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 reveal the role of periodontal ligament stem cell-derived exosomes (PDLSC-Exos) in orthodontic bone remodeling, in order to provide new therapeutic strategies for orthodontic tooth movement (OTM). Methods : This study has been reviewed and approved by the Ethics Committee. Healthy periodontal ligament tissues from clinical orthodontic reduction extractions were collected, and periodontal ligament stem cells (PDLSCs) were isolated and cultured. When cultured to the third generation, their self-renewal ability and multidirectional differentiation potential were detected. PDLSC-Exos were isolated and purified by gradient centrifugation and identified by transmission electron microscopy, immunofluorescence, ZetaView, and nanoflow cytometry. The co-culture of 10 μg/mL PDLSC-Exos and PDLSCs (PDLSCs+Exos) induced osteogenic differentiation to evaluate the effect of osteogenesis. Bone marrow-mononuclear cells (BMMs), promoted by osteoclast differentiation [30 ng/mL macrophage colony stimulating factor (M-CSF) + 50 ng/mL receptor activator of nuclear factor-κ B ligand (RANKL)], and then were treated with 10 μg/mL PDLSC-Exos to assess the effect on osteoclasts. We established a rat model of OTM, and 50 μg/mL PDLSC-Exos was injected locally into the periodontal ligament before we established the model (OTM + Exos), every 2 days for 14 days. Alveolar bone remodeling was analyzed by micro-CT, and alveolar bone osteoclasts were analyzed by immunohistochemistry and immunofluorescence. Results: The isolated and purified PDLSCs met the basic characteristics of mesenchymal stem cells, and PDLSC-Exos had typical characteristics of extracellular vesicles. PDLSCs-Exos significantly promoted the osteogenic differentiation of PDLSCs, and promoted the osteoclast differentiation and bone resorption activity of BMMs (P < 0.05). The rate of alveolar bone remodeling in rats with local periodontal injection of PDLSC-Exos was significantly accelerated, and the tooth movement distance was significantly increased (P < 0.05); immunohistochemistry results showed that PDLSC-Exos promoted the differentiation of osteoclasts (P < 0.05). In addition, immunofluorescence showed that PDLSC-Exos co-localized with osteoclasts, indicating that PDLSC-Exos may promote osteoclast differentiation in vivo. Conclusion PDLSC-Exos accelerate the rate of orthodontic bone remodeling by promoting osteogenic differentiation of PDLSCs and osteoclast differentiation of BMMs, thereby accelerating OTM.

[Objective] To investigate the factors influencing the detection of HLA-C expression by flow cytometry. [Methods] A total of 12 hematopoietic stem cell suspension samples from peripheral hematopoietic stem cell volunteer donors were randomly collected after CD34⁺ cell counting detection. The influence of detecting different number of nucleated cell (500 000, 50 000 and 5 000), sequential order of red blood cell lysis and antibody incubation, and the HLA-C antibody with varied remaining time from the expiration date on the detection results of HLA-C expression by flow cytometry were investigated, respectively. The significance of differences between different groups was analyzed through Student t test. [Results] There was no significant difference in the proportion of HLA-C positive cells and mean fluorescence intensity (MFI) among the three groups with different nucleated cell numbers detected (500 000, 50 000 and 5 000) (P>0.05). The sequential order of red blood cell lysis and antibody incubation had no influence on the proportion of HLA-C positive cells (P>0.05), but HLA-C MFI value was significantly lower when antibody incubation was performed after red blood cell lysis than that when antibody incubation was performed before red blood cell lysis (P<0.05). The proportion of HLA-C positive cells and MFI value detected by HLA-C antibody remaining 24 months from the expiration date were significantly higher than those detected by HLA-C antibody remaining only 5 months from the expiration date (P<0.05). [Conclusion] The present study has investigated the factors of influencing HLA-C expression level by flow cytometry, the results have important reference and application value for standardizing the experimental operation of HLA-C expression and improving the accuracy and comparability of detection results.

ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang ［Yiqi Yangyin Jiedu prescription （YQYYJD）］ in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI）-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD （0， 2， 3， 4， 5， 6， 7， 8 g·L^-1） and cisplatin （0， 3， 6， 9， 12， 15， 18， 21， 24， 27 mg·L^-1） on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 （CCK-8） assay after 24 hours of intervention. The half-maximal inhibitory concentration （IC₅₀） for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group （complete medium）， YQYYJD group （5 g·L^-1）， cisplatin group （12 mg·L^-1）， and combined group （YQYYJD 5 g·L^-1 + cisplatin 12 mg·L^-1）. After 24 hours of intervention， cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay， and cell migration was evaluated by scratch and Transwell assays. Glucose consumption， lactate production， and adenosine triphosphate （ATP） levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins， including hexokinase 2 （HK2）， phosphofructokinase P （PFKP）， pyruvate kinase M2 （PKM2）， lactate dehydrogenase A （LDHA）， glucose transporter 1 （GLUT1）， and monocarboxylate transporter 4 （MCT4）， were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC₅₀ of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L^-1 and 12.91 mg·L^-1， respectively. In terms of cell proliferation， compared with the blank group， the cell survival rate and the number of colonies formed in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in cell survival rate and colony formation （P<0.01）. In terms of cell migration， compared with the blank group， the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane （P<0.01）. In terms of glycolysis， compared with the blank group， glucose consumption， lactate production， and ATP levels in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in glucose consumption， lactate production， and ATP levels （P<0.05）. Compared with the blank group， the protein expression levels of HK2， PFKP， PKM2， and LDHA in the YQYYJD， cisplatin， and combined groups were significantly decreased （P<0.01）. The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups （P<0.01）. No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes， including HK2， PFKP， PKM2， and LDHA， thereby inhibiting glycolysis.

AIM: To explore the control effects of wearing orthokeratology lens for 1 a on adolescent myopia patients with different diopters.METHODS: Prospective non-randomized controlled study. A total of 120 adolescent myopic patients(224 eyes), with an average age of 11.00±2.08 years old, who were fitted with orthokeratology lenses in the optometry department of our hospital from November 2022 to May 2023 were collected. There were 3 groups according to the spherical equivalent, including 86 eyes in the group of -0.50--2.00 D, 99 eyes in the group -2.25--4.00 D, and 39 eyes in group -4.25--6.00 D. Patients were followed up for 1 a to observe the changes of uncorrected visual acuity, axial length, corneal curvature, corneal central thickness and corneal endothelial cells density in the three groups after wearing lens for 1 a.RESULTS:A total of 113 cases(212 eyes)were followed up for 1 a, including 82 eyes in the group of -0.50--2.00 D, 95 eyes in the group of -2.25--4.00 D, and 35 eyes in the group of -4.25--6.00 D. There was no statistical difference in corneal central thickness and corneal endothelial cell density among the three groups of patients after wearing lens for 1 a(all P>0.05). Uncorrected visual acuity was significantly improved, and flat kerotometry(FK)and steep kerotometry(SK)were significantly flatter(both P<0.01). Furthermore, the growth of axial length in the three groups of patients after wearing lens for 1 a was 0.21±0.26, 0.13±0.21 and 0.09±0.10 mm, respectively(P<0.05). There were differences between the -0.50--2.00 D group and the -2.25--4.00 D group and -4.25--6.00 D group(P=0.028, 0.010), and there were no differences between the -2.25--4.00 D group and the -4.25--6.00 D group(P=0.344).CONCLUSION:It is safe and effective for young myopia patients to wear orthokeratology lenses, which can prevent the non-benign growth of the axial length and effectively delay the development of myopia, and the myopia control effect is better especially for myopia patients of above -2.0 D.

Gynecological malignancies pose a serious threat to women's health， and the early diagnosis and precise treatment are crucial for improving patients' prognosis. With the rapid advancement of Artificial Intelligence （AI） technology， it has become a revolutionary tool in the medical field. Through functions such as image recognition， data mining， and pattern recognition， it has opened up new avenues for the diagnosis and management of gynecological malignancies. This review comprehensively summarizes the latest research progress of AI in cervical cancer， ovarian cancer and endometrial cancer， with a special focus on its practical applications in tumor management involving early screening，diagnosis， treatment effect evaluation and prediction of prognosis，so as to provide guidance for the future research direction of AI in gynecological malignancies.

ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group （Saline） and hypertension group （Ang Ⅱ， which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps）， and supplemented daily with nicotinamide mononucleotide （300 mg/kg）， a precursor of NAD⁺. Blood pressure， endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA， SIRT3 and isocitrate dehydrogenase 2 （IDH2）. 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS， eNOS， SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure （P<0.001） and improved endothelial function and arterial stiffness （P<0.001） in hypertensive mice. In vitro， NMN improved endothelial function in AngII-stimulated endothelial cells （P<0.05） and attenuated mitochondrial oxidative stress levels （P<0.001）. Mechanistically， NMN elevated SIRT3 activity （P<0.001）， which subsequently enhanced IDH activity （P<0.001） and reduced oxidative stress levels in endothelial cells. Conversely， knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function （P<0.001）. ConclusionNAD⁺ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.

ObjectiveTo clearly identify the difference between rescue injuries and agonal injuries and to avoid duplicate identifications and misidentifications. MethodsBased on the forensic pathological data of 5 923 cases of death cause identification from 2013 to 2022 in Sun Yat-sen University Forensic Identification Center and Guangzhou Tianhe District Branch of Guangzhou Public Security Bureau， this study retrospectively studied the characteristics of rescue injuries and agonal injuries seen in cause of death identification and their influence on cause of death identification. ResultsAmong all the 5 923 cases， 640 cases were found to have rescue injuries or agonal injuries， and 624 cases received treatment， of which 609 cases were found to have rescue injuries （97.60%）， 44 cases were found to have agonal injuries， and 13 cases were found to have both types of injuries. Among the 640 cases， 441 were male and 199 were female. The age of death was discontinuously distributed from 0 to 95 years old. The leading cause of death was disease， followed by mechanical injury and asphyxia. The main manifestations of rescue injuries were rib and sternum fractures， soft tissue injuries in the prechest area or face， and pericardial rupture. The most common injuries in agonal stage were falling after unconsciousness， inhalation of foreign body in respiratory tract or multiple violent injuries. Among the 640 cases， 19 cases were repeatedly identified， including 15 cases of rescue injuries， 6 cases of agonal injuries， and 2 cases of both types of injuries. Compared with the cases where neither type of injuries was detected， the repeated identification rate of treatment injuries and agonal injuries was significantly increased （χ²=4.04， P=0.044； χ²=43.49， P<0.001）. Among the 640 cases， 11 cases （1.72%） were misidentified as the initial injuries in the first identification， and 13 cases had combined rescue injuries or agonal injuries that were involved in death. ConclusionsBy elucidating the epidemiological characteristics of the two types of injuries， this study proved that the two types of injuries were associated with higher rates of repeated identification and misidentification， which provided a reference for reducing repeated identification and misidentification and improving the accuracy of cause of death identification.

ObjectiveTo investigate the prevalence rate of chronic non-communicable diseases （NCDs） and the association with quality of life in middle-aged and elderly patients with HIV/AIDS. MethodsThis cross-sectional study surveyed 432 patients with HIV/AIDS （aged≥45 years） in the Infectious Disease Center in Guangzhou Eighth People’s Hospital of Guangzhou Medical University， and 366 participants were included in the analysis after quality control. A questionnaire and the EuroQol 5-Dimensional 3-level version （EQ-5D-3L） were used to investigate NCDs and quality of life and Tobit regression model was used to estimate the association between chronic diseases and quality of life. ResultsAmong the 366 participants， 29（7.9%） had cardiovascular disease， 45（12.3%） had hypertension， 122（33.3%） had hyperglycemia， 151（41.3%）had hyperlipidemia，7（1.9%） had cancer， 17 （4.6%） had chronic kidney disease， 38 （10.4%） had chronic liver disease， 21（5.7%） had musculoskeletal disorders， and 253（69.1%） suffered from at least one type of chronic diseases. The median （lower and upper quartiles） of EQ-5D utility index was 1.000（0.964~1.000）. Multivariate Tobit regression results of the total population showed that cancer ［b_a=-0.08，95%CI （-0.15，-0.01），P=0.036］， chronic kidney disease ［b_a=-0.07， 95%CI （-0.12，-0.02），P=0.006］， musculoskeletal disease ［b_a=-0.09， 95%CI （-0.13， -0.05），P<0.001］， and ≥3 types of chronic diseases［b_a=-0.05， 95%CI（-0.08，-0.01），P=0.013］ were negatively correlated with EQ-5D utility index. The stratified analysis results of different CD4+T cell levels showed that hypertension ［b_a=-0.07， 95%CI （-0.12， -0.02）， P=0.007］， chronic kidney disease ［b_a=-0.10，95%CI （-0.18，-0.03）， P=0.006］， musculoskeletal disease ［b_a=-0.15， 95%CI （-0.22，-0.07）， P<0.001］ and ≥3 types of chronic diseases ［b_a=-0.09， 95%CI （-0.09， -0.01）， P<0.001］ were negatively correlated with EQ-5D utility index in the group with CD4≤500 （cells/μL）， whereas cancer［b_a=-0.11， 95%CI （-0.20，-0.01）， P=0.031］ was negatively correlated with EQ-5D utility index in the group with CD4＞500（cells/μL）. ConclusionsThe prevalence rate of chronic non-communicable diseases in middle-aged and elderly patients with HIV/AIDS is relatively high. The classification of NCDs such as cancer or chronic kidney disease or other chronic diseases and the numbers of NCDs categories are negatively correlated with quality of life. However，this association varies among patients with HIV/AIDS of different CD4+T cell levels. It is suggested that we should try to prevent and identify NCDs at an early stage， strengthen linkages and integration of health services for AIDS and chronic NCDs， and jointly manage and control AIDS with chronic diseases to improve the quality of life among people living with HIV/AIDS.

Abstract In order to explore the pathogenesis of autism spectrum disorder (ASD) from a new perspective, it is found through literature review that vitamin D(Vit D) may play a significant role in the onset and development of ASD by inhibiting early brain overgrowth, regulating metabolism of central nervous system, modulating immune responses, reducing inflammation and influencing genome stability. Furthermore, Vit D supplementation in individuals with ASD has shown to alleviate symptoms. However, the mechanisms by which Vit D affects ASD remains unclear, and the effectiveness of Vit D treatment in improving ASD symptoms remains controversial due to variations in sample sizes, detection methods, dosage and confounding factors. Future research needs to focus on multi center, large scale randomized controlled trials and ASD animal models with Vit D deficiency to further explore the specific role of Vit D in the pathogenesis and treatment of ASD, which could provide reliable evidence for the early detection, intervention and treatment of ASD.