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 compare clinical effects of external fixation and minimally invasive percutaneous plate osteosynthesis (MIPPO) after external fixation in treating open fractures of tibial shaft. METHODS: From January 2020 to June 2022, 151 patients with open fracture of tibial shaft treated with external fixation stenting were divided into external fixation group and combined group according to different surgical methods. There were 81 patients in external fixation group, including 48 males and 33 females, aged from 21 to 68 years old with an average of (42.58±7.44) years old;according to Gustilo classification, 49 patients with typeⅡ, 32 patients with type ⅢA;the time from injury to treatment ranged from 2.5 to 10 h with an average of (4.25±0.74) h;external fixed stenting was performed. There were 70 patients in combined group, including 42 males and 28 females, aged from 20 to 69 years old with an average of (41.39±7.02) years old;35 patients with type Ⅱ and 35 patients with type ⅢA according to Gustilo classification;the time from injury to treatment ranged from 3 to 9 h with an average of (4.31±0.85) h;MIPPO treatment was performed after external fixed stenting. The time of callus formation, fracture healing and complications were compared between two groups. Rasmussen score and Hospital for Special Surgery (HSS) score were used to evaluate functional recovery of knee joint at 6 months after operation. RESULTS: Both groups were followed up for 6 to 13 months with an average of (10.17±2.33) months. The time of callus formation and fracture healing were (13.98±4.02) d and (70.26±12.15) d in combined group, and (18.56±4.37) d and (79.87±15.41) d in external fixation group, respectively. Combined group was better than external fixation group in the time of callus formation and fracture healing (P<0.05). At six months after operation, Rasmussen and HSS scores in combined group were (26.79±3.11) and (83.36±9.44), which were higher than those in external fixation group (24.51±4.63) and (79.63±8.46) (P<0.05). In external fixation group, there were 2 patients with incision infection, 2 patients with nail tract infection, 1 patient with stent loosening, fracture displacement, delayed union and malunion, and 1 patient with biocompatibility reaction in combined group, with statistical significance between two groups (P<0.05). CONCLUSION MIPPO could accelerate callus formation and fracture healing, improve knee function, improve clinical effects and reduce complications in patients with open tibial shaft fractures after external and external fixation.
Humans ; Male ; Female ; Middle Aged ; Adult ; Aged ; Tibial Fractures/physiopathology* ; Fracture Fixation, Internal/methods* ; Retrospective Studies ; Bone Plates ; External Fixators ; Fractures, Open/physiopathology* ; Stents ; Young Adult

ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

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.

Objective:To investigate the predictive value of elevated calprotectin S100A9 (S100A9) concentration during living-donor liver transplantation (LDLT) for early acute lung injury (ALI) in children with biliary atresia.Method:A retrospective analysis was conducted on 280 pediatric patients with biliary atresia who underwent LDLT using hyperreduced left lateral segment grafts at Tianjin First Central Hospital between January 2019 and January 2021. Based on intraoperative serum S100A9 levels at 30 minutes after graft reperfusion, patients were divided into the high S100A9 group (≥9.05 μg/L, 141 cases) and the low S100A9 group (<9.05 μg/L, 139 cases). General clinical characteristics were compared between the two groups. Univariate and multivariate logistic regression analyses were performed to examine the correlation between S100A9 levels and early postoperative ALI. The predictive value of risk factors was assessed using receiver operating characteristic (ROC) curve analysis with calculation of the area under the curve (AUC) .Result:A total of 280 eligible children were included in the study, with 141 in the high S100A9 group and 139 in the low S100A9 group. The incidence of ALI was significantly higher in the high S100A9 group (31.2%) compared to the low S100A9 group (10.8%). Multivariate regression analysis identified elevated preoperative creatinine levels ( OR=1.191, 95% CI: 1.069~1.321, P=0.002), increased intraoperative S100A9 concentrations ( OR=1.426, 95% CI: 1.272~1.599, P=0.021), and higher intraoperative blood transfusion volume ( OR=0.985, 95% CI: 0.973~0.997, P=0.017) as independent risk factors for postoperative ALI in pediatric LDLT. The predictive value of intraoperative S100A9 levels for ALI was significant, with an AUC of 0.816 (95% CI: 0.758~0.874), a sensitivity of 80.5%, a specificity of 73.7%, and an optimal cutoff value of 9.49 μg/L. Furthermore, preoperative albumin and creatinine levels were found to be correlated with increased intraoperative S100A9 levels. Conclusion:Elevated intraoperative S100A9 levels, increased preoperative creatinine levels, and higher intraoperative blood transfusion volumes are independent risk factors for early ALI following pediatric LDLT. S100A9 levels have strong predictive value for ALI occurrence, highlighting the need for perioperative monitoring and intervention strategies to improve postoperative outcomes.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

Objective:To investigate the predictive value of elevated calprotectin S100A9 (S100A9) concentration during living-donor liver transplantation (LDLT) for early acute lung injury (ALI) in children with biliary atresia.Method:A retrospective analysis was conducted on 280 pediatric patients with biliary atresia who underwent LDLT using hyperreduced left lateral segment grafts at Tianjin First Central Hospital between January 2019 and January 2021. Based on intraoperative serum S100A9 levels at 30 minutes after graft reperfusion, patients were divided into the high S100A9 group (≥9.05 μg/L, 141 cases) and the low S100A9 group (<9.05 μg/L, 139 cases). General clinical characteristics were compared between the two groups. Univariate and multivariate logistic regression analyses were performed to examine the correlation between S100A9 levels and early postoperative ALI. The predictive value of risk factors was assessed using receiver operating characteristic (ROC) curve analysis with calculation of the area under the curve (AUC) .Result:A total of 280 eligible children were included in the study, with 141 in the high S100A9 group and 139 in the low S100A9 group. The incidence of ALI was significantly higher in the high S100A9 group (31.2%) compared to the low S100A9 group (10.8%). Multivariate regression analysis identified elevated preoperative creatinine levels ( OR=1.191, 95% CI: 1.069~1.321, P=0.002), increased intraoperative S100A9 concentrations ( OR=1.426, 95% CI: 1.272~1.599, P=0.021), and higher intraoperative blood transfusion volume ( OR=0.985, 95% CI: 0.973~0.997, P=0.017) as independent risk factors for postoperative ALI in pediatric LDLT. The predictive value of intraoperative S100A9 levels for ALI was significant, with an AUC of 0.816 (95% CI: 0.758~0.874), a sensitivity of 80.5%, a specificity of 73.7%, and an optimal cutoff value of 9.49 μg/L. Furthermore, preoperative albumin and creatinine levels were found to be correlated with increased intraoperative S100A9 levels. Conclusion:Elevated intraoperative S100A9 levels, increased preoperative creatinine levels, and higher intraoperative blood transfusion volumes are independent risk factors for early ALI following pediatric LDLT. S100A9 levels have strong predictive value for ALI occurrence, highlighting the need for perioperative monitoring and intervention strategies to improve postoperative outcomes.

Neurodegenerative diseases are a type of disease characterized by specific types of neuronal loss and progressive progression,mainly represented by Alzheimer's disease and Parkinson's disease.This type of disease,due to its intractable and irreversible symptoms,brings great physical and psychological burden to patients,which is seriously disturbing their normal life.In terms of treatment,there is currently no specific treatment for Alzheimer's disease in clinical practice,and first-line treatment drugs for Parkinson's disease also have great limitations.In traditional Chinese medicine,kidney governs bone,generates marrow,and connects to the brain.In clinical evidence typing,premature aging,fatigue and forgetfulness,and tremor of limbs caused by kidney deficiency and medullary reduction are considered to be the main pathologies of these diseases.Di-Huang-Yin-Zi decoction which is derived from the"General Records of Holy Universal Relief",is recorded as a good formula for nourishing kidney yin and filling kidney yang.Clinical data shows that this formula has significant therapeutic effects in treating neurodegenerative diseases caused by kidney essence deficiency.Modern research results indicate that its mechanism of action involves inhibiting inflammatory reactions,regulating mitochondrial autophagy,reversing The hypothalamic-pituitary-adrenal axis abnormalities,and neuroprotection.The main effective ingredients in this formula include loganin,echinarin,and schisandrin A.This article aims to summarize and analyze the clinical efficacy,mechanism of action,and active ingredients of Di-Huang-Yin-Zi decoction in the treatment of Alzheimer's and Parkinson's disease in recent years,in order to clarify the research status of Di-Huang-Yin-Zi decoction in the neurodegenerative disease and provide reference for further research.