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 value of proteinuria in evaluating the severity of pre-eclampsia (PE) and assessing the maternal and neonatal outcomes of PE.Methods:The clinical records of 265 pregnant women who were diagnosed with PE at Peking Union Medical College Hospital from January 2011 to June 2021 were retrospectively analyzed. According to 24-hour urine protein (24-hUPro) results, pregnant women were divided into two groups: the non-proteinuric group (24-hUPro<0.3 g, n=10) and proteinuric group (24-hUPro≥0.3 g, n=255). The proteinuric group was further divided into 3 subgroups based on proteinuria levels: mild group (0.3 g≤24-hUPro<2.0 g, n=119), moderate group (2.0 g≤24-hUPro<5.0 g, n=59), and severe group (24-hUPro≥5.0 g, n=77). The demographic and clinical data, laboratory indicators, pregnancy complications, maternal and neonatal outcomes were compared between different groups. Results:In proteinuric subgroups, increased proteinuria was associated with earlier onset gestations, higher incidence of headache, peripheral tissue edema, serosal effusion, intrauterine growth restriction, and abnormal umbilical cord blood flow (all P<0.05). There were no significant differences in the incidence of placental abruption, eclampsia and maternal mortality among the three subgroups, but there were significant differences in the incidence of neonatal birth weight and multiple neonatal complications (all P<0.05). Compared with the proteinuric group, the non-proteinuric group showed later onset gestation (median:34.7 vs 37.6 weeks) and gestational age of delivery (median:36.0 vs 38.4 weeks), lower proportion of ocular vascular lesions [56.7% (135/238) vs 2/9], higher birth weight (median: 2 325 vs 2 750 g), and lower rate of neonatal intensive care unit occupancy [54.3%(127/234) vs 1/10;all P<0.05]. Conclusions:The proteinuria plays an important role in assessing the severity of PE and maternal and neonatal outcomes, but it is not the only indicator. The non-proteinuric PE pregnant women might still lead to severe maternal and neonatal outcomes.

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.

Objective:To study the application value of different operation methods in the treatment of left hepatolithiasis in special position (the stone is located in the sagittal section of left portal vein and/or near the proximal end of left hepatic vein).Methods:From July 2015 to June 2018, 58 patients with left hepatolithiasis in special position in Department of General Surgery, the First People′s Hospital of Tianmen City of Hubei Province were analyzed retrospectively. According to the different operation methods, they were divided into two groups: left liver excision under laparoscopy and gallbladder incision stone group (left liver excision group, n=28) and laparoscopic left-half liver excision and bile tube excision stone removal group (left half liver excision group, n=30). The operation time, intraoperative bleeding, postopera-tive hospital stay, postoperative biliary fistula, postoperative bleeding, postoperative stone residue and stone recurrence were compared between the two groups.The measurement data with normal distributions were represented as ( Mean± SD), and comparison between groups was done using the t test. The chi-square test and Fisher precision test were used for comparison between counting data. Results:All 58 patients underwent laparoscopic surgery. Left liver excision group surgery time, in-serum bleeding, number of days hospitalized after surgery, number of postoperative bile fistula cases, number of postoperative bleeding cases were (161.53±30.56) min, (203.45±26.69) mL, (9.26±3.3. 86) days, 1 case, 1 case, left half liver excision group (153.16±42.63) min, (198.79±30.82) mL, (9.59±4.01) days 1 case, 1 case, The difference between the two groups was not statistically significant ( P>0.05). The number of postoperative stone residues was more than that of the left liver and outer leaf excision group (4 cases) than that of the left half of the liver excision group (1 case), and the number of postoperative stone recurrence cases was more than that of the latter (1 case), all of which were statistically significant ( P<0.05). The number of stone residues and stone recurrences after left liver excision group was 4 and 5 cases respectively, and the left half liver excision nurses were 1 case and 1 case, respectively, and the difference between the two was statistically significant ( P<0.05). Conclusion:For the left hepatolithiasis in special position (the stone is located in the sagittal section of the left branch of the portal vein and (or near the proximal end of the left hepatic vein in imaging), the lower abdominal left hemihepatectomy + choledocholithotomy is a safer and more effective treatment.

Objective: To investigate the clinical characteristics of salivary gland tumors and their pathological types. Methods: Data from 2 456 patients with salivary gland tumors diagnosed between January 1973 and December 2018 at Sun Yat-sen Memorial Hospital of Sun Yat-sen University were collected, and their gender, age and tumor pathological type, location, and benign and malignant composition ratios were retrospectively analyzed. Results: Over the 46-year study period, 2 456 patients with salivary gland tumors were treated; 41.9% were female, and 58.1% were male. The peak incidence was found among the 40 to 60 years of age group, in which 593 (24.1%) patients had malignant tumors and 1 863 (75.9%) had benign tumors. The ratio of benign and malignant tumors was 3.1∶1. The top two most common benign tumors were pleomorphic adenoma (58.7%) and Warthin tumors (33.6%). The top two most common malignant tumors were mucoepidermoid carcinoma (27.7%) and adenoid cystic carcinoma (26.1%). The most common sites of benign pleomorphic adenomas were the parotid glands, palate, and submandibular glands. Mucinous epidermoid carcinomas in malignant tumors were common in the parotid glands and small salivary glands. The incidence of salivary gland tumors in this group has increased each year, and this group accounted for 53.3% of the total cases over the past 10 years. Conclusion The number of patients with salivary gland tumors is increasing each year. The total incidence of salivary gland tumors is higher in men than in women. Large salivary gland tumors are mainly benign tumors, and small salivary gland tumors are more common. Polymorphic adenomas, Warthin tumors, and mucoepidermoid carcinomas are the most common tumor types; patients 40~60 years old are most likely to have benign salivary glands and have a high incidence of malignant tumors.

Objective:To explore the effects of different doses of Ethephon on testes of male pups.Methods:Thirty-two 45-day-old healthy female Sprague-Dawley (SD) rats were randomly divided into the control group and the low dose, middle dose and high dose Ethephon groups by the random figure table.The female rats in the low dose, middle dose and high dose Ethephon groups were given 200, 400, and 800 mg/kg Ethephon solution, respectively.The control group was treated with 9 g/L saline.After the birth of the offspring, the mother rats were not administrated with any medications, and the male offspring rats were given Ethephon solution instead.Twelve offspring male rats were randomly selected from each group and killed at the age of 0, 14 and 28 days after birth.Fresh testicular tissues were stained with hematoxylin eosin (HE), and the morphological changes of testicular tissues were observed under light microscope.The apoptotic cells were labeled by terminal dexynucleotidyl transferase (TdT) mediated dUTP nick end labeling (TUNEL) method and the apoptosis index (AI) of spermatogenic cells was detected by fluorescence microscope.Results:(1) Compared with the newborn rats in the middle dose group, low dose group and control group, se-miniferous tubules in the newborn rats of the high dose group were slightly thicker, and seminiferous cells were arranged slightly in disorder.The AI of the newborn rats in high dose group was significantly higher than that in the control group (1.00±0.06 vs.0.41±0.03, P<0.01). The AI of the newborn rats in the middle dose group was not significantly different from that in the control group and the low dose group ( P>0.05). (2) The seminiferous tubules of the 14-day-old rats in the low dose, middle dose and high dose Ethephon groups were significantly thicker and arranged more loosely than those in the control group.Compared with the control group, there were very few seminiferous cells, which were arranged disorderly in the low dose, middle dose and high dose Ethephon groups.The AI of the 14-day-old rats in the low dose, middle dose and high dose Ethephon groups was (2.13±0.10), (2.18±0.10) and (3.90±0.23), respectively, which were significantly higher than that in the control group (1.00±0.02) ( F=2 508.36, P<0.01). There was no significant difference in the AI between the middle dose and low dose groups ( P>0.05). (3) Compared with the control group, the seminiferous tubules of the 28-day-old rats in the low dose, middle dose and high dose groups were significantly thicker and arranged much more loosely, and spermatogenic cells were even less and arranged in a severely disordered way.The AI of 28-day-old rats in the low dose group (5.52±0.13), the middle dose group (9.44±0.07) and the high dose group (14.56±0.27) was significantly higher than that in the control group (3.11±0.13) ( F=10 784.69, P<0.01). Conclusions:Ethephon can thicken the seminiferous tubules of newborn and young rats, cause the germ cells to arrange disorderly, promote the apoptosis of spermatogenic cells and reduce the ability of spermatogenesis.Moreover, a longer exposure of the rats to a higher concentration of Ethephon will result in more serious damage to testicular tissues.

Objective To evaluate the correlation between microvascular invasion(MVI) and prognosis in patients with hepatocellular carcinoma (HCC),and to analyse the influencing factors of MVI in patients with HCC.Methods Total of 81 patients with hepatocellular carcinoma treated in Beijing Hospital from January 2014 to December 2016 were retrospectively studied.There were 65 males and 16 females.The mean age was 59.6± 12.7 years,and the age ranged from 21 to 87 years old.Pathological examination showed presence of MVI in 35 patients.Results Total of seventy-six patients with hepatocellular carcinoma were followed-up.The 1-,2-,3-and 4-year overall survival rates in the 35 patients with microvascular invasion of hepatocellular carcinoma were 78.6％,55.4％,38.3％,and 32.2％,respectively.The 1-,2-,3-,and 4-year overall survival rates of the 41 patients without microvascular invasion were 93.4％,76.5％,68.2％ and 68.2％,respectively.The difference was significant (P＜0.05).Cox multivariate regression analysis showed that microvascular invasion was an independent risk factor of overall survival after surgery (HR=3.071,95％ CI:1.239～7.610,P＜0.05).Sub-group analysis was done on patients with microvascular invasion based on pathological results which included the number of MVI lesions,the call number in the MVI lesion,the distance of the MVI to the primary liver cancer,and the gradings of MVI.There were no significant differences in the overall survival outcomes (P＞0.05).Multivariate logistic regression analysis showed the maximum diameter of tumor ＞ 5 cm (OR =6.340,95％ CI:2.000 ～ 20.096),preoperative total bilirubin (TBil) ＞ 17 μmol/L (OR =5.067,95％CI:1.386 ～ 18.525),and preoperative alpha-fetoprotein (AFP) ＞400 μg/L (OR =6.042,95％ CI:1.435 ～ 25.444) were independent risk factors of microvascular invasion (P＜ 0.05).Conclusion Hepatocellular carcinoma patients with microvascular invasion had poor prognosis.Preoperative AFP,preoperative TBil,and diameter of tumor were independent risk factors of microvascular invasion in patients with hepatocellular carcinoma.

Objective : To analyze the value of virtual surgical planning in the surgical treatment of osteoradionecrosis of the mandible and to provide a reference for clinical practice. .Methods : From September 2017 to June 2018, 13 patients with mandibular osteoradionecrosis were evaluated preoperatively using the 3D virtual surgery software CMF Proplan 2.0. The surgical guide was designed and 3D printed. Bone resection, fibula shaping and bone graft localization were completed during the operation. In some cases, implants were implanted at the same time, and denture restoration was completed 3 to 6 months after surgery. Patients’ general information, perioperative data, and efficacy evaluation were analyzed. Results: All patients underwent surgery successfully. The survival rate of the free fibula musculocutaneous flap was 100% (13/13), and one patient had complications (partial necrosis at the edge of the flap). The follow-up period was 7 to 15 months, and the median time was 10 months. All patients achieved a healing effect. The number of cases with an increase in mouth opening ≥ 1 cm, 0.5 cm ≤ mouth opening increase < 1 cm, and mouth opening increase < 0.5 cm were 5, 6, and 2, respectively. An imaging examination showed that 12 patients had good bone healing, and 1 patient did not completely heal 7 months after operation. The denture restoration was 92.3% (12/13), of which 3 cases were implanted and repaired at the same time. The average chewing efficiency was 56.11% ± 7.12% (42.03%-67.83%). Conclusion Virtual surgical planning is an effective method for the surgical treatment of mandibular osteoradionecrosis, which can reduce the risk of surgery and more effectively perform mandibular shape and function repair.

Objective : To investigate the differential expression of mitochondrial microRNAs (mitomiRs) in tongue squamous cell carcinoma (TSCC) and to screen out mitomiRs related to chemotherapy resistance. Methods : Mitochondrial, cytoplasmic, and total cellular RNAs were extracted from the squamous cell carcinoma cell line CAL-27 and the cisplatin-resistant cell line CAL-27-re. High-throughput miRNA microarrays were used to screen for differentially expressed mitomiRs between the drug-resistant and parental cells. The upregulated mitomiRs in the CAL-27 and CAL-27-re cells and in samples from chemoresistant and chemosensitive tongue squamous cell carcinoma patients were verified by qRT-PCR. Results: The microarray detected 263 miRNAs in 6 components of the mitochondrial, cytoplasmic and total cellular RNAs from the CAL-27 and CAL-27-re cells, including 57 mitomiRs and 134 cytoplasmic microRNAs (cytomiRs). Compared with the total miRNAs, 35 mitomiRs were upregulated in the CAL-27-re cells, and 31 mitomiRs were upregulated in the CAL-27 cells (≥ 1.5-fold). Further comparative analysis of mitomiRs that were differentially expressed between the parental and drug-resistant cells identified 11 upregulated mitomiRs (miR-2392, miR-4462, miR-1290, miR-4449, miR-1268a, miR-1246, and miR-371a-5p, miR-3934-5p, miR-4271, miR-513p, and miR-664b-3p) and 5 downregulated mitomiRs (miR-188-5p, miR-1973, miR -3653, miR-4499, and miR-5787); the expression levels of the other 41 mitomiRs were almost identical in both cell lines. The qRT-PCR results were consistent with the miRNA microarray results. The 11 upregulated mitomiRs that were validated between the CAL-27 and CAL-27-re cells included miR-1268a, miR-2392, miR-4462, and miR-1290. Additionally, 5 mitomiRs, including miR-4449, were upregulated in the clinical chemotherapy-resistant tongue squamous cell carcinoma samples. Conclusion Differentially expressed mitomiRs were found between cisplatin-resistant and cisplatin-sensitive tongue squamous cell carcinoma cells. mitomiRs with high expression levels (miR-2392, miR-4462, miR-1290, miR-4449 and miR-1268a) may play important roles in the drug resistance of tongue squamous cell carcinoma.

Objective To investigate the regulatory mechanism of Paraquat (PQ)-induced epithelial-mesenchymal transition (EMT) and the protective mechanism of N-acetyl-cysteine (NAC) in PQ-induced A549 cells by EMT markers (E-cadherin and α-smooth muscle actin).Methods EMT model was established by 30 μmol/L PQ-exposed A549 cells for 4 d.The application of 10 mmol/L NAC was incubated with A549 cells for 2 h in advance.Morphological changes of A549 cells were observed under light microscope.Western blot was used to detect the expression levels of TGF-β1,E-cadherin and α-smooth muscle actin.Results In PQ-induced EMT model,the PQ group showed typical morphological changes,and the cells changed from cobblestone-like epithelial appearance to spindle-shaped mesenchymal-like appearance compared to the control group.Westem blotting showed that the protein levels of TGF-β1 and α-smooth muscle actin in the PQ group were significantly increased and the protein levels of E-cadherin were decreased in the PQ group (all P＜0.05).NAC preincubation can effectively reverse the above changes caused by PQ exposure:the protein levels of E-cadherin and α-smooth muscle actin were significantly increased and decreased,respectively and morphological changes showed more cobblestonelike epithelial appearance.Conclusion Cell experiments showed that PQ exposure can cause EMT in epithelial cells,and NAC has a protective effect in this process.Thus,it may provide new ideas and strategies for the treatment of pulmonary fibrosis caused by PQ poisoning in clinical practice.