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 evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To understand the current status of oral frailty in elderly diabetic patients and analyze its influencing factors.Methods:A convenience sampling method was used to select elderly diabetic patients hospitalized at Henan Cancer Hospital and Henan Provincial People's Hospital from October 2023 to May 2024. The general information questionnaire, Oral Frailty Index-8 (OFI-8) , Short Form of Health Literacy Dental Scale (HeLD-14) , Nutritional Risk Screening 2002 (NRS 2002) , and the Diabetes Distress Scale (DDS) were used to collect data. Binary Logistic regression analysis was used to examine the influencing factors of oral frailty in elderly diabetic patients.Results:A total of 235 questionnaires were distributed, and 220 valid questionnaires were returned, with an effective response rate of 93.62% (220/235) . The incidence of oral frailty in elderly diabetic patients was 46.82% (103/220) . The binary Logistic regression analysis showed that glycated hemoglobin, dry mouth, remaining teeth, nutritional risk, oral health literacy, and diabetes distress were significant influencing factors for the occurrence of oral frailty in elderly diabetic patients ( P<0.05) . Conclusions:The current status of oral frailty in elderly diabetic patients is concerning. Healthcare providers should pay attention to the oral health status of elderly diabetic patients and provide targeted nursing interventions and recommendations based on the influencing factors of oral frailty, in order to reduce its occurrence.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To understand the current status of oral frailty in elderly diabetic patients and analyze its influencing factors.Methods:A convenience sampling method was used to select elderly diabetic patients hospitalized at Henan Cancer Hospital and Henan Provincial People's Hospital from October 2023 to May 2024. The general information questionnaire, Oral Frailty Index-8 (OFI-8) , Short Form of Health Literacy Dental Scale (HeLD-14) , Nutritional Risk Screening 2002 (NRS 2002) , and the Diabetes Distress Scale (DDS) were used to collect data. Binary Logistic regression analysis was used to examine the influencing factors of oral frailty in elderly diabetic patients.Results:A total of 235 questionnaires were distributed, and 220 valid questionnaires were returned, with an effective response rate of 93.62% (220/235) . The incidence of oral frailty in elderly diabetic patients was 46.82% (103/220) . The binary Logistic regression analysis showed that glycated hemoglobin, dry mouth, remaining teeth, nutritional risk, oral health literacy, and diabetes distress were significant influencing factors for the occurrence of oral frailty in elderly diabetic patients ( P<0.05) . Conclusions:The current status of oral frailty in elderly diabetic patients is concerning. Healthcare providers should pay attention to the oral health status of elderly diabetic patients and provide targeted nursing interventions and recommendations based on the influencing factors of oral frailty, in order to reduce its occurrence.

Objective:To analyze the current status, hotspots, and development trends of prone position ventilation in critically ill patients.Methods:The literature on prone position ventilation in critically ill patients was electronically retrieved in the Web of Science core collection and China National Knowledge Infrastructure, with a search period from January 1, 1998 to July 1, 2023. CiteSpace 6.2.R4 was used to analyze articles.Results:A total of 585 articles on prone position ventilation in critically ill patients were included, consisting of 162 in Chinese and 423 in English. In recent years, the number of research articles on prone position ventilation for critically ill patients, both domestically and internationally, showed a progressive upward trend. Foreign research hotspots included acute respiratory distress syndrome, pressure injury, infants, critically ill patients, electrical impedance imaging, epidemiology, enteral nutrition, volume responsiveness, and pulmonary recruitment. Domestic research hotspots involved mechanical ventilation, respiration, pressure injury, mortality, and respiratory failure.Conclusions:Research on prone position ventilation in critically ill patients is receiving increasing attention. Chinese researchers can further explore based on previous research and strengthen communication and cooperation across fields and institutions.

Objective:To observe the clinical effect of free posterior interosseous artery perforator flap carrying superficial vein for reconstructing severe perioral scar hyperplasia and contracture.Methods:The retrospective observational study method was used. From August 2019 to March 2023, 11 patients with severe perioral scar hyperplasia and contracture after severe facial burns who met the inclusion criteria were admitted to General Hospital of TISCO (the Sixth Hospital of Shanxi Medical University). All patients were male and aged 23 to 56 years, with an average age of 31.3 years. After the perioral scar was removed and released, the wound area was 3.0 cm×2.0 cm to 10.5 cm×2.0 cm. The free posterior interosseous artery perforator flap carrying superficial vein was used to repair the wound, and the flap incision area was 3.5 cm×2.5 cm to 11.0 cm×2.5 cm. Among them, 6 patients required repair of wounds after resecting scar around ipsilateral upper and lower lips, and the lobular treatment of the flap was conducted. The wound in the flap donor area was directly sutured. After surgery, the survival of the flap and the occurrence of vascular crisis were observed. During follow-up after surgery, the appearance, texture, and color of the flap, the appearance of the flap donor area, and improvements of crooked mouth, drooling, limited mouth opening, and lip valgus in patients were observed.Results:All the flaps in patients completely survived after surgery, with no occurrence of vascular crisis. During follow-up of 6 to 36 months after surgery, the flap was not significantly bloated, was soft in texture, and had a similar color to that of the normal facial skin. Only linear scars were left in the flap donor area, and crooked mouth, drooling, limited mouth opening, and lip valgus in patients were significantly improved.Conclusions:The free posterior interosseous artery perforator flap carrying superficial vein can reconstruct severe perioral scar hyperplasia and contracture, with low incidence of postoperative flap vascular crisis, and the lobular treatment of flaps can repair wounds around unilateral upper and lower lips at the same time. After surgery, the appearance and function of the perioral area are significantly improved. The flap is a good choice for repairing small area of severe perioral scar hyperplasia and contracture.

Differing from other subtypes of inhibitory interneuron, chandelier or axo-axonic cells form depolarizing GABAergic synapses exclusively onto the axon initial segment (AIS) of targeted pyramidal cells (PCs). However, the debate whether these AIS-GABAergic inputs produce excitation or inhibition in neuronal processing is not resolved. Using realistic NEURON modeling and electrophysiological recording of cortical layer-5 PCs, we quantitatively demonstrate that the onset-timing of AIS-GABAergic input, relative to dendritic excitatory glutamatergic inputs, determines its bi-directional regulation of the efficacy of synaptic integration and spike generation in a PC. More specifically, AIS-GABAergic inputs promote the boosting effect of voltage-activated Na⁺ channels on summed synaptic excitation when they precede glutamatergic inputs by >15 ms, while for nearly concurrent excitatory inputs, they primarily produce a shunting inhibition at the AIS. Thus, our findings offer an integrative mechanism by which AIS-targeting interneurons exert sophisticated regulation of the input-output function in targeted PCs.
Axon Initial Segment ; Axons/physiology* ; Neurons ; Synapses/physiology* ; Pyramidal Cells/physiology* ; Interneurons/physiology* ; Action Potentials/physiology*

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R² = 0.033; P = 0.018), followed by acute kidney injury (AKI; R² = 0.032; P = 0.011) and plasma MIP-1β level (R² = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.
Acute Kidney Injury/complications* ; Bacteria/classification* ; Chemokine CCL4/blood* ; Community-Acquired Infections/microbiology* ; Humans ; Lung ; Microbiota/genetics* ; Pneumonia, Bacterial/diagnosis* ; Prognosis ; RNA, Ribosomal, 16S/genetics*

Objective:To explore the application value of artificial intelligence-assisted diagnosis system for TBS report in cervical cancer screening.Methods:A total of 16 317 clinical samples and related data of cervical liquid-based thin-layer cell smears, which were obtained from July 2020 to September 2020, were collected from Southern Hospital, Guangzhou Huayin Medical Inspection Center, Shenzhen Bao′an People′s Hospital(Group) and Changsha Yuan′an Biotechnology Co., Ltd. The TBS report artificial intelligence-assisted diagnosis system of cervical liquid-based thin-layer cytology jointly developed by Southern Medical University and Guangzhou F. Q. PATHOTECH Co., Ltd. based on deep learning convolution neural network was used to diagnose all clinical samples. The sensitivity,specificity and accuracy of both artificial intelligence-assisted diagnosis system and cytologists using artificial intelligence-assisted diagnosis system were analyzed based on the evaluation standard(2014 TBS). The time spent by the two methods was also compared.Results:The sensitivity of artificial intelligence-assisted diagnosis system in predicting cervical intraepithelial lesions and other lesions (including endometrial cells detected in women over 45 years old and infectious lesions) under different production methods, different cytoplasmic staining and different scanning instruments was 92.90% and 83.55% respectively, and the specificity of negative samples was 87.02%, while that of cytologists using artificial intelligence-assisted diagnosis system was 99.34%, 97.79% and 99.10%, respectively. Moreover, cytologists using artificial intelligence-assisted diagnosis system could save about 6 times of reading time than manual.Conclusions:Artificial intelligence-assisted diagnosis system for TBS report of cervical liquid-based thin-layer cytology has the advantages of high sensitivity, high specificity and strong generalization. Cytologists can significantly improve the accuracy and work efficiency of reading smears by using artificial intelligence-assisted diagnosis system.