWAS data from Asian and European populations,we successfully demonstrated that rheumatoid arthritis and osteoporosis are causally related at the genetic level,DYRK2 is a potential therapeutic target,and four small molecules are potential target drugs.

ObjectiveTo investigate the effect of Sanet Vision Integrator (SVI)-based visuomotor integration training on the severity of neglect symptoms, upper limb motor function and activities of daily living (ADL) in patients with post-stroke unilateral spatial neglect (USN). MethodsFrom July, 2023 to September, 2025, 41 patients with post-stroke USN in Beijing Bo'ai Hospital were enrolled and randomly assigned to control group (n = 20) and experimental group (n = 21). Both groups received conventional rehabilitation and visual scanning training, while the experimental group received supplementary SVI-based visuomotor integration training, including saccadic, rotation and hand-eye coordination training, for eight weeks. They were assessed with Chinese Behavioral Inattention Test-Hong Kong version (CBIT-HK), Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and modified Barthel Index (MBI) before and after treatment. ResultsAfter treatment, all the scores significantly improved in both groups (|t| > 4.004, P < 0.001), and the total scores of CBIT-HK and the core visual search sub-items (star cancellation, line crossing and letter cancellation), FMA-UE and MBI were better in the experimental group than in the control group (t > 2.096, P < 0.05). ConclusionSVI-based visuomotor training can effectively alleviate the USN symptoms, broaden the span of visual attention, facilitate the functional recovery of the affected upper extremity, and improve ADL in patients after stroke.

As an innovative dosage form, traditional Chinese medicine(TCM) dry powder inhalers have emerged as a focal point in the research and development of new preparations due to its high efficiency, safety, and bioavailability. This paper systematically reviewed the relevant literature and patents associated with TCM dry powder inhalers to analyze the origins and the current research and development status. Furthermore, this paper probed into the research and development ideas of TCM dry powder inhalers regarding clinical positioning, prescription screening, and druggability. Additionally, the paper thoroughly analyzed the technical barriers in druggability studies and elaborated on corresponding research techniques and coping measures. Furthermore, it emphasized the need for improved regulations and policies governing TCM dry powder inhalers, advocated for strengthened oversight, and called for the establishment of a scientific quality evaluation system. Measures such as promoting production-education-research collaboration, enhancing personnel training, and fostering international exchanges were proposed to provide a scientific and systematic reference for the future research, development, and application of TCM dry powder inhalers, thereby facilitating the rapid modernization of TCM.
Humans ; Dry Powder Inhalers/trends* ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/instrumentation* ; Administration, Inhalation

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

Peyronie's disease (PD) is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages. In this study, we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD: transforming growth factor-β1 (TGF-β1), fibrin, sodium tetradecyl sulfate (STS) combined with TGF-β1, and polidocanol (POL) combined with TGF-β1. The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature. The STS + TGF-β1 combination resulted in both histological and morphological alterations, but with a high incidence of localized necrosis that led to animal death. The POL + TGF-β1 combination produced pathological changes and curvature comparable to STS + TGF-β1 and led to fewer complications. In conclusion, fibrin, STS + TGF-β1, and POL + TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats. The POL + TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.
Animals ; Male ; Penile Induration/drug therapy* ; Rats ; Transforming Growth Factor beta1/metabolism* ; Disease Models, Animal ; Fibrin ; Penis/drug effects* ; Polidocanol/administration & dosage* ; Rats, Sprague-Dawley ; Polyethylene Glycols/administration & dosage* ; Injections