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 explore the application of anterior esophageal wall full layer fixation and gastric tube guidance in total laparoscopic overlap method for intracorporeal esophagojejunostomy.Methods:Overlap esophagojejunostomy with anterior esophageal wall full layer fixation and gastric tube guidance is suitable for patients with advanced gastric cancer (clinical stage: cT1b~4aN0~3M0) and esophageal invasion <3 cm, who underwent radical total gastrectomy+ overlap esophagojejunostomy. The main operation procedure was performed as follows: A titanium clip was used for fixation of the full anterior wall of esophagus before overlap esophagojejunostomy, and the side‐to‐side esophagojejunostomy was performed with the linear stapler under the guidance of gastric tube. Then the titanium clip was removed after confirming that the correct cavity was entered. Finally, the common outlet was closed by two barbed sutures. A descriptive case series study was conducted. The clinical data of patients who underwent laparoscopic radical gastrectomy and overlap esophagojejunostomy with anterior esophageal wall full layer fixation and gastric tube guidance in Guangdong Provincial Hospital of Chinese medicine and the First Affiliated Hospital of Guangzhou University of Chinese medicine from May 2021 to June 2023 were retrospectively analyzed.Results:A total of 42 patients were collected, and all of them were successfully completed laparoscopic total radical gastrectomy without conversion to laparotomy or perioperative death. The esophagojejunostomy time, operative time, intraoperative blood loss was 17(5‐25) minutes, (258.8±38.0) minutes and 50(20‐200) ml, respectively. The incidence of esophageal false lumen was 0%, and there were no intraoperative complications. The time of gastric tube removal, initial fluid diet intake and the duration of postoperative hospital were 2(1‐5) , 4(1‐8) and 8(4‐21) days, respectively. There were no postoperative anastomotic hemorrhage, anastomotic stenosis and other related complications. One patient (2.38%) developed a Clavien‐Dindo IIIb complication, which was abdominal hemorrhage after operation. The second surgical exploration confirmed that the patient was bleeding due to gastroduodenal artery rupture. After intraoperative suture hemostasis, fluid expansion, blood transfusion and other treatments, the patient was discharged on the 15th day after the operation. Three patients (7.14%) developed Clavien‐Dindo grade II complications, including anastomotic leakage, chylous leakage and pulmonary infection, and were discharged after conservative treatment such as anti‐infection and prolonged retention of drainage tube.Conclusions:Laparoscopic overlap method for intracorporeal esophagojejunostomy with anterior esophageal wall fixation and gastric tube guidance can shorten the time of esophagojejunostomy and prevent the occurrence of false lumen, and do not increase anastomose‐related complications.

Diabetic ulcer （DU） wound is one of the chronic and serious complications of diabetes characterized by prolonged wound healing， and it is more common in foot and lower extremity ulcers. DU has brought great economic and psychological pressure to patients and seriously affected the quality of life of patients because of its great difficulty in treatment， long treatment process， and high morbidity and mortality. Therefore， how to help the rapid healing of DU wounds， reduce the disability rate and mortality rate， protect limb function， and improve the quality of life is an important topic and hot spot in the field of medical research. The pathogenesis of DU is complex， mainly including microcirculation disorder， peripheral neuropathy， inflammation and infection， and excessive apoptosis of cells， involving physiological processes such as wound inflammation， granulation tissue hyperplasia and re-epithelialization. A large number of previous studies have found that Chinese medicine can regulate phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Notch， nuclear factor E₂-related factor 2 （Nrf2）， transforming growth factor-β （TGF-β）/Smad， and other signaling pathways， regulate abnormal glucose metabolism， improve microcirculation， inhibit inflammation and oxidative stress， regulate cell proliferation and excessive apoptosis， and promote wound tissue growth to promote the rapid healing of DU wounds under the guidance of treatment based on traditional Chinese medicine （TCM） syndrome differentiation and internal and external treatment. Therefore， this paper reviewed Chinese medicinal monomers or Chinese medicinal compounds in recent years in regulating the above signaling pathways and the expression of key protein molecules and promoting the rapid healing of DU wounds， aiming to provide ideas and a theoretical basis for the in-depth study and clinical application of Chinese medicine in promoting the healing of DU wounds.

Objective:To explore the application of anterior esophageal wall full layer fixation and gastric tube guidance in total laparoscopic overlap method for intracorporeal esophagojejunostomy.Methods:Overlap esophagojejunostomy with anterior esophageal wall full layer fixation and gastric tube guidance is suitable for patients with advanced gastric cancer (clinical stage: cT1b~4aN0~3M0) and esophageal invasion <3 cm, who underwent radical total gastrectomy+ overlap esophagojejunostomy. The main operation procedure was performed as follows: A titanium clip was used for fixation of the full anterior wall of esophagus before overlap esophagojejunostomy, and the side‐to‐side esophagojejunostomy was performed with the linear stapler under the guidance of gastric tube. Then the titanium clip was removed after confirming that the correct cavity was entered. Finally, the common outlet was closed by two barbed sutures. A descriptive case series study was conducted. The clinical data of patients who underwent laparoscopic radical gastrectomy and overlap esophagojejunostomy with anterior esophageal wall full layer fixation and gastric tube guidance in Guangdong Provincial Hospital of Chinese medicine and the First Affiliated Hospital of Guangzhou University of Chinese medicine from May 2021 to June 2023 were retrospectively analyzed.Results:A total of 42 patients were collected, and all of them were successfully completed laparoscopic total radical gastrectomy without conversion to laparotomy or perioperative death. The esophagojejunostomy time, operative time, intraoperative blood loss was 17(5‐25) minutes, (258.8±38.0) minutes and 50(20‐200) ml, respectively. The incidence of esophageal false lumen was 0%, and there were no intraoperative complications. The time of gastric tube removal, initial fluid diet intake and the duration of postoperative hospital were 2(1‐5) , 4(1‐8) and 8(4‐21) days, respectively. There were no postoperative anastomotic hemorrhage, anastomotic stenosis and other related complications. One patient (2.38%) developed a Clavien‐Dindo IIIb complication, which was abdominal hemorrhage after operation. The second surgical exploration confirmed that the patient was bleeding due to gastroduodenal artery rupture. After intraoperative suture hemostasis, fluid expansion, blood transfusion and other treatments, the patient was discharged on the 15th day after the operation. Three patients (7.14%) developed Clavien‐Dindo grade II complications, including anastomotic leakage, chylous leakage and pulmonary infection, and were discharged after conservative treatment such as anti‐infection and prolonged retention of drainage tube.Conclusions:Laparoscopic overlap method for intracorporeal esophagojejunostomy with anterior esophageal wall fixation and gastric tube guidance can shorten the time of esophagojejunostomy and prevent the occurrence of false lumen, and do not increase anastomose‐related complications.

The accumulation of pathological α-synuclein (α-syn) in the central nervous system and the progressive loss of dopaminergic neurons in the substantia nigra pars compacta are the neuropathological features of Parkinson's disease (PD). Recently, the findings of prion-like transmission of α-syn pathology have expanded our understanding of the region-specific distribution of α-syn in PD patients. Accumulating evidence suggests that α-syn aggregates are released from neurons and endocytosed by glial cells, which contributes to the clearance of α-syn. However, the activation of glial cells by α-syn species produces pro-inflammatory factors that decrease the uptake of α-syn aggregates by glial cells and promote the transmission of α-syn between neurons, which promotes the spread of α-syn pathology. In this article, we provide an overview of current knowledge on the role of glia and α-syn pathology in PD pathogenesis, highlighting the relationships between glial responses and the spread of α-syn pathology.
Humans ; Parkinson Disease/pathology* ; alpha-Synuclein/metabolism* ; Dopaminergic Neurons/metabolism* ; Pars Compacta/metabolism*

AIM:To assess the clinical efficacy of 5-fluorouracil(5-FU)and bandage contact lens in the pterygium excision combined with autogenous limbal stem cell transplantation(ALSCT)in treating patients with pterygium.METHODS:Random controlled clinical trial. A total of 71 patients(71 eyes)of pterygium who treated at the department of ophthalmology in Qinhuangdao Haigang Hospital between May 2021 and November 2022 were included. They were divide into three groups, including 23 eyes received pterygium excision combined with ALSCT in group A, 24 eyes that were administered with 5-FU intraoperatively and postoperatively in group B, and 24 eyes that received both bandage contact lens and 5-FU in group C. Furthermore, comfort levels at 1, 3, 7, 14d postoperatively, corneal epithelial healing at 1, 3, 7, 14d and 1mo postoperatively, treatment outcomes and complications at 3～6mo postoperatively were compared among the three groups of patients.RESULTS:The comfort levels at 1, 3 and 7d postoperatively and corneal healing at 1 and 3d postoperatively of the group C were better than those of the groups A and B. There were no statistical significant differences in the comfort levels at 14d after surgery and corneal healing at 14d and 1mo after surgery among the three groups of patients. Over a 3～6mo follow-up period, group A experienced recurrence in 3 eyes, group B had 1 recurrence, while group C had no recurrence. There were no statistically significant differences in complication rates among the three groups of patients.CONCLUSIONS: The application of 5-FU combined with bandage contact lens can enhance postoperative comfort levels, promote corneal epithelial healing, and improve the success rate in pterygium excision combined with ALSCT.

【Objective】 To observe the effect of Xiaozhongzhitong Mixture on ischemia-reperfusion injury of rat skin flaps and p38MAPK-PPARγ/NF-κB signaling pathway. 【Methods】 After flap operation, the survival of rat back flaps and flap survival rate were observed. HE staining, TUNEL staining, and qRT-PCR were used to detect the degree of nuclear destruction, as well as the distribution characteristics and mRNA expression levels of p38MAPK, PPARγ, and Nf-κB in vascular endothelial cells of rat flaps, respectively. 【Results】 The flap survival area in sham operation group was the largest, and it was the smallest in model control group and PPARγ inhibitor group. HE staining and TUNEL staining results showed that the flap tissue cells of rats in model control group and PPARγ inhibitor group were severely damaged and obvious apoptotic cells were seen. In model group, rats’ skin flap tissue cells were arranged in a single layer, and the nucleus was intact and clear. qRT-PCR experiment results showed that compared with model group, the expressions of p38MAPK and Nf-κb in the flap tissue of rats in Xiaozhong Zhicong Mixture group were inhibited (P<0.05), while the expression of PPARγ was increased (P<0.05). When the blocker was added, the expressions of p38MAPK, NF-κB and PPARγ in the flap tissue were further suppressed. 【Conclusion】 Xiaozhongzhitong Mixture can alleviate the infiltration of inflammatory cells in the rat model of skin flap ischemia-reperfusion injury, reduce inflammation and the production of apoptotic cells, thereby alleviating the ischemia-reperfusion injury of skin flaps and promoting the survival of the flaps. The mechanism may be related to the inhibition of p38MAPK-PPARγ/NF-κB signaling pathway.

Objective:To investigate the differences of integral alpha 3 (ITGA3) mRNA and protein expressions in gliomas of different grades and different cell lines, and gliomas tissues of different clinical and molecular characteristics, and evaluate their prognostic values in brain glioma patients.Methods:(1) ITGA3 mRNA expression data in the brain gliomas and clinical data of these glioma patients were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). The differences of ITGA3 mRNA expressions in glioma patients with different gender, ages, WHO grading, isocitrate dehydrogenase 1 ( IDH) mutation statuses, and 1p/19q co-deletion statuses were compared. Kaplan-Meier method was used to plot and compare the survival curves of patients with ITGA3 mRNA high expression and ITGA3 mRNA low expression. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficiency of ITGA3 mRNA expression in survival rate of gliomas. Univariate and multivariate Cox regression analyses were used to explore the independent influencing factors for prognoses in glioma patients. The independent influencing factors for prognosis were used to construct nomograms and the calibration diagram was used to verify the reliability of nomograms in predicting the prognoses of these patients. (2) Intracellular localization of ITGA3 and ITGA3 protein expression in low- and high-grade gliomas were determined by on-line database of Human Protein Atlas (HPA). (3) Brain glioma cells U87, U118, U251 and human astrocytes SVG were cultured in vitro, and the ITGA3 mRNA and protein expressions in cells were detected by Western blotting and reverse transcription (RT)-PCR, respectively. Results:(1) In TCGA database, the ITGA3 mRNA expressions in gliomas of WHO grading II, III and IV increased successively, with significant differences (P<0.05). In CGGA database, the ITGA3 mRNA expression in glioma of WHO grading IV was statistically higher than that in glioma of WHO grading II and III ( P<0.05). In TCGA and CGGA databases, the ITGA3 mRNA expressions in glioma patients aged ≤40 years and >40 years, patients with IDH wild-type and IDH mutation, and patients with chromosome 1p/19q deletion and chromosome 1p/19q non-deletion were statistically different ( P<0.05). The survival rate of patients with low ITGA3 mRNA expression was significantly higher than that of patients with high ITGA3 mRNA expression, no matter in low-grade glioma, glioblastoma, or entire glioma samples ( P<0.05). ROC curve showed that, in TCGA database, the area under the curve (AUC) of ITGA3 mRNA in predicting 1, 3, and 5 years survival was 0.791, 0.786, and 0.708 in glioma patients; in CGGA database, the AUC of ITGA3 mRNA in predicting 1, 3, and 5 years survival was 0.661, 0.667, and 0.659. Multivariate Cox regression analysis showed that, in TCGA database, age, WHO grading, IDH mutation, chromosome 1p/19q deletion and ITGA3 mRNA expression ( HR=1.018, 95%CI: 1.006-1.030, P=0.0.003) were independent influencing factors for prognoses of glioma patients ( P<0.05); and in CGGA database, WHO grading, IDH mutation, chromosome 1p/19q deletion, and ITGA3 mRNA expression ( HR=1.445, 95%CI: 1.132-1.844, P=0.003) were independent influencing factors for prognoses of glioma patients ( P<0.05). Nomograms showed that age had the greatest influence in survival, followed by ITGA3 mRNA expression. Calibration plots showed that nomogram was reliable in predicting 1-, 3-, and 5-year survival in glioma patients. (2) Immunofluorescence localization showed that ITGA3 protein mainly aggregated in cell membrane and vesicles. Immunohistochemical staining showed that the ITGA3 protein expression in high-grade glioma tissues was obviously higher than that in low-grade glioma tissues. (3) The results of RT-PCR and Western blotting revealed that the ITGA3 mRNA and protein expressions in glioma cell lines U87, U118 and U251 were significantly higher than those in SVG cells ( P<0.05). Conclusion:The ITGA3 mRNA and protein expression levels are correlated with the malignant degrees of glioma; patients with ITGA3 mRNA low expression tend to have a high overall survival; ITGA3 mRNA expression can be used as an index to evaluate the prognoses of glioma patients.

Idiopathic thrombocytopenic purpura (ITP) is a common bloody disease with a high incidence in children, but its diagnostic method is exclusive diagnosis, and the existing detection techniques are mostly invasive, which may cause secondary injury to patients and also may increase the risk of disease. In order to make up for the lack of the detection method, this study made a preliminary exploration on the diagnosis of children's ITP from the perspective of infrared thermography. In this study, a total of 11 healthy children and 22 ITP children's frontal infrared thermal images were collected, and the pattern characteristic (PFD), average temperature (Troi) and maximum temperature (MAX) characteristics of 7 target areas were extracted. The weighted PFD parameters were correlated with the platelet count commonly used in clinical diagnosis, and the sensitivity and specificity of the weighted PFD parameters for children's ITP were calculated through the receiver operating characteristic curve (ROC). The final results showed that the difference of the weighted PFD parameters between healthy children and ITP children was statistically significant, and the parameters negatively correlated with platelet count. Under the ROC curve, the area under the curve (AUC) of this parameter is as high as 92.1%. Based on the research results of this paper, infrared thermography can clearly show the difference between ITP children and healthy children. It is hoped that the methods proposed in this paper can non-invasively and objectively describe the characteristics of ITP infrared thermal imaging of children, and provide a new ideas for ITP diagnosis.
Area Under Curve ; Child ; Humans ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; Thermography

Since the discovery of the C9ORF72 gene in 2011, great advances have been achieved in its genetics and in identifying its role in disease models and pathological mechanisms; it is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ALS patients with C9ORF72 expansion show heterogeneous symptoms. Those who are C9ORF72 expansion carriers have shorter survival after disease onset than non-C9ORF72 expansion patients. Pathological and clinical features of C9ORF72 patients have been well mimicked via several models, including induced pluripotent stem cell-derived neurons and transgenic mice that were embedded with bacterial artificial chromosome construct and that overexpressing dipeptide repeat proteins. The mechanisms implicated in C9ORF72 pathology include DNA damage, changes of RNA metabolism, alteration of phase separation, and impairment of nucleocytoplasmic transport, which may underlie C9ORF72 expansion-related ALS/FTD and provide insight into non-C9ORF72 expansion-related ALS, FTD, and other neurodegenerative diseases.