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 whether interleukin-37(IL-37)affects macrophage M1 polarization via nu-cleotide oligomerization of structural domain receptor protein 1(NOD1)/nuclear factor κB(NF-κB)in plasma cell mastitis.Methods A total of 15 patients with plasma cell mastitis were recruited according to the collection standard as inflammatory breast tissue and normal breast tissue with a distance of ≥ 3 cm from the edge of the in-flammatory breast tissue.QPCR was performed to detect NOD1 and IL-3.Phorbol ester(PE)was used to induce THP-1 cells to differentiate into resting macrophages(M0).Lipopolysaccharide(LPS)combined with interferon(IFN-γ)was used to induce the polarization of M0 macrophages towards the M1 phenotype.NOD1 lentiviral RNA interference or over-expression vectors were constructed to regulate the expression of NOD1 in M1 macrophages.M0 macrophages were pretreated with IL-37 recombinant protein and then incubated with LPS and IFN-γ for induction.The expression of NOD1,IL-37,M1 markers(IL-6 and iNOS)and M2 markers(IL-10 and Arg-1)was quantified by qPCR.Western blot was employed to assess the protein level of NOD1,NF-κB p65,and p-NF-κB p65.Co-immunoprecipitation was used to detect the interaction between NOD1 and IL-37.Results Up-regulation of NOD1 and down-regulation of IL-37 as were found in inflammatory breast tissues(P＜0.05).Compared to M0 cells,M1 cells showed up-regulated NOD1 and M1 markers and the elevated phosphorylated NF-κB p65 but the down-regulated IL-37(P＜0.05).In M1 macrophages,both NF-κB inhibitor and NOD1 knockdown led to the down-regulation of NOD1 and M1 markers and caused a decrease in the phosphorylated NF-κB p65(P＜0.05).IL-37 recombinant protein decreased phosphorylation of NOD1,M1 marker and NF-κB p65,which was reversed by over-expression of NOD1.IL-37 may interact with NOD1(P＜0.05).Conclusions IL-37 may inhibit M1 polarization in macrophages by down-regulating NOD1/NF-κB pathway thereby preventing plasma cell mastitis progression.

Objective:To investigate the related factors of cognitive impairment in middle-aged and old-aged patients with type 2 diabetes mellitus(T2DM).Methods:A total of 970 patients with T2DM(585 middle-aged group and 385 old-aged group)were selected from residents of a large community in Beijing from September to December 2018.The Mini-Mental State Examination(MMSE)was used to assess the cognitive func-tion.Multivariate logistic regression was used to analyze the related factors.Results:The detection rates of cognitive impairment were 12.0％and 13.5％in middle-aged and old-aged patients with T2DM,respectively.Among mid-dle-aged patients with T2DM,work(OR=0.22,95％CI:0.03-0.77)and education at the junior college or un-dergraduate level and above(OR=0.18,95％CI:0.04-0.55)were protective factors for cognitive impair-ment.Myocardial infarction(OR=4.13,95％CI:1.26-13.63)was a risk factor for cognitive impairment.Among old-aged patients with T2DM,drinking tea 1-2 times a week(OR=0.11,95％CI:0.01-0.58)and education at the junior college or undergraduate level and above(OR=0.19,95％CI:0.05-0.54)were protective factors for cognitive impairment.Stroke(OR=3.64,95％CI:1.55-8.39)and good sleep self-assessment(OR=2.75,95％CI:1.13-7.35)were risk factors for cognitive impairment.Conclusion:Cognitive impairment in middle-aged pa-tients with T2DM is related to work,education level and myocardial infarction,and cognitive impairment in old-aged patients with T2DM is related to lifestyle,education level and stroke.

Objective:To investigate the related factors of cognitive impairment in middle-aged and old-aged patients with type 2 diabetes mellitus(T2DM).Methods:A total of 970 patients with T2DM(585 middle-aged group and 385 old-aged group)were selected from residents of a large community in Beijing from September to December 2018.The Mini-Mental State Examination(MMSE)was used to assess the cognitive func-tion.Multivariate logistic regression was used to analyze the related factors.Results:The detection rates of cognitive impairment were 12.0％and 13.5％in middle-aged and old-aged patients with T2DM,respectively.Among mid-dle-aged patients with T2DM,work(OR=0.22,95％CI:0.03-0.77)and education at the junior college or un-dergraduate level and above(OR=0.18,95％CI:0.04-0.55)were protective factors for cognitive impair-ment.Myocardial infarction(OR=4.13,95％CI:1.26-13.63)was a risk factor for cognitive impairment.Among old-aged patients with T2DM,drinking tea 1-2 times a week(OR=0.11,95％CI:0.01-0.58)and education at the junior college or undergraduate level and above(OR=0.19,95％CI:0.05-0.54)were protective factors for cognitive impairment.Stroke(OR=3.64,95％CI:1.55-8.39)and good sleep self-assessment(OR=2.75,95％CI:1.13-7.35)were risk factors for cognitive impairment.Conclusion:Cognitive impairment in middle-aged pa-tients with T2DM is related to work,education level and myocardial infarction,and cognitive impairment in old-aged patients with T2DM is related to lifestyle,education level and stroke.

Objective:To study and screen the differential expression of inflammatory proteins in diabetes skin ulcers and common skin ulcers, so as to provide experimental basis for further research on anti-inflammatory and healing drug targets of diabetes skin ulcers.Methods:The tissues of 11 patients with diabetes skin ulcer, 12 patients with common skin ulcer and 11 patients with normal skin were collected from the First Hospital of Hunan University of Chinese Medicine. The levels of inflammatory protein Toll like receptor 4 (TLR4), nuclear factor κB (NF-κB), pro-inflammatory factor interferon -γ (IFN -γ), tumor necrosis factor - α (TNF -α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1β (IL-1β), macrophage chemotactic protein-1 (MCP-1), anti-inflammatory factors epidermal growth factor (EGF), interleukin-4 (IL-4), and interleukin-10 (IL-10) were detected in three groups of tissues using enzyme-linked immunosorbent assay (ELISA).Results:Compared with normal tissues, the concentrations of TLR4, NF-κB, IFN -γ, TNF -α, IL-1β, IL-6, IL-8, MCP-1 and EGF in common ulcer skin tissues and diabetes ulcer tissues were higher, and the concentrations of IL-10 were lower, with statistically significant differences (all P<0.05); Compared with the normal tissue, the concentration of IL-4 in diabetes ulcer tissue was lower, the difference was statistically significant ( P<0.05); Compared with ordinary ulcer skin tissue, the concentrations of TLR4, NF-κB and MCP-1 in diabetes ulcer tissue were higher, and the concentrations of IL-4 were lower, with statistically significant differences (all P<0.05). Conclusions:The skin ulcer in diabetes patients will have inflammatory reaction, and high glucose promotes the inflammatory reaction of skin ulcer, which may be related to the abnormal expression of TLR4, NF-κB, MCP-1 and IL-4. TLR4/NF-κB signal pathway and inflammatory factors MCP-1 and IL-4 may be the target of the inflammation regulation of diabetes skin ulcer.

Objective To explore the expression of microRNA(miR)-100-5p in thyroid cancer cells and its regulatory effects on cell proliferation and apoptosis through experiments.Methods The relative expressions of miR-100-5p in thyroid cancer cell lines(TPC-1 and KTC-1)and normal thyroid cell lines(Nthy ori3-1)were detected using fluorescence quantitative PCR.After transfection of miR-100-5p mimic,miR-100-5p inhibitor,and corresponding negative controls(miR-mimic NC,miR-inhibitor NC)into TPC-1 cells,the proliferation condition of TPC-1 cells was detected using CCK-8,and the apoptosis condition of TPC-1 cells was detected using flow cytometry.Prediction and functional enrichment analysis of target genes of miR-100-5p were performed using the miRTarBase and TargetScan7.2 databases.The targeted regulatory effect of miR-100-5p on fibroblast growth factor receptor 3(FGFR3)was validated using Western blot and dual luciferase reporter gene experiments.Results Compared with Nthy-ori3-1 cells,the expression levels of miR-100-5p in TPC-1 cells(1.87±0.03 vs 1.00±0.03)and KTC-1 cells(6.33±0.47 vs 1.00±0.03)were both up-regulated,with significant differences(t=-34.220,-19.588,all P＜0.05).The 450nm absorbance(A450nm)of cells transfected with miR-100-5p mimic at 24,48 and 72 h were higher than the miR-mimic NC group,with significant differences(t=-7.516,-17.828,-8.445,all P＜0.05).Conversely,the A450nm values of cells transfected with miR-100-5p inhibitor at 24,48 and 72 h were lower than the miR-inhibitor NC group,with significant differences(t=6.720,6.782,6.073,all P＜0.05).The apoptosis rate after transfection with miR-100-5p mimic was decreased compared to miR-mimic NC group(7.43％±0.49％vs 10.55％±0.80％),with significant differences(t=5.767,P=0.004).Compared to miR-inhibitor NC group,the apoptosis rate after transfection with miR-100-5p inhibitor was increased(3.19％±0.22％vs 2.64％±0.15％),with significant differences(t=-3.606,P=0.023).Western blot experiments showed that FGFR3 protein expression levels in the miR-100-5p mimic group were down-regulated compared to the miR-mimic NC group(0.78±0.12 vs 1.00±0.00),with significant differences(t=3.071,P=0.037).Compared to the miR-inhibitor NC group,FGFR3 protein expression levels in the miR-100-5p inhibitor group were up-regulated(1.17±0.07 vs 1.00±0.00),with significant differences(t=-4.509,P=0.046).There was no significant difference in the luciferase activity of the FGFR3 wild-type(1.01±0.17 vs 1.00±0.00)and mutant groups(0.99±0.11 vs 1.00±0.00)between miR-100-5p mimic and miR-mimic NC,and the differences were statistically significant(f=-0.057,0.181,P=0.96,0.873).Conclusion MiR-100-5p in thyroid cancer cells was up-regulated,which may promote cell proliferation and inhibit apoptosis.It may become a new biomarker and regulatory target in the diagnosis and treatment of thyroid cancer.

Objective:To analyze the perioperative clinical characteristics of patients with oral cancer underwent radical resection and flap reconstrution and the nursing managements.Methods:From January 2020 to December 2020, 658 patients with oral cancer underwent radical resection and flap reconstrution in the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University were retrospectively analyzed. All patients were divided into the elderly group (≥60 years) and the younger group (< 60 years), including 279 cases in the elderly group and 379 cases in the younger group. The perioperative clinical data of the patients were collected, and the perioperative general situation, postoperative complications and influencing factors of complications were analyzed.Results:There were differences between the two groups in the aspects of sex ( χ2 = 12.38, P<0.001), preoperative BMI ( t = 2.43, P = 0.015), smoking history ( χ2 = 18.34, P<0.001), preoperative anesthesia grade ( χ2 = 25.61, P = 0.001), preoperative coexisting disease ( χ2 = 46.97, P<0.001), whether oral floor or tongue cancer ( χ2 = 16.68, P<0.001), whether free flap ( χ2 = 6.81, P = 0.003), operation time ( t = 2.19, P = 0.029), preoperative test index hemoglobin ( t = 4.96, P<0.001), albumin ( t = 5.44, P<0.001), D-dimer( Z = -13.52, P<0.001), calcium levels ( t = 4.07, P<0.001) and postoperative complications ( χ2 = 14.55, P<0.001). Multivariate analysis of postoperative complications showed that the age ( OR = 1.021, 95% CI = 1.005-1.037, P = 0.011), preoperative D-dimer ( OR = 1.219, 95% CI = 1.026-1.447, P = 0.024) and the preoperative coexisting disease ( OR = 1.642, 95% CI = 1.108-2.432, P = 0.013) were the risk factors for the postoperative complications. Multivariate analysis of discharge with tube showed that the age ( OR = 1.017, 95% CI = 1.003-1.031, P = 0.017), preoperative BMI ( OR = 0.917, 95% CI = 0.873-0.963, P = 0.001), whether oral floor or tongue cancer ( OR = 2.135, 95% CI = 1.475-3.091, P<0.001), and operation time ( OR = 1.220, 95% CI = 1.120-1.328, P<0.001) were the related factors for the discharge with tube. Conclusion:In view of the above risk factors, it is beneficial for the physical and mental recovery of patients to pay attention to preoperative evaluation, make adequate preoperative preparation, postoperative nursing and observation, improve swallowing function training, prepare for discharge, pay attention to continuous nursing, and establish a tertiary hospital-community-family rehabilitation system.

Objective:To investigate the clinical effect of free fibula flap transplantation in repairing the defect of mandibular osteoradionecrosis (ORN).Methods:A total of 151 mandibular ORN patients undergoing free fibular flap transplantation were selected from August 2005 to September 2020 in the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Among them, 109 patients were males and 42 patients were females, aged (54.1±10.1) (ranged 31-85) years old. The clinical data of the patients was collected and the survival rate of the flaps and postoperative function were calculated to evaluate the surgical efficacy. The χ 2 test was used for difference analysis. Results:Among the 151 patients, mandibular ORN caused by radiotherapy for nasopharyngeal carcinoma accounted for 79.5% (120/151). The average time for mandibular ORN appeared was 5(6) years after radiotherapy. Facial artery [57.2%(87/152)] and superior thyroid artery [32.9%(50/152)] were the main anastomotic arteries in the recipient area. There was no significant difference in the necrosis rates of the two flaps [10.3%(9/87) and 12.5% (5/50), respectively, P=0.949]. The main anastomotic veins in the recipient area were the external jugular vein [48.4%(135/279)] and the common facial vein [26.5%(74/279)]. Twenty-five cases (16.6%) had one vein anastomosed, and 126 cases (83.44%) had two veins anastomosed. There was no significant difference in the flap necrosis rate between the two conditions [20.0%(5/25) and 7.1%(9/126), respectively, P=0.100]. Ninety-seven cases (64.2%) used the peroneal musculocutaneous-fascia composite flap to repair the maxillofacial soft and hard tissue defects. Thirteen cases (8.6%) underwent the restorations with digital virtual surgery design, of which 5 cases were repaired with dental implants at the same time. After the operations, lower respiratory tract infection occurred in 17 patients (11.3%), and upper respiratory tract obstruction occurred in 3 cases (2.0%). The survival rate of the flap after operation was 90.7% (136/151), and 21 patients (13.9%) had flap vascular crisis. Delayed healing of maxillofacial wounds occurred in 33 cases (21.9%). After 3 to 24 months of follow-ups, 110 patients (76.9%) had no fistula inside/outside the oral cavity, 118 patients (82.5%) had an improvement in opening mouth of increasing (≥0.5 cm) after surgery, 135 patients (94.4%) had pain relief, 97 cases (67.8%) could eat normal diet, semi-liquid or soft food, and 137 cases (95.8%) were satisfied or basically satisfied with the treatment effects. Conclusions:The free fibular flap transplantation is an effective method to repair mandibular ORN defects. Preoperative vascular assessment is helpful for the selection of recipient vessels. Facial artery, superior thyroid artery, external jugular vein and common facial vein can be used as the main recipient vessels. The repair of the peroneal musculocutaneous-fascia composite flap facilitates the closure of internal and external fistulas. Digital technology can help to restore the maxillofacial shape more accurately, improve the patient′s occlusal and chewing function and enhance the quality of life of mandibular ORN patients.

Starting from participating the high-level professional competition, our school has built a talent training system with the spirit of "biomaker" and an innovative practical ability training system. Such system takes the interest of student as the starting point, and relies on the strong scientific research and teaching infrastructure. The programme gives full play to students' initiatives and enhances the scientific research literacy and comprehensive ability of undergraduates majoring in biotechnology. It is an effective exploration of the traditional university education model and meets the urgent demand for innovative talents training in the era of rapid development of life sciences.
Biological Science Disciplines ; Biotechnology ; Genetic Engineering ; Humans ; Students ; Universities

Objective:To observe the changes of abdominal aortic calcification and biochemical indicators after parathyroidectomy (PTX) in the maintenance hemodialysis (MHD) patients with secondary hyperparathyroidism (SHPT).Methods:The MHD patients with SHPT who were followed up for 2 years were analyzed retrospectively and divided into PTX surgery group ( n=26) and non-surgery group ( n=18) according to whether they underwent PTX, and then the abdominal aortic calcification score (AACS), intact parathyroid hormone (iPTH), blood calcium and phosphorus after 2 years were observed in the two groups. The PTX surgery group was divided into advanced group and non-advanced group according to whether abdominal aortic calcification had progressed or not 2 years after the operation. Indicators such as age, dialysis age, iPTH, blood calcium, blood phosphorus, calcium and phosphorus product were compared between the two groups to analyze the possible factors related to the development of abdominal aortic calcification. Results:A total of 44 patients meeting the inclusion criteria were included, with 26 in the PTX surgery group and 18 in the non-surgery group. The baseline data of the PTX surgery group and the non-surgery group showed statistical difference in the age of dialysis ( P<0.05), but no statistical differences in gender, age and history of hypertension. Compared with preoperative indicators, postoperative iPTH, blood calcium and phosphorus significantly reduced (all P<0.05), and there was no significant difference in AACS. There were 8 cases (30.77%) of accelerating progress of calcification, 8 cases (30.77%) of improvement in calcification, 10 cases (38.46%) of calcification stability. After 2 years, iPTH value of non-advanced group was significantly lower than advanced group [(20.62±6.44) ng/L vs (132.72±76.83) ng/L], while the preoperative AACS progress was higher in non-advanced group [(13.11±2.71) vs (2.00±1.41)] (all P<0.05). In non-surgery group, AACS was significantly higher after 2 years [(10.44±1.65) vs (8.05±1.26)], blood phosphorus and the product of blood calcium and phosphorus significantly decreased (all P<0.05) , and the levels of iPTH and blood calcium did not significantly change. Pearson correlation analysis showed that the decreased value between preoperative AACS and 2-year postoperative AACS was positively correlated with the decreased value of iPTH ( r=0.534, P=0.012), blood calcium ( r=0.643, P=0.004), blood phosphorus ( r=0.897, P<0.001) and calcium-phosphorus product ( r=0.568, P=0.021) , and negatively correlated with preoperative AACS ( r=-0.647, P=0.014). Conclusions:Small sample data shows that PTX can correct parathyroid hormone, calcium and phosphorus for long term, and prevent abdominal aortic calcification progression, even reverse vascular calcification. Whether abdominal aortic calcification improves or not may be associated with the decrease of iPTH, calcium, phosphorus and the product of blood calcium and phosphorus.