Objective To investigate the protective effect of valeric acid on Doxorubicin-induced myocardial injury in mice.Methods C57BL/6J mice and AC16 cells were randomly divided into control group,injury group,and low-,medium-,and high-dose valeric acid groups.Doxorubicin was used to treat mice and myocardial cells to establish myocardial injury models.Hematoxylin-eosin(HE)staining was used to analyze the pathological changes of myocardial tissue in mice,and enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of myocardial injury markers and inflammatory factors in mice from each group.Cell counting kit was used to detect the viability of myocardial cells in each group,and spectrophotometry was used to detect the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in the serum and myocardial cells in mice from each group.Reactive oxygen species(ROS)fluorescence probe was used to detect the levels of reactive oxygen species in each group,and flow cytometry was used to detect the apoptosis rate of each group.Western blot was used to detect the expression levels of nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase 1(HO-1)proteins in myocardial tissue and myocardial cells of mice from each group.Results Compared with the injury group,the myocardial injury in the low-,medium-,and high-dose valeric acid groups was ameliorated,the levels of myocardial injury markers gradually decreased,the levels of SOD in the body,and the expression levels of Nrf2 and HO-1 proteins gradually increased,and the levels of inflammatory factors,MDA,and apoptosis rate gradually decreased(P<0.05).Compared with myocardial cells in the injury group,the viability of myocardial cells,the levels of SOD,and the expression levels of Nrf2 and HO-1 proteins in the low-,medium-,and high-dose valeric acid groups gradually increased,while the levels of inflammatory factors,MDA,and apoptosis rate gradually decreased(P<0.05).Conclusion Valeric acid can inhibit inflammation and oxidative stress to improve Doxorubicin-induced myocardial injury,which may be related to the activation of Nrf2/HO-1 signaling pathway by valeric acid.

Objective:To evaluate the effects of different doses of sufentanil on the pupillary dilation reflex (PDR) during induction of general anesthesia.Methods:In this randomized controlled study, 124 patients of either sex, aged 18-64 yr, with a body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing surgery with general anesthesia, were divided into 4 groups ( n=31 each) using a random number table method: control group (group C) and different doses of sufentanil groups (S1-S3 groups). Sufentanil 0.2, 0.4 and 0.6 μg/kg were intravenously injected in S1-S3 groups, respectively, and the equal volume of normal saline was injected instead in group C. Tetanic stimulation (50 mA, 50 Hz, 5 s) was applied at 5 min after injection of sufentanil. Pupil diameter was measured and the pupillary dilation value and dilation rate were calculated upon entering the operating room while awake, after loss of consciousness, 5 min after intravenous injection of sufentanil, and at maximal pupil diameter after tetanic stimulation. The presence or absence of PDR, PDR latency and PDR duration were also recorded. Results:The pupillary dilation values and dilation rates decreased progressively from group C through groups S1 to S3 ( P<0.05). Compared to group C, the disappearance rate of PDR was significantly increased, and the latency of PDR was prolonged in groups S2 and S3, and the duration of PDR was significantly shortened in groups S1-S3 ( P<0.05). Compared to group S1, the disappearance rate of PDR was significantly increased, and the latency of PDR was prolonged in S2 and S3 groups ( P<0.05). Conclusions:The inhibitory effect of sufentanil on the PDR during induction of general anesthesia is dose-dependent.

Objective:To evaluate the effects of different doses of sufentanil on the pupillary dilation reflex (PDR) during induction of general anesthesia.Methods:In this randomized controlled study, 124 patients of either sex, aged 18-64 yr, with a body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing surgery with general anesthesia, were divided into 4 groups ( n=31 each) using a random number table method: control group (group C) and different doses of sufentanil groups (S1-S3 groups). Sufentanil 0.2, 0.4 and 0.6 μg/kg were intravenously injected in S1-S3 groups, respectively, and the equal volume of normal saline was injected instead in group C. Tetanic stimulation (50 mA, 50 Hz, 5 s) was applied at 5 min after injection of sufentanil. Pupil diameter was measured and the pupillary dilation value and dilation rate were calculated upon entering the operating room while awake, after loss of consciousness, 5 min after intravenous injection of sufentanil, and at maximal pupil diameter after tetanic stimulation. The presence or absence of PDR, PDR latency and PDR duration were also recorded. Results:The pupillary dilation values and dilation rates decreased progressively from group C through groups S1 to S3 ( P<0.05). Compared to group C, the disappearance rate of PDR was significantly increased, and the latency of PDR was prolonged in groups S2 and S3, and the duration of PDR was significantly shortened in groups S1-S3 ( P<0.05). Compared to group S1, the disappearance rate of PDR was significantly increased, and the latency of PDR was prolonged in S2 and S3 groups ( P<0.05). Conclusions:The inhibitory effect of sufentanil on the PDR during induction of general anesthesia is dose-dependent.

Objective:To investigate the histopathological subtype and clinical characteristics of vascular malformations in the head and neck.Methods:All patients with head and neck vascular malformations referred to Henan Provincial People′s Hospital between January 2021 and December 2023 were collected, and the clinicopathological features were analyzed by SPSS 26.0 statistical software.Results:A total of 675 patients were included, there were 293 male and 382 female patients with a mean onset age of (26.2±21.8）years and a mean diagnosis age of (31.8±20.6）years. Most vascular malformations were located in oral and maxillofacial region (52.1%, 352/675), with an average diameter of (28.0±19.8）mm. Venous malformations were the most common (71.4%, 482/675). There were 230 patients presented with simultaneous phenomenon, and of them the thrombus was most commonly noted (66.5%, 153/230). Venous malformations more frequently occurred in patients who were older than 20 years, extracranial in site, and mostly involved female patients with complications. Combined vascular malformation more frequently occurred in patients who were under 20 years old, extracranial in site, and mostly involved female patients. Capillary malformations more frequently occurred in patients under 20 years old, extracranial in site, and no complications occurred. Lymphatic vessel malformation more frequently occurred in patients who were under 20 years old, extracranial in site, female and with no complications. Arteriovenous malformations were more common in the intracranial and most of them were without any complications. Two cases (2/21) were associated with PIK3CA gene mutation. There were 109 patients with recurrence after initial treatment.Conclusions:Vascular malformations in the head and neck are more commonly found in the extracranial and maxillofacial regions, and venous malformations are the most common type; while arteriovenous malformations are more common in the intracranial site. Appropriate diagnosis is the premise of appropriate treatment.

Objective To investigate the protective effect of valeric acid on Doxorubicin-induced myocardial injury in mice.Methods C57BL/6J mice and AC16 cells were randomly divided into control group,injury group,and low-,medium-,and high-dose valeric acid groups.Doxorubicin was used to treat mice and myocardial cells to establish myocardial injury models.Hematoxylin-eosin(HE)staining was used to analyze the pathological changes of myocardial tissue in mice,and enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of myocardial injury markers and inflammatory factors in mice from each group.Cell counting kit was used to detect the viability of myocardial cells in each group,and spectrophotometry was used to detect the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in the serum and myocardial cells in mice from each group.Reactive oxygen species(ROS)fluorescence probe was used to detect the levels of reactive oxygen species in each group,and flow cytometry was used to detect the apoptosis rate of each group.Western blot was used to detect the expression levels of nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase 1(HO-1)proteins in myocardial tissue and myocardial cells of mice from each group.Results Compared with the injury group,the myocardial injury in the low-,medium-,and high-dose valeric acid groups was ameliorated,the levels of myocardial injury markers gradually decreased,the levels of SOD in the body,and the expression levels of Nrf2 and HO-1 proteins gradually increased,and the levels of inflammatory factors,MDA,and apoptosis rate gradually decreased(P<0.05).Compared with myocardial cells in the injury group,the viability of myocardial cells,the levels of SOD,and the expression levels of Nrf2 and HO-1 proteins in the low-,medium-,and high-dose valeric acid groups gradually increased,while the levels of inflammatory factors,MDA,and apoptosis rate gradually decreased(P<0.05).Conclusion Valeric acid can inhibit inflammation and oxidative stress to improve Doxorubicin-induced myocardial injury,which may be related to the activation of Nrf2/HO-1 signaling pathway by valeric acid.

Objective:To investigate the histopathological subtype and clinical characteristics of vascular malformations in the head and neck.Methods:All patients with head and neck vascular malformations referred to Henan Provincial People′s Hospital between January 2021 and December 2023 were collected, and the clinicopathological features were analyzed by SPSS 26.0 statistical software.Results:A total of 675 patients were included, there were 293 male and 382 female patients with a mean onset age of (26.2±21.8）years and a mean diagnosis age of (31.8±20.6）years. Most vascular malformations were located in oral and maxillofacial region (52.1%, 352/675), with an average diameter of (28.0±19.8）mm. Venous malformations were the most common (71.4%, 482/675). There were 230 patients presented with simultaneous phenomenon, and of them the thrombus was most commonly noted (66.5%, 153/230). Venous malformations more frequently occurred in patients who were older than 20 years, extracranial in site, and mostly involved female patients with complications. Combined vascular malformation more frequently occurred in patients who were under 20 years old, extracranial in site, and mostly involved female patients. Capillary malformations more frequently occurred in patients under 20 years old, extracranial in site, and no complications occurred. Lymphatic vessel malformation more frequently occurred in patients who were under 20 years old, extracranial in site, female and with no complications. Arteriovenous malformations were more common in the intracranial and most of them were without any complications. Two cases (2/21) were associated with PIK3CA gene mutation. There were 109 patients with recurrence after initial treatment.Conclusions:Vascular malformations in the head and neck are more commonly found in the extracranial and maxillofacial regions, and venous malformations are the most common type; while arteriovenous malformations are more common in the intracranial site. Appropriate diagnosis is the premise of appropriate treatment.

Objective To establish a coronavirus(CoV)infection model using human nasal mucosa organoids for testing antiviral drugs and evaluate the feasibility of using human nasal mucosa organoids with viral infection as platforms for viral research and antiviral drug development.Methods Human nasal mucosa organoids were tested for susceptibility to SARS-CoV-2 and HCoV-OC43 pseudoviruses.In a P3 laboratory,nasal mucosa organoids were infected with the original strain of SARS-CoV-2 and 4 variant strains,and the infection conditions were optimized.The viral loads in the culture supernatants were measured at different time points using RT-qPCR,and immunofluorescence assay was employed to localize SARS-CoV-2 nucleocapsid protein to determine the type of the infected cells.In the optimized nasal mucosa viral infection model,the antiviral effects of camostat and bergamot extract(which were known to inhibit SARS-CoV-2)were tested and the underlying molecular mechanisms were explored.Results In the optimized nasal mucosa organoid models infected with SARS-CoV-2 and HCoV-OC43 pseudoviruses,the viral load in the culture supernatants increased significantly during the period of 2 to 24 h following the infection,which confirmed infection of the organoids by both of the pseudoviruses.The nasal mucosa organoids could be stably infected by the original SARS-CoV-2 strain and its 4 variant strains,validating successful establishment of the viral infection model,in which both camostat and bergamot extract exhibited dose-dependent antiviral effects.Conclusions Human nasal mucosa organoids with SARS-CoV-2 infection can serve as platforms for screening and testing antiviral drugs,particularly those intended for nasal administration.

Objective To establish a coronavirus(CoV)infection model using human nasal mucosa organoids for testing antiviral drugs and evaluate the feasibility of using human nasal mucosa organoids with viral infection as platforms for viral research and antiviral drug development.Methods Human nasal mucosa organoids were tested for susceptibility to SARS-CoV-2 and HCoV-OC43 pseudoviruses.In a P3 laboratory,nasal mucosa organoids were infected with the original strain of SARS-CoV-2 and 4 variant strains,and the infection conditions were optimized.The viral loads in the culture supernatants were measured at different time points using RT-qPCR,and immunofluorescence assay was employed to localize SARS-CoV-2 nucleocapsid protein to determine the type of the infected cells.In the optimized nasal mucosa viral infection model,the antiviral effects of camostat and bergamot extract(which were known to inhibit SARS-CoV-2)were tested and the underlying molecular mechanisms were explored.Results In the optimized nasal mucosa organoid models infected with SARS-CoV-2 and HCoV-OC43 pseudoviruses,the viral load in the culture supernatants increased significantly during the period of 2 to 24 h following the infection,which confirmed infection of the organoids by both of the pseudoviruses.The nasal mucosa organoids could be stably infected by the original SARS-CoV-2 strain and its 4 variant strains,validating successful establishment of the viral infection model,in which both camostat and bergamot extract exhibited dose-dependent antiviral effects.Conclusions Human nasal mucosa organoids with SARS-CoV-2 infection can serve as platforms for screening and testing antiviral drugs,particularly those intended for nasal administration.

Objective:To investigate the endoscopic combined serological diagnosis strategy for G1 and G2 gastric neuroendocrine neoplasms (G-NENs), and to evaluate the safety, short-term, and long-term efficacy of two endoscopic treatment procedures: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).Methods:This study retrospectively analyzed the clinical data of 100 consecutive patients with G-NENs who were hospitalized at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2011 to October 2023. These patients underwent endoscopic treatment, and propensity score matching (PSM) was used to compare clinicopathological characteristics, as well as short-term and long-term efficacy of lesions in the EMR group and ESD group before and after treatment.Results:Among the 100 patients with G-NENs, the median age was 54 years old. Before surgery, 29 cases underwent endoscopic combined serological examination, and 24 of them (82.2%) had abnormally elevated plasma chromogranin A. The combined diagnostic strategy for autoimmune atrophic gastritis (AIG) achieved a diagnostic accuracy of 100%(22/22). A total of 235 G-NEN lesions were included, with 84 in the ESD group and 151 in the EMR group. The median size of the lesions in the ESD group (5.0 mm) was significantly larger than that in the EMR group (2.0 mm, P＜0.001). Additionally, the ESD group had significantly more lesions with pathological grade G2[23.8%(20/84) vs. 1.3%(2/151), P＜0.001], infiltration depth reaching the submucosal layer [78.6%(66/84) vs. 51.0%(77/151), P＜0.001], and more T2 stage compared to the EMR group[15.5%(13/84) vs. 0.7%(1/151), P＜0.001]. After PSM, 49 pairs of lesions were successfully matched between the two groups. Following PSM, there were no significant differences in the en bloc resection rate [100.0%(49/49) vs. 100.0%(49/49)], complete resection rate [93.9%(46/49) vs. 100.0%(49/49)], and complication rate [0(0/49) vs. 4.1%(2/49)] between the two groups. During the follow-up period, no recurrence or distant metastasis was observed in any of the lesions in both groups. Conclusions:The combination of endoscopy and serology diagnostic strategy has the potential to enhance the accuracy of diagnosing G1 and G2 stage G-NENs and their background mucosa. Endoscopic resection surgery (EMR, ESD) is a proven and safe treatment approach for G1 and G2 stage G-NENs.

Objectives:To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions.Methods:Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set ( n=284) and a validation set ( n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training ( n=243), validation ( n=105), and test ( n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results:We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression ( P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions:Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.