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 impact of various conditions on the adsorption of quetiapine by activated carbon, establish a method for evaluating the adsorption efficacy of activated carbon on quetiapine, and assess the adsorption effects both in vitro and in vivo.Methods:In vitro experiments involved incubating activated carbon with quetiapine under different conditions, including varying organic solvent contents, types of organic solvents, adsorption temperatures, adsorption times, and pH. After reaching equilibrium, the mixtures were centrifuged, and the supernatants were collected. The concentration of quetiapine in the supernatants was measured using LC-MS/MS, and the adsorption rates were calculated. The log-transformed concentration of activated carbon was used as the independent variable and the adsorption rate as the dependent variable for function fitting using Origin 2021 software. In the in vivo experiments, rats were administered quetiapine orally, followed by 125 mg/mL of activated carbon in the experimental group. Blood samples were collected at multiple time points pre- and post-administration (0.17 h, 0.33 h, 0.50 h, 0.75 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, 12 h, and 24 h). Plasma samples were pre-treated and the quetiapine concentrations were determined using LC-MS/MS. Pharmacokinetic parameters for both control and experimental groups were calculated using DAS 2.0 software.Results:The factors such as organic solvent content, type of organic solvent, adsorption temperature, adsorption time, and pH value significantly influenced the adsorption efficiency of quetiapine by activated carbon, leading to the optimization and standardization of the in vitro adsorption methodology. Among the 100 different adsorption function models tested, the Boltzmann function was identified as the most suitable models for describing the adsorption of quetiapine by activated carbon. Pharmacokinetic analysis showed that the experimental group treated with activated carbon exhibited significantly reduced C max and AUC for quetiapine compared to the control group. Conclusion:The results of both in vitro and in vivo experiments demonstrate that activated carbon effectively adsorbs quetiapine, providing a potential method for mitigating quetiapine absorption.

Humans ; East Asian People ; Surveys and Questionnaires ; Vitiligo/epidemiology*

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.

Monitoring neuronal activity in vivo is critical to understanding the physiological or pathological functions of the brain. Two-photon Ca imaging in vivo using a cranial window and specific neuronal labeling enables real-time, in situ, and long-term imaging of the living brain. Here, we constructed a recombinant rabies virus containing the Ca indicator GCaMP6s along with the fluorescent protein DsRed2 as a baseline reference to ensure GCaMP6s signal reliability. This functional tracer was applied to retrogradely label specific V1-thalamus circuits and detect spontaneous Ca activity in the dendrites of V1 corticothalamic neurons by in vivo two-photon Ca imaging. Notably, we were able to record single-spine spontaneous Ca activity in specific circuits. Distinct spontaneous Ca dynamics in dendrites of V1 corticothalamic neurons were found for different V1-thalamus circuits. Our method can be applied to monitor Ca dynamics in specific input circuits in vivo, and contribute to functional studies of defined neural circuits and the dissection of functional circuit connections.

To explore the effect of growth hormone releasing peptide (GHRP) on myocardial cell apoptosis in heart failure (HF) rats. Methods: Rat's HF model was established by the ligation of left anterior descending coronary artery induced ischemia. 40 male SD rats were randomly assigned into 4 groups: Normal control group, Sham operation group, HF group and GHRP treated HF group. n=10 in each group and the rats were fed for 4 weeks after the operation. Cardiac function was examined and myocardial cell morphology was observed; protein expressions of Smac/DIABL0 and Bcl-2 were measured by Western blot analysis; cell apoptosis was evaluated by FCM technique. The differences for above parameters were compared among groups to explore the effect of GHRP on myocardial cell apoptosis in HF rats. Results: Compared with HF group, GHRP treated HF group showed the less heart dilation, higher LVEF, lighter pathological changes in myocardial cells and decreased protein expression of Smac/DIABL0, all P<0.05. Bcl-2 level was lower in HF group than the other 3 groups, P<0.05. Compare with Normal control group, GHRP treated HF group had elevated Bcl-2 level, all P<0.05. Myocardial cell apoptosis index was different between HF group and GHRP treated HF group, P<0.05. Conclusion: The effect of GHRP on anti-HF should be via inhibiting myocardial cell apoptosis; the mechanism may partly be through promoting Bcl-2 protein expression and depressing Smac/DIABLO mediated mitochondrial pathway of apoptosis.

To evaluate the effectiveness and safety of transvaginal cervical cerclage and to investigate the influencing factors in prognosis. Methods The medical records of 85 cases who underwent transvaginal cervical cerclage in Peking Union Medical College Hospital from January, 1985 to September, 2011 were reviewed. Patients with a typical history of recurrent preterm birth/second trimester miscarriage, or for whom the 8.0 mm Hegar uterine dilator could be pushed through the internal cervical os without resistance during the non-pregnancy period were included in the elective cerclage group (n=69) and those diagnosed as cervical insufficiency during pregnancy were included in the emergency cerclage group (n=16). The numbers of premature birth/second trimester miscarriage, gestational age at cerclage, gestational age at delivery and its influencing factors were compared between the two groups. T test, rank sum test and Fisher's exact test were used for statistical analysis. Results All patients underwent cerclage between 13+3 and 26+6 weeks of gestation without major complications, such as rupture of membrane, placental abruption or bladder injury. Patients in the elective cerclage group underwent the procedure significantly earlier than those in the emergency cerclage group [16.6(15.4, 18.3)vs 22.7(19.5, 24.6)weeks, Z=-5.140, P<0.05]. Nine cases had lost to follow-up. Among the remaining 76 cases, the rate of infection after surgery was 18.4%(14/76);the rate of abortion was 17.1%(13/76); and the rate of live birth was 82.9%(63/76). The live birth rate of the emergency group was lower than that of the elective cerclage group [9/15 vs 88.5%(54/61), Fisher's exact test, P<0.05]. Apparent infection after surgery was observed more frequently in the emergency group than that in the elective cerclage group [6/15 vs 13.1% (8/61), Fisher's exact test, P<0.05]. Uterine malformation, infection after surgery and latent infection befor surgery were unfavorable factors associated with miscarriage and early preterm labor. Conclusions Transvaginal cervical cerclage is a safe and effective treatment for cervical insufficiency. Elective cervical cerclage is superior to emergent cerclage. Emphasis should be placed on the monitoring and treatment of perioperative infection. Cervical cerclage should be undertaken with caution in patients with uterine malformation.

BACKGROUND:Transplantation of stem cells has a beneficial effect on myocardium revascularization and improving cardiac function after myocardial infarction, and HLA-G protein contributes to the formation and maintenance of the immune tolerance.
OBJECTIVE:To investigate the transplantation effects of human umbilical cord mesenchymal stem cells at different gestational age with different HLA-G expression levels on myocardium revascularization after myocardial infarction in rabbits.
METHODS:Thirty healthy New Zealand rabbits were selected and were randomly divided into human smal gestational age umbilical cord-derived mesenchymal stem cells transplantation group, human ful-term umbilical cord-derived mesenchymal stem cells transplantation group and control group. After the rabbits models of acute myocardial infarction had been established, the former two groups were infused different umbilical cord-derived human umbilical cord mesenchymal stem cells labeled with 5-bromo-2-deoxyuridine into the edge and center of myocardial infarct region by multipoint injection. Rabbits in the control group were subjected to an equal volume of serum-free culture medium.
RESULTS AND CONCLUSION:Four weeks after celltransplantation, 5-bromo-2-deoxyuridine-positive cells were found surrounding the infarct site in both transplantation groups. Myocardial fibrosis and myocardial infarct size were significantly lower in both transplantation groups than those of the control group (P<0.05), and there was a significant difference between the two transplantation groups (P<0.01). The positive staining of factor VII indicated that capil ary density was increased significantly in the smal gestational age umbilical cord-derived mesenchymal stem cells transplantation group as compared with the ful-term umbilical cord-derived mesenchymal stem cells transplantation group (P<0.01), and a sstatistical difference was found between two transplantation groups and the control group (P<0.01). Transplantation of human umbilical cord mesenchymal stem cells with high HLA-G expression increases new capil ary vessels and improves myocardium revascularization. Al indicate that human smal gestational age umbilical cord mesenchymal stem cells have the potential to become the better source of cardiomyocytes transplantation.

10.3969/j.issn.1008-9691.2013.03.004

A retrospective analysis was carried out in 220 cases of nonfunctional pituitary adenoma (NFA).The diagnosis was based on negative immunohistochemical staining,no elevation of plasma hormone level,and no symptom caused by increased hormone level.Incidence of NFA was the highest(33.13％) among the pituitary tumors.It was more common in males than in females (132 ∶ 88).The highest prevalence resided in the elder group.N FA often caused pituitary apoplexy,and mainly presented as compression symptoms including visual field abnormalities (85.00％),headache (80％),hypopsia (68.66％),and other symptoms of hypopituitarism (44.04％).Imaging features showed tumor size usually within 2-4 cm (71.82％),and aggregated degree Ⅲ or Ⅳ (83.64％).