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 effect of Shenmai injection on the preservation quality of suspended red blood cells of high hemoglobin population in Xizang plateau. [Methods] Whole blood (400 mL, n=8) collected by the Xizang Autonomous Region Blood Center was centrifuged at 3 000 g for 10 minutes to remove most of the plasma, followed by the addition of 100 mL of MAP preservation solution to obtain plateau suspended red blood cells, which were then divided into three equal portions. One portion was the control group, and another part had 15 mL of MAP preservation solution added, which was the dosage group. The third portion involved diluting Shenmai injection with MAP, followed by addition of 15 mL of MAP preservation solution containing Shenmai to the red blood cells, resulting in a final concentration of Shenmai injection of 1%, which was the Shenmai group. Blood routine, pH value, electrolytes, glucose, lactate, free Hb, adenosine triphosphate (ATP), P50, phosphatidylserine (PS) and other indicators were detected at day 1, 21 and 35, respectively. [Results] The Hb concentration and Hct of the dosage group and the Shenmai group were significantly lower than those of the control group, with values of (179.3±17.8) vs (181.0±17.1) vs (199.1±19.5) g/L for Hb concentration and (53.2±2.6)% vs (53.3±2.5)% vs (58.4±3.1)% for Hct. The three groups maintained this pattern until the end of storage. In the middle and late stages of preservation, the glucose and Na⁺ contents in the dosage group and the Shenmai group were higher than those in the control group, while the lactate and K⁺ contents were lower than those in the control group. At the end of storage, the glucose and Na⁺ content of the Shenmai group was higher than that of the dosage group, while the lactate and K⁺ content were lower than that of the dosage group. From day 1 to day 35 of storage, the hemolysis rate of the Shenmai group was significantly lower than that of the control group and the dosage group. On day 21 and 35 of storage, the PS expression rate in the Shenmai group was significantly lower than that in the control group and the dosage group, which were (6.52±0.40)% vs (7.24±0.91)% vs (8.27±0.93)% and (7.29±0.53)% vs (9.37±0.82)% vs (8.39±0.76)%, respectively. [Conclusion] The hemolysis rate and PS of suspended red blood cells of Xizang high altitude prepared by adding Shenmai injection were significantly lower than those in the control group and the dosage group, which was conducive to reducing hemolysis and slowing down the aging of red blood cells, and had a certain improvement on the preservation quality of suspended red blood cells in Xizang plateau people.

[Objective] To use Chitosan Methacryloyl (CSMA) loaded with artificial platelet-derived exosomes (aPexos) as the needle body material, and gelatin and carboxymethyl chitosan (CMCS) loaded with Epigallocatechin gallate(EGCG) as the backing material to prepare microneedles, aims to investigate the therapeutic effect and mechanism of aPexos-EGCG microneedles in the treatment of burn wound healing. [Methods] First, aPexos were extracted using ultrasound and gradient ultracentrifugation. The concentration, morphology, and growth factor content (TGF-β1, PDGF-BB, VEGF) of the exosomes were assessed using NTA, transmission electron microscopy, and ELISA kits. The aPexos and EGCG were then dissolved in the needle body and backing materials, respectively. The aPexos and EGCG were loaded into the needle body and backing layer, respectively. The morphology, mechanical properties, and puncture performance of the microneedles were examined, and the preparation conditions for the microneedles loaded with aPexos-EGCG were optimized. Finally, animal experiments and tissue staining were conducted to assess the efficacy of the aPexos-EGCG microneedles in promoting burn wound healing in rats. [Results] The size distribution of aPexos was mainly in the range of 50-150 nm, with an average diameter of 132.7±3.8 nm and an average concentration of approximately 2.88×10¹³±3.62×10¹² particles/mL. The concentrations of TGF-β1, PDGF-BB, and VEGF were approximately 1 363±135.9 ng/mL, 63.5±14.8 ng/mL, and 1 606.0±77.5 pg/mL, respectively. Mechanical property testing of the microneedles indicated that, compared with the blank microneedles, the drug-loaded microneedles had sufficient piercing ability to penetrate the stratum corneum of the skin. The results of the rat burn wound healing experiment showed that the wound healing rates of the d 3, d 7, aPexos-EGCG microneedle group compared to the control group showed significant differences, with respective values of (47.64±12.5)% vs (18.11±6.40)%, (87.45±5.57)% vs (79.85±5.03)%(P<0.05). Hematoxylin-eosin (HE) staining revealed more intact epidermal layers in the aPexos-EGCG microneedle group. Masson staining showed that the collagen deposition percentage in the aPexos-EGCG microneedle group was higher than in the control group. Immunofluorescence staining results indicated that the aPexos-EGCG microneedle group had a reduced content of M1-type macrophages and an increased content of M2-type macrophages. Additionally, the vascular markers CD31 and α-SMA showed elevated expression in this group, with significant differences compared to the other groups (P<0.05). [Conclusion] The aPexos-EGCG microneedle developed in this study exhibits good mechanical properties, capable of successfully penetrating the skin's stratum corneum and delivering aPexos and EGCG. aPexos promotes wound repair, while EGCG regulates the ratio of M1 and M2 macrophages at the wound site and suppresses the inflammatory response. This microneedle can effectively promote wound healing in rats with burn injuries, offering a novel approach for tissue repair.

Objective: To prepare platelet membrane biomimetic liposomes loaded with vincristine sulfate (VCR) for targeted delivery to tumor. Methods: Vincristine sulfate liposomes (LIPO) were prepared using the pH-gradient method, followed by the fusion of platelet membranes and subsequent drug loading to obtain platelet membrane biomimetic liposomes (PLM-LIPO). The particle size, polydispersity index (PDI), Zeta potential, and drug encapsulation efficiency (EE%) of both liposomes were characterized. The tumor-targeting capability was evaluated through in vitro cellular experiments and in vivo biodistribution studies. Results: The optimal preparation conditions for LIPO were determined as follows: DPPC-to-cholesterol molar ratio of 1∶1, internal aqueous phase of 0.3 M pH 4.0 citrate buffer, external aqueous phase of 1 M Na HPO solution, drug-to-lipid ratio of 1∶10, drug loading temperature of 60℃, and loading time of 10 minutes. The LIPO exhibited a mean particle size of (147.3±2.24) nm, PDI of 0.078±0.014, Zeta potential of (-3.54±0.75) mV, and EE% of 91.37±0.47. For PLM-LIPO, prepared via membrane fusion followed by drug loading, the mean particle size was (185.3±3.61) nm, PDI was 0.075±0.022, Zeta potential was (-18.91±1.54) mV, and EE% was 63.36±2.45. In the CD62P validation experiment, the fluorescence intensity of PLM-LIPO was five times higher than that of LIPO. In vitro cellular uptake experiments revealed that PLM-LIPO showed 1.3-fold and 1.2-fold higher uptake rates compared to LIPO at 6 h and 12 h, respectively. In vivo experiments demonstrated that 1h after administration, the accumulation of PLM-LIPO at tumor sites was 4-fold higher than that of LIPO and 6-7 times higher than that in healthy mice. Conclusion: The platelet membrane biomimetic liposomes loaded with vincristine sulfate were successfully developed. Both cellular uptake and tissue distribution studies confirmed the PLM-LIPO enhanced tumor-targeting capability.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

ObjectiveTo explore the relationship between self-assessed health and age-adjusted Charlson comorbidity index （AICC） in older adults， and to further analyze the differences in this relationship across gender groups. MethodsBased on the China health and retirement longitudinal study （CHARLS） database， this study selected data on basic characteristics， chronic disease status， depressive symptoms， and self-assessed health of older adults aged ≥60 years. Chi-square tests were used to perform a preliminary analysis of the association between these factors and AICC scores. A multifactorial ordered logistic regression model was constructed to assess the effects of each influencing factor on AICC， while multiple linear regression analysis was used to explore the linear relationship between self-rated health and AICC scores. Additionally. Stratified analysis by gender was performed to evaluate gender differences. ResultsA total of 10 911 participants were included， with a mean age of 67.40±5.94 years； 6 249 （57.3%） were male and 4 662（42.7%） were female. The distribution of AICC scores was categorized into low-risk， moderate-risk， higher-risk， and high-risk groups， accounting for 23.5%， 50.2%， 20.6%， and 5.7%， respectively. Multifactorial logistic regression analysis revealed that self-rated health was negatively associated with AICC in the total population and in the male geriatric group （OR=0.843， 95% CI： 0.776， 0.917， P=0.001）， （OR=0.886， 95% CI： 0.796 ， 0.987， P=0.028）， but did not reach statistical significance in the female geriatric group . Linear regression analysis further indicated a significant negative linear relationship between self-rated health and AICC （b=-0.485， 95% CI： -0.516，-0.455， P＜0.001）.This relationship was consistent in both male （b=-0.356， 95% CI： -0.406，-0.305， P＜0.001） and female （b=-0.373， 95% CI： -0.435，-0.310， P＜0.001） subgroups， with a stronger negative association in females. ConclusionSelf-rated health is significantly negatively associated with AICC， and attention should be given to self-rated health in the female geriatric population. Self-rated health can serve as an important tool for identifying elderly group at high risk of comorbidities providing a valuable basis for precise intervention.

A high-performance liquid chromatography method using pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate was developed to determine the content of 15 amino acids in the medicinal snakes Bungarus Parvus, Agkistrodon, and Zaocys. The results showed that the total amino acid(TAA) content ranged from 277.13 to 515.05 mg·g~(-1), with the top four amino acids in all three species being glutamic acid(Glu), glycine(Gly), aspartic acid(Asp), and lysine(Lys). The essential amino acid(EAA) content ranged from 74.56 to 203.94 mg·g~(-1), with Agkistrodon exhibiting the highest content. The non-essential amino acid(NEAA), semi-essential amino acid(semi-EAA), and medicinal amino acid(MAA) content ranged from 189.06 to 318.23, 12.89 to 33.53, and 179.83 to 342.33 mg·g~(-1), respectively, with Zaocys having the highest content in these categories. Amino acid nutritional value was evaluated using the amino acid ratio(RAA), amino acid ratio coefficient(RCAA), and amino acid ratio coefficient score(SRCAA), and the results indicated that all three medicinal snakes possessed good nutritional value. The amino acid composition was similar across the species, though significant differences in content were observed. Based on these differences, an orthogonal partial least squares-discriminant analysis(OPLS-DA) model was established, which could clearly distinguish between the three medicinal snake species. The key differences in amino acid content included Gly, tyrosine(Tyr), Glu, and serine(Ser), which may be related to the observed clinical application differences among the species. Further research into the mechanisms of these differential amino acids is expected to provide more insights into the clinical application disparities of these three medicinal snake species.
Amino Acids/chemistry* ; Animals ; Nutritive Value ; Chromatography, High Pressure Liquid ; Snakes/classification* ; Bungarus

OBJECTIVE: To explore clinical characteristics, lesion sites and correlation differences of different types of diabetic foot gangrene, and to provide evidence-based basis for clinical classification of diabetic foot gangrene. METHODS: A retrospective analysis was conducted on 266 patients with newly diagnosed diabetic foot gangrene who were admitted from January 2018 to December 2018, including 183 males and 83 females, aged from 35 to 92 years old with an average of (69.55±10.84) years old, and they were divided into wet gangrene group and dry gangrene group according to the different natures of gangrene. There were 139 patients in wet gangrene group, including 98 males and 41 females, aged from 35 to 90 years old with an average of (68.95±10.93) years old. There were 127 patients in dry gangrene group, including 85 males and 42 females, aged from 38 to 92 years old with an average of (70.21±10.75) years old. Body mass index (BMI), waist-to-hip ratio (WHR), body temperature, skin temperature difference between the affected and healthy sides of the lower extremities, and Wagner grade between two groups were recorded to evaluate symptoms and signs. The white blood cell count (WBC), neutrophil percentage (NEUT%), and C-reactive protein (C-reactive protein), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and interleukin-6 (IL-6) in peripheral blood between two groups were detected and compared to evaluate the infection status;the severity of diabetic peripheral neuropathy (DPN) was evaluated by using Toronto Clinical Scoring System (TCSS);the degree of pain in patients with diabetic foot gangrene was evaluated by numerical rating scale (NRS); ankle-brachial index (ABI) and popliteal artery blood flow velocity were used to evaluate the degree of arterial lesions. Spearman correlation analysis was used to analyze the correlations between gangrene TCSS, ABI and age, BMI, WHR, body temperature, calf skin temperature difference, WBC, NEUT%, CRP, ESR, PCT, IL-6, NRS, and Wagner classification indicators. RESULTS: The body temperature, skin temperature difference between the affected and healthy sides of the lower extremities, Wagner grade, WBC, NEUT%, CRP, ESR, PCT, IL-6, TCSS score, ABI, and popliteal artery blood flow velocity in wet gangrene group were higher than those in dry gangrene group (P<0.01), and BMI, WHR, and NRS score in dry gangrene group were higher than those in wet gangrene group;the differences were all statistically significant (P<0.01). The results of Spearman correlation analysis showed TCSS score of gangrene patients was correlated with body temperature (r=0.214), calf skin temperature difference (r=0.364), WBC (r=0.240), NEUT% (r=0.291), CRP (r=0.347), ESR (r=0.167), PCT (r=0.241), IL-6 (r=0.316), and popliteal fossa arterial blood flow velocity (r=0.261) and Wagner grade (r=0.273) were positively correlated, and the differences were statistically significant (P<0.01). ABI was negatively correlated with age (r=-0.183), BMI (r=-0.252), WHR (r=-0.288), and NRS score (r=-0.354), and the differences were statistically significant (P<0.01). CONCLUSION Diabetic foot gangrene is an extremely difficult and critical disease. Wet gangrene has a significant synergic effect with infection and neuropathy, while dry gangrene is closely related to vascular occlusion. The main contradiction of gangrene could be revealed through blood vessels, nerves and infection, providing evidence-based basis for the selection of debridement timing, anti-infection strategies and revascularization, with the aim of reducing the risk of amputation.
Humans ; Male ; Female ; Aged ; Middle Aged ; Diabetic Foot/diagnosis* ; Aged, 80 and over ; Adult ; Retrospective Studies ; Gangrene/physiopathology* ; C-Reactive Protein