Objective:To explore the effectiveness and safety of programmed death 1(PD-1) inhibitory combined with chemotherapy as a neoadjuvant therapy for locally advanced resectable oral squamous cell carcinoma.Methods:This study was a randomized controlled phase Ⅱ trial. Patients recruited from Tianjin Medical University Cancer Institute and Hospital from July 2021 to February 2023 were randomly divided into two groups in a 1∶1 ratio: the experimental group (Toripalimab combined with albumin paclitaxel and cisplatin) and the control group (albumin paclitaxel and cisplatin); patients in both groups underwent three cycles of neoadjuvant therapy. After completion of neoadjuvant therapy, patients were evaluated and subsequent surgical treatment was performed. According to the completion of treatment, the analysis was conducted on both the full analysis set and the protocol set. The effectiveness and safety of treatments were evaluated. SPSS 20.0 software was used for statistical analysis.Results:A total of 41 cases with oral cancer were enrolled, including 26 males and 15 females, aged between 34 and 74 years old. There were 23 cases in the experimental group and 18 cases in the control group. A total of 23 cases completed neoadjuvant therapy and surgery according to the protocol. Experimental group and control group showed respectively the complete response rates of 1/19 and 0/17, the partial response rates of 13/19 and 8/17, the stage-down rates of 4/19 and 3/17, the pathologic complete response rate of 8/14 and 2/9, with no statistically significant differences in individual rates between two groups ( P>0.05). The major pathological response rate of 13/14 in experimental group was higher than that of 2/9 in control group ( P<0.05). The incidence of grade 3-4 adverse reactions related to treatment was low in both groups (4/23 vs. 3/18, χ 2=0.13, P=0.72), and the most common serious adverse reactions in the experimental group were granulocyte deficiency and electrolyte disorder. There were no adverse reactions that affected subsequent surgical treatment or caused death, and the safety and tolerability were good. The median follow-up time was 15 months, and the one-year disease-free survival rate of the experimental group was higher than that of control group (92.86% vs. 77.78%, χ 2=0.62, P=0.42), with a relative decrease of 87% in the risk of disease progression or death ( P=0.029). For patients with programmed death-ligand 1(PD-L1) protein expression combined positive score≥20, the experimental group showed higher major pathological response rate than control group (5/5 vs. 0/4, P=0.03). Conclusion:The neoadjuvant therapy of immunotherapy combined with chemotherapy can improve the pathological remission of oral squamous cell carcinoma and the long-term survival benefits and the prognosis of patients.

Objective:To investigate the learning curve for a five-step procedure, namely, a transthoracic single-port assisted laparoscopic transabdominal diaphragmatic approach, for Siewert type II adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, we analyzed relevant clinical data of 66 patients with Siewert type II adenocarcinoma of the esophagogastric junction who had undergone the five-step procedure performed by the same surgeon in the Gastrointestinal Surgery Department of Guangdong Provincial Hospital of Chinese Medicine from May 2017 to April 2023. The learning curve were plotted using cumulative summation analysis and selected indicators, including intraoperative blood loss, duration of surgery, time to first flatus, time to first tolerance of liquid food, length of hospital stay, and incidence of perioperative complications at different stages were compared. The data were analyzed using SPSS 24.0 statistical software. Numerical data are presented as cases (%) and data were analyzed using the χ 2 test or Fisher's exact test. Normally distributed measurement data are presented as x±s, and independent sample t-testing was performed for inter group comparison. Non-normally distributed measurement data are presented as M( Q1, Q3) and the Mann–Whitney U test was used for inter group comparison. Results:The five-step procedure had been successfully completed without switching to open surgery in all 66 study patients. There were no perioperative deaths, blood loss was 100 (50, 200) mL and duration of surgery 329.4±87.3 minutes. The equation of optimal fit for the duration of surgery was y=0.031x 3-4.4757x 2+164.97x-264.4 ( P<0.001, R2=0.9797). The cumulative summation learning curve reached a vertex when 25 surgical procedures had accumulated. Using 25 cases as the cut-off, we divided the learning curves into learning and proficiency periods and patients into learning (25) and proficiency period groups (41). There were no statistically significant differences between the two groups of patients in sex, age, body mass index, American Society of Anesthesiologists score, history of abdominal surgery, comorbidities, preoperative neoadjuvant therapy, maximum tumor diameter, surgical procedure, or T and N stage of tumor ( P>0.05). The following factors differed significantly (all P<0.05) between the learning and proficiency stages: in the latter there was less intraoperative blood loss (100 [50, 100] ml vs. 200 [100, 200] ml, U=-3.940, P<0.001), shorter duration of surgery ([289.8±50.7] minutes vs. [394.4±96.0] minutes, t=5.034, P<0.001), more mediastinal lymph nodes removed (5 [2, 8] vs. 2 [1, 5], U=-2.518, P=0.012), earlier time to first flatus (2 [2, 3] days vs. 4 [3, 6] days, U=-4.016, P<0.001), earlier time to first tolerance of liquid food (5 [4, 6] days vs. 7 [6, 8] days, U=-2.922, P=0.003), shorter duration of hospital stay (8 [8, 10] vs. 10 [9, 12] days, U=-2.028, P=0.043). The incidence of surgical complications did not differ significantly between the two groups ( P=0.238). Conclusion:Satisfactory results can be achieved with the five-step procedure for patients with Siewert type II adenocarcinoma of the esophagogastric junction once 25 procedures have been performed.

Objective:To investigate the learning curve for a five-step procedure, namely, a transthoracic single-port assisted laparoscopic transabdominal diaphragmatic approach, for Siewert type II adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, we analyzed relevant clinical data of 66 patients with Siewert type II adenocarcinoma of the esophagogastric junction who had undergone the five-step procedure performed by the same surgeon in the Gastrointestinal Surgery Department of Guangdong Provincial Hospital of Chinese Medicine from May 2017 to April 2023. The learning curve were plotted using cumulative summation analysis and selected indicators, including intraoperative blood loss, duration of surgery, time to first flatus, time to first tolerance of liquid food, length of hospital stay, and incidence of perioperative complications at different stages were compared. The data were analyzed using SPSS 24.0 statistical software. Numerical data are presented as cases (%) and data were analyzed using the χ 2 test or Fisher's exact test. Normally distributed measurement data are presented as x±s, and independent sample t-testing was performed for inter group comparison. Non-normally distributed measurement data are presented as M( Q1, Q3) and the Mann–Whitney U test was used for inter group comparison. Results:The five-step procedure had been successfully completed without switching to open surgery in all 66 study patients. There were no perioperative deaths, blood loss was 100 (50, 200) mL and duration of surgery 329.4±87.3 minutes. The equation of optimal fit for the duration of surgery was y=0.031x 3-4.4757x 2+164.97x-264.4 ( P<0.001, R2=0.9797). The cumulative summation learning curve reached a vertex when 25 surgical procedures had accumulated. Using 25 cases as the cut-off, we divided the learning curves into learning and proficiency periods and patients into learning (25) and proficiency period groups (41). There were no statistically significant differences between the two groups of patients in sex, age, body mass index, American Society of Anesthesiologists score, history of abdominal surgery, comorbidities, preoperative neoadjuvant therapy, maximum tumor diameter, surgical procedure, or T and N stage of tumor ( P>0.05). The following factors differed significantly (all P<0.05) between the learning and proficiency stages: in the latter there was less intraoperative blood loss (100 [50, 100] ml vs. 200 [100, 200] ml, U=-3.940, P<0.001), shorter duration of surgery ([289.8±50.7] minutes vs. [394.4±96.0] minutes, t=5.034, P<0.001), more mediastinal lymph nodes removed (5 [2, 8] vs. 2 [1, 5], U=-2.518, P=0.012), earlier time to first flatus (2 [2, 3] days vs. 4 [3, 6] days, U=-4.016, P<0.001), earlier time to first tolerance of liquid food (5 [4, 6] days vs. 7 [6, 8] days, U=-2.922, P=0.003), shorter duration of hospital stay (8 [8, 10] vs. 10 [9, 12] days, U=-2.028, P=0.043). The incidence of surgical complications did not differ significantly between the two groups ( P=0.238). Conclusion:Satisfactory results can be achieved with the five-step procedure for patients with Siewert type II adenocarcinoma of the esophagogastric junction once 25 procedures have been performed.

Objective:To explore the clinical and genetic characteristics of four children with Kabuki syndrome (KS) due to variants of KMT2D gene. Methods:Four children with KS diagnosed at the Children′s Hospital of Shanxi Province between January 2020 and December 2022 were selected as the study subjects. Whole exome sequencing was carried out for the children and their family members. Candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:The KS phenotype scores for the four children were 7, 8, 6, and 6, respectively. Child 2 also presented with a rare solitary kidney malformation. Genetic testing revealed that all children had harbored novel de novo variants of the KMT2D gene, including c. 16472_16473del, c. 858dup, c. 11899C>T, and c. 12844C>T, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were classified as pathogenic. Conclusion:For children showing phenotypes such as distinctive facial features, intellectual disability, developmental delay, cardiac abnormalities, and urinary system anomalies, KS should be considered. Early diagnosis and intervention can be achieved through genetic testing, especially in the presence of KMT2D gene mutations.

Influenza has caused high morbidity and mortality worldwide, seriously endangering human health and life. The continuous mutation of influenza virus has brought new challenges to the prevention and treatment of influenza. Animal models provide convenience for a comprehensive understanding of influenza virus pathogenesis, transmission mechanism, vaccine development, and evaluation of therapeutic effects. The construction and use of animal models of influenza virus infection vary in different studies, and the application of different animal models also has its own characteristics. This article reviewed the current status of the construction and use of various animal models, and summarized the advantages and limitations of animal models in evaluating the efficacy of antibodies, drugs and vaccines, with the aim of providing reference for the selection and optimization of animal models in the future.

Objective:To screen and analyze ferroptosis-related genes (FRG) impacting the prognosis of colorectal adenocarcinoma patients based on bioinformatics.Methods:RNA sequencing data including the clinical information of 545 colorectal adenocarcinoma patients and 602 data sets were downloaded from the Cancer Genome Atlas (TCGA) database. FRG gene sets were downloaded from FerrDb database. FRG expression dataset could be obtained after taking the intersection between FRG gene sets and TCGA database gene sets. Differentially expressed FRG and prognosis-related genes between colorectal adenocarcinoma tissues and the adjacent tissues were screened by using R software, and finally FRG influencing the prognosis of colorectal adenocarcinoma were obtained. According to protein-protein interaction networks, the interaction and the expression association of proteins were analyzed. LASSO regression analysis was used to build a risk model for patients' 5-year overall survival rate. The risk value was calculated for 509 colorectal adenocarcinoma samples in the TCGA database, and then the median risk value was taken as the cut-off value. All patients were divided into the high-risk group (≥ median risk value) and the low-risk group (< median risk value), and the survival curves of the two groups were drawn. The receiver operating characteristic (ROC) curve was drawn for predicting the 5-year overall survival rate of colorectal adenocarcinoma patients in a time-dependent way in TCGA database according to the risk value of FRG prognosis model. Cox proportional risk model was used to make univariate and multivariate survival analysis in order to screen factors affecting the prognosis. The pathway enrichment analysis of prognosis-related FRG of colorectal adenocarcinoma was performed based on gene ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) database.Results:The clinical information of 545 patients and 602 datasets were extracted from the database. A total of differential expressed 199 FRG in colorectal adenocarcinoma and 28 prognosis-related FRG were identified. After taking the intersection, 21 FRG affecting the prognosis of colorectal adenocarcinoma patients were identified. DUOX2, NOX4, NOX1, DDIT3, JDP2, ATP6V1G2, ULK1, ATG3 were probably associated with WIPI1; expressions of NOX4, NOX5, PLIN4 were positively correlated with ATP6V1G2, while the expression of ULK1 was negatively correlated with MAPK1, MYB, FANCD2, ATG3 and ATP5MC3. LASSO regression analysis showed that 15 FRG were finally screened out (ATP5MC3, NOX4, NOX5, ALOX12B, ATG3, WIPI1, MAPK1, MYB, AKR1C1, DDIT3, JDP2, ATP6V1G2, DRD4, SLC2A3, PLIN4), and the risk model was constructed by calculating the risk value, and the risk value = NOX4×0.139-ATP5M3×0.108+NOX5×1.486+ALOX12B×0.475-ATG3×0.030-WIPI1×0.170-MAPK1×0.271-MYB×0.063+AKR1C1×0.021+DDIT3×0.186+JDP2×0.292+ATP6V1G2×0.777+DRD4×0.294+SLC2A3×0.059+PLIN4×0.113. The overall survival of patients in the high-risk group was worse than that in the low-risk group ( P < 0.001). The 5-year overall survival rate was 48.2% in the high-risk group and 76.8% in the low-risk group. Multivariate survival showed that the age and risk value were independent affecting factors of the prognosis. ROC curves revealed that the risk model constructed by using prognosis-related FRG could well predict the 5-year overall survival rate of patients (the area under the curve was 0.728). The differential expressed genes of both groups may be associated with genetic pathways such as extracellular matrix composition, extracellular structure composition and focal adhesion. Conclusions:The prognostic risk model constructed by the screened FRG can better evaluate the prognosis of colorectal adenocarcinoma patients. These FRG are expected to become new candidate biomarkers related to the prognosis of colorectal adenocarcinoma.

Objective:To investigate the relationship between cognitive function and brain event-related potential in patients with lacunar cerebral infarction.Methods:A total of 464 patients with lacunar cerebral infarction admitted to the Department of Neurology, Kailuan General Hospital from 2014 to 2019 were prospectively selected as observation subjects (case group). According to mini-mental state examination (MMSE) score, the patients in the case group were divided into 352 cases of lacunar cerebral infarction with normal cognition and 112 cases of mild cognitive impairment. At the same time, 100 healthy volunteers were selected as the control group. All subjects were assessed by simple intelligent mental state, Zung self-rating anxiety scale, Zung self-rating depression scale and brain event-related potential P3a and P3b. The measurement data of normal distribution adopts one-way ANOVA, the measurement data of non normal distribution adopts Kruskal Wallis H test, and the counting data adopts χ2. Multivariate statistical analysis was performed by unconditional Logistics (stepwise method). Results:The proportions of smokers in control group, lacunar cerebral infarction cognitive normal group and lacunar cerebral infarction mild cognitive impairment group were 20.00% (20/100), 38.07% (134/352) and 46.42% (52/112), respectively. The proportions of drinkers were 18.00% (18/100), 33.24% (117/352), 33.93% (38/112), respectively. The proportions of hypertension were 38.00% (38/100), 58.24% (205/352), 59.82% (67/112), respectively. The proportions of hyperhomocysteinemia were 19.00% (19/100), 34.00% (120/352) and 68.75% (77/112), respectively, and the differences among the three groups were statistically significant ( χ2 values were 15.66, 7.91, 11.86 and 54.57, respectively; P<0.001, 0.019, 0.003, <0.001). The peak latency CZ leads of visual P3b wave group N2 were (271.48±40.65), (285.67±44.08) and (290.57±68.41) ms, respectively. PZ leads were (276.70±50.92), (287.86±43.28) and (312.16±62.75) ms. P3b peak latency FZ leads were (392.67±42.50), (405.82±52.43) and (410.34±64.27) ms. CZ leads were (395.04±42.44), (412.51±55.86) and (433.28±66.32) ms. PZ leads were (398.24±40.93), (411.17±49.48) and (435.78±67.69) ms. N2 amplitude CZ leads were (-3.99±2.81), (-3.60±3.00) and (-2.70±2.37) μV, PZ leads were (-3.18±2.69), (-2.91±2.62) and (-1.87±2.89) μV, respectively. Leads P3b amplitude of FZ were 5.27 (3.27, 7.40), 4.21 (2.31, 6.49) and 3.12 (1.61, 5.08) μV. CZ leads were 4.81 (2.78, 6.71), 4.15 (2.76, 6.16) and 3.51 (1.75, 5.15) μV. PZ leads were 5.17 (3.03, 6.97), 4.40 (2.89, 6.12) and 3.43 (1.52, 5.34) μV. There were statistically significant differences among the 3 groups ( F=3.29, 14.49, 3.95, 11.73, 14.06, 5.66 and 3.57, H=18.23, 10.33,18.25; P=0.027, <0.001, 0.025, <0.001, <0.001, 0.004, 0.042, <0.001, 0.006, <0.001). The peak latency FZ leads of visual P3a wave group N2 were 265.00 (256.00, 286.00), 277.00(260.00,300.00), 282.00(270.00,304.00) ms, respectively. CZ leads weres 274.00(255.00,305.00), 285.00(262.00,329.00), 293.50(270.00,346.00) ms. P3a peak latency FZ leads were (413.83±49.58), (429.83±55.38) and (449.04±54.79) ms, CZ leads were (441.53±61.78), (457.12±69.29) and (460.23±72.24) ms. PZ leads were (430.14±54.53), (462.31±69.2) and (470.02±74.92) ms. N2 amplitude FZ leads were (-6.34±3.13), (-5.72±2.96) and (-4.92±2.05) μV, respectively. Leads P3a amplitude of FZ were 4.00 (2.28, 5.55), 3.15 (2.14, 4.91) and 2.80 (2.19, 4.19) μV. CZ lead were 3.37 (1.98, 4.66), 2.73 (1.70, 3.97) and 2.41 (1.64, 3.45) μV. There were statistically significant differences among the three groups ( H=13.92, 8.65, 9.17, 10.02, F=8.18, 6.33, 10.73, 4.62, P =0.001,0.013,0.010,0.007, <0.001,0.002, <0.001,0.010). Logistic regression analysis showed that alcohol consumption, P3b peak latency and wave amplitude PZ lead, N1 wave amplitude of visual P3a group FZ lead were the influencing factors of MMSE ( OR=0.04, 1.01, 0.76, 1.51, 95% Cl were 0.00-0.30, 1.00-1.03, 0.59-0.97, 1.08-2.10, P=0.002,0.007,0.029,0.016). Conclusion:The peak latency and amplitude of endogenous psychological cognitive potentials N2, P3b and P3a of event-related potentials P3b and P3a in patients with lacunar cerebral infarction were prolonged and decreased. At the same time, with the occurrence of clinical cognitive impairment, the peak latency and amplitude of these cognitive potentials were further prolonged and decreased more significantly. Alcohol consumption, P3b peak latency and PZ lead of visual P3b wave group, and FZ lead of N1 wave of visual P3a wave group were the influencing factors of simple intelligent mental state.

The genus Rosa (Rosaceae family) includes about 200 species spread in the world, and this genus shows unique advantages in medicine and food. To date, several scholars concentrated on compounds belonging to flavonoids, triterpenes, tannins, polysaccharide, phenolic acids, fatty acids, organic acids, carotenoids, and vitamins. Pharmacological effects such as antineoplastic and anti-cancer properties, anti-inflammatory, antioxidant, liver protection, regulate blood sugar, antimicrobial activity, antiviral activity, as well as nervous system protection and cardiovascular protection were wildly reported. This article reviews the chemical constituents, pharmacological effects, applications and safety evaluations of Rosa plants, which provides a reference for the comprehensive utilization of medicine and food resources and gives a scientific basis for the development of medicinal plants of the genus Rosa.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Objective:To compare the safety of adrenal central vein treated at different times in laparoscopic adrenal pheochromocytoma resection through abdominal approach.Methods:A study was conducted on 43 patients with adrenal pheochromocytoma admitted to Xijing Hospital, Air Force Military Medical University from June 2012 to June 2019. The included patients were divided into two groups according to the surgical method: observation group ( n=22) and control group ( n=21). The patients of observation group were ligated the central advenal vein before the tumor was completely isolated, and the patients of control group were ligated the central advenal vein after the tumor was isolated. The changes of blood catecholamine levels before anesthesia, before central adrenal vein ligation, and after tumor resection were compared between the two groups, as well as the differences in operative time, intraoperative blood loss, hospital stay, number of cases with intraoperative blood pressure fluctuations and frequency. Measurement data were expressed as mean±standard deviation ( Mean± SD), comparison between groups was by t-test; comparison of count data between groups was by Chi-square. Results:There was no significant difference in the mean operation time, the mean hospital stay, intraoperative blood loss, number of cases with dramatic blood pressure fluctuations between two groups ( P>0.05). The frequency of severe fluctuation of intraoperative blood pressure in observation group and control group was 19 times and 47 times, respectively, the difference was statistically significant ( P<0.05). There was no significant difference in the blood epinephrine and norepinephrine levels between the two groups before anesthesia and after tumor resection ( P>0.05). However, before ligation of the central vein, the epinephrine concentrations in the observation group and the control group were (572.1±282.1) pg/mL and (935.6±417.5) pg/mL, respectively, the noradrenaline concentrations were (8 347.9±4 103.6) pg/mL and (13 695.7 ±3 205.3) pg/mL, respectively, the difference was statistically significant ( P<0.05). Conclusion:Early ligation of the adrenal central vein can improve the safety of the laparoscopic approach to adrenal pheochromocytoma.