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 investigate the effects of jaceosidin on osteoarthritis （OA） of rats by regulating adenosine monophosphate-activated protein kinase （AMPK）/NOD-like receptor protein 3 （NLRP3） pathway. METHODS Rats were randomly separated into OA group， jaceosidin group （33.33 mg/kg）， AMPK inhibitor （Compound C， 20 mg/kg） group， jaceosidin （33.33 mg/kg）+Compound C （20 mg/kg） group， and sham operation group， with 12 rats in each group. Except for the sham operation group， the OA model was induced with modified Hulth method in all other groups. After successful modeling， they were given a relevant dose of jaceosidin or normal saline intragastrically， and Compound C or normal saline intraperitoneally， once a day， for consecutive 8 weeks. Twenty-four h after the last medication， the degree of knee joint swelling in rats from each group was measured. The pathological changes of the articular cartilage tissue in the knee joints， and the Mankin score were assessed. The levels of tumor necrosis factor-α （TNF-α）， interleukin-18 （IL-18）， and IL-6， as well as the protein expressions of collagen Ⅱ， aggrecan （ACAN）， and a disintegrin and metalloproteinase with thrombospondin 5 （ADAMTS5）， phosphorylated AMPK （p-AMPK）， AMPK， NLRP3， cleaved-caspase-1， and cleaved-IL-1β were detected in the articular cartilage tissue of rats’ knees. RESULTS Compared with OA group， the cartilage tissue defect of jaceosidin group was relieved， the cartilage matrix staining was deepened， and the number of chondrocytes was increased. Knee swelling， Mankin score， the levels of TNF- α， IL-18 and IL-6， and protein expressions of ADAMTS5， NLRP3， cleaved-caspase-1 and cleaved-IL-1β in knee cartilage were significantly decreased or down-regulated. Protein expressions of collagen Ⅱ， ACAN and phosphorylation level of AMPK were significantly increased or up-regulated （P＜0.05）. Compound C significantly reversed the improvement effects of jaceosidin on the above indexes of OA rats （P＜0.05）. CONCLUSIONS Jaceosidin may inhibit inflammation and extracellular matrix degradation in OA rats by regulating the AMPK/NLRP3 signaling pathway.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Objective To investigate the influence of auricular acupressure combined with repetitive transcranial magnetic stimulation(rTMS)on swallowing function and neurological function in stroke pa-tients.Methods A total of 120 patients with dysphagia after stroke admitted to the hospital from January 2022 to June 2023 were selected as the research objects and divided into the control group,the auricular acu-pressure group,the rTMS group and the combined group according to the random number table method,with 30 cases in each group.The control group received routine care,the auricular acupressure group received auric-ular acupressure treatment on the basis of the control group,while the rTMS group received rTMS treatment,and the combined group received both auricular acupressure and rTMS treatment.All interventions lasted 4 weeks.Swallowing function was assessed before and after treatment using Functional Oral Intake Scale(FOIS),modified Mann Assessment of Swallowing Ability(MASA),and Water Swallow Test.Swallowing-related quality of life was evaluated before and after treatment by the Swallowing Quality of Life(SWAL-QOL)questionnaire.Neurological impairment was assessed before and after treatment using National Institu-tes of Health Stroke Scale(NIHSS).Results After treatment,FOIS and MASA scores in the four groups were higher than those before treatment,with the auricular acupressure group and the rTMS group showing higher scores than the control group,and the combination group significantly higher than the other three groups(P<0.05).The overall effectiveness rate for swallowing function in the combination group was 93.33%,significantly higher than 60.00%in the control group,63.33%in the auricular acupressure group,and 73.33%in the rTMS group(P<0.05),while there was no significant difference among the other three groups(P>0.05).After treatment,SWAL-QOL scores in the four groups were higher than that before treat-ment,with the auricular acupressure group and the rTMS group showing higher scores than the control group,and the combination group significantly higher than the other three groups(P<0.05).After treat-ment,NIHSS scores in the four groups were lower than that before treatment,and the combination group had significantly lower scores compared to the other three groups(P<0.05).Conclusion Auricular acupressure combined with rTMS could improve swallowing function and quality of life,and promote neurological function recovery in stroke patients.

Objective To explore the mechanism of action of lamotrigine in the treatment of major depressive disorder(MDD).Methods Information on the drug targets of lamotrigine and the therapeutic targets of MDD were collected for intersection target gene analysis and protein-protein interaction screening.Various biological pathways related to lamotrigine in treatment of MDD were determined through gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.The screened core targets were preliminarily validated using molecular docking technology.Further validation of Mendelian randomization was conducted using genome-wide association analysis data from gamma-aminobutyric acid recep tor-associated protein-like 1(GABARAPL1)and MDD in the OpenGWAS database.Results The biological pathways related to lamotrigine in treatment of MDD were identified,which included gamma-aminobutyric acid(GABA)ergic synapses,nicotine addiction,glutamatergic synapses,endogenous cannabinoid signaling.Molecular docking showed that the docking energy of lamotrigine with GABRA1,GABRB2,GABRA6,GABRD,GABRG2,GABRG1,GABRA5,GABRA4,GABRB3,and GABRA2 receptors was-5.8 kCal·mol-1.Among them,the GABRB3 receptor showed the strongest docking energy with lamotrigine,which was-9.5 kCal·mol-1.In the genome-wide association analysis data of GABARAPL1,303 single nucleotide polymorphisms were associated with GABARAPL1(P＜5 × 106).15 single nucleotide polymorphisms were screened and retained for Mendelian randomization analysis,and the results showed that GABA receptors may be an important therapeutic target for MDD.Conclusion The treatment of MDD with lamotrigine may be achieved by acting on GABA receptors,which provided a research basis for the clinical application of lamotrigine in treating MDD.

Objective To elucidate utilization patterns,cost and safety of Bruton's tyrosine kinase inhibitors(BTKi)in the real world.Methods A retrospective cohort was designed and constructed using real-world BTKi data from a single lymphoma center.Descriptive analysis was performed to describe the demographic and clinical characteristics of the population.Medicine utilization and cost were quantified by defined daily doses(DDDs)and defined daily dose cost(DDDc),respectively.A generalized estimating equation(GEE)was used to explore the potential influencing factors of platelet aggregation rate(PAR).Results The study cohort included 193 patients[median age,65 years;77(39.90％)women],most of whom received ibrutinib(n=109,56.48％),and 77.20％patients combined BTKi with chemotherapy or targeted therapy.The implementation of national negotiation policy had a large impact on medicine utilization and cost.The DDDs difference between the two BTKis was reduced from 18.55 to 1.41 times.The DDDc for ibrutinib decreased from 1 619.99 Yuan to 567.00 Yuan,and that for zanubrutinib from 706.25 Yuan to 340.00 Yuan was already lower than ibrutinib.Interruptions were more readily observed in patients treated with ibrutinib,and hematological toxicity was the main adverse drug event(ADE)leading to treatment interruption.Besides,the GEE model showed that combining BTKi with antiplatelet medication significantly decreases the PAR[β=-34.35％,95％confidence interval(CI):-41.60％--27.11％,P＜0.001].Compared to zanubrutinib,ibrutinib also notably reduces the PAR(β=-12.38％,95％CI:-24.50％--0.27％,P＜0.05).Conclusion After the implementation of national negotiation policy,there is no significant difference in the clinical preference for two BTKis.Compared with ibrutinib,zanubrutinib showed an advantage in terms of economic profile,treatment interruptions caused by ADE,and the effect on PAR.