ABSTRACT
Mucosal vaccines that stimulate both mucosal and systemic immune responses are desirable, as they could prevent the invading pathogens at their initial infection sites in a convenient and user-friendly way. Nanovaccines are receiving increasing attention for mucosal vaccination due to their merits in overcoming mucosal immune barriers and in enhancing immunogenicity of the encapsulated antigens. Herein, we summarized several nanovaccine strategies that have been reported for enhancing mucosal immune responses, including designing nanovaccines that have superior mucoadhesion and mucus penetration capacity, designing nanovaccines with better targeting efficiency to M cells or antigen-presenting cells, and co-delivering adjuvants by using nanovaccines. The reported applications of mucosal nanovaccines were also briefly discussed, including prevention of infectious diseases, and treatment of tumors and autoimmune diseases. Future research progresses in mucosal nanovaccines may promote the clinical translation and application of mucosal vaccines.
ABSTRACT
Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.
ABSTRACT
Objective:To investigate the application value of stereotactic digital naviga-tion system assisted three-dimensional (3D) laparoscopic total mesorectal excision (TME) for rectal cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of a healthy volunteer recruited by the Second Affiliated Hospital of Army Medical University and 3 patients who underwent stereotactic digital navigation system assisted 3D laparoscopic TME for rectal cancer in the Second Affiliated Hospital of Army Medical University from May to September 2019 were collected. The healthy volunteer was male, aged 25 years. Of the 3 rectal cancer patients, there were 2 males and 1 female, with the age of 48 years, 63 years and 67 years, respectively. Ten special patches were placed at the anterior superior iliac spine, pubic tubercle and pubic symphysis of the volunteer's bilateral inguen as skin reference points in intraoperative localization and system registration. On the day of operation, patients were placed 10 special patches as skin reference points according to the test results of the volunteer and were completed the enhanced scan of totally abdominal computed tomography examination. Seven fixed anatomical markers in the abdominal cavity of the patients, including abdominal aortic bifurcation, sacrum scapula, bilateral anterior superior iliac spine, bilateral intersection of ureter and iliac artery and median point of peritoneal reflection, were selected for verifying the accuracy of the correspondence between the instrument tip and the system image. Patients underwent 3D laparoscopic TME for rectal cancer assisted by stereotactic digital navigation system. Observation indicators: (1) test results; (2) surgical situations; (3) accuracy of stereotactic digital navigation system. Measurement data with normal distribution were represented as Mean± SD. Results:(1) Test results. The 10 skin reference points of the volunteer were successfully registered in the stereotactic digital navigation system, with the registration error of 2.8 mm. (2) Surgical situations. All the 3 patients underwent stereo-tactic digital navigation system assisted 3D laparoscopic TME for rectal cancer successfully. The operation time of the 3 patients were 193 minutes, 175 minutes, 210 minutes, respectively, in which the set time of the stereotactic digital navigation system were 34 minutes, 25 minutes, 45 minutes, respectively. The volume of intraoperative blood loss of the 3 patients were 60 mL, 30 mL, 80 mL, respectively. Results of postoperative pathological examination showed 3 patients with adenocar-cinoma, including 1 case with mucinous adenocarcinoma. The tumor diameter and the numbers of lymph nodes dissected of the 3 patients were 2.3 cm, 1.5 cm, 4.0 cm and 12, 12, 13, respectively. No patient had lymph node metastasis. The 3 patients in preoperative clinical TNM stage cT3bN0M0, stage cT4aN1M0, stage cT3bN1M0 were in yield pathological TNM stage ypT1N0M0, stage ypT4aN0M0, stage ypT2N0M0 after neoaduvant chemotherapy, respectively. No patient had complication, and the duration of postoperative hospital of the 3 patients was 7 days, 6 days, 7 days, respectively. (3) Accuracy of stereotactic digital navigation system. The registration errors of the skin reference points were 2.8 mm, 2.6 mm, 2.9 mm and the accuracy errors of the abdominal cavity reference points were (2.5±0.4)mm, (2.3±0.7)mm, (2.6±0.6)mm for the 3 patients.Conclusion:The stereotactic digital navigation system assisted 3D laparoscopic TME for rectal cancer is safe and feasible.
ABSTRACT
Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.
ABSTRACT
Colorectal cancer is the fourth most malignant tumors in China, among which the left hemicolon cancer accounts for about 5%?6%. Due to the complex anatomy around the left hemicolon, being adjacent to the pancreas, spleen, kidney, ureter and other important organs, its vascular and nerve distribution is variably distributed, leading difficulties in laparoscopic radical surgery for left hemicolon cancer. In surgical practice, the 4K laparoscopic system has shown its features of high-definition amplification, good color reproduction, and clear anatomy, etc. However, there is still no clear consensus on its application in the radical resection for the left hemicolon cancer. The authors summarize clinical practice, explore the technique key points of 4K laparoscopic D 3 resection with complete mesocolic excision for the left hemicolon cancer.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the feasibility, safety, and preliminary technical experience of single incision plus one port laparoscopic total gastrectomy combined with π-shaped esophagojejunal anastomosis (SILT-π) in the surgical treatment of gastric cancer.</p><p><b>METHODS</b>Clinical data of 5 gastric cancer patients undergoing SILT-π operation at the Department of General Surgery, The Second Affiliated Hospital of the Army Medical University from August to October 2017 were retrospectively analyzed. A 2.5-3.0 cm incision around the umbilicus was made for placing the gloveport as the passage for the lens, and the instruments of the surgeon and the assistant. Another operative port was placed in the left upper quadrant with a 12-mm Trocar for the passage of the energy device, the endoscopic cutting closure, as well as the postoperative drainage tube. A D2 lymph node (LNs) dissection was regularly conducted. After the abdominal esophagus was routinely mobilized, a side-to-side esophagus-jejunum anastomosis was made through a gastric pre-pulling esophagojejunal π-shaped anastomosis. The transection was then performed with a ligation on the cardia (or esophagus above the upper margin of the tumor) using a sterilized hemp rope in order to better expose the abdominal esophagus. Throughout the course of reconstruction, the ligature rope was held by the assistant to hold down the esophagus to allow easier esophagojejunal anastomosis. A hole was then made on the posterior wall of the esophagus, between 2 cm and 3 cm above the ligature rope, and another hole was made at the anti-mesenteric border of the jejunum 40 cm distal to the Treitz ligament. A side-to-side esophagojejunal π-shaped anastomosis was performed through two holes. An entry hole was formed after the anastomosis. After checking the anastomosis, this entry hole was closed through an intestinal mesenteric hole pre-made on its opposite side. The resected esophagus and stomach, together with the afferent loop jejunum, were simultaneously transected above the level of the entry hole by a stapler from the Trocar of the left upper abdominal quadrant. After the gloveport was closed, a side-to-side jejunojejunostomy anastomosis applied with another two staples was performed between the afferent loop stump and the roux limb 30 cm below the esophagojejunal anastomosis.</p><p><b>RESULTS</b>These five patients were all male, and aged (56.8±8.2) years with preoperative clinical stage cT2-4N0-2M0. All the 5 patients underwent SILT-π operation successfully. The average length of surgical incision was (2.9±0.2) cm. The average operation time was (396.0±36.1) minutes. The intraoperative blood loss was (140.0±66.7) ml. Postoperative pathology showed proximal and distal margins were (2.6±1.1) cm and (8.7±2.5) cm apart respectively, and the average number of retrieved lymph node was 25.8±7.2. Perioperative management was based on enhanced recovery following surgical (ERAS) principles. The average time to the first flatus was (2.6±0.5) days, and the average time to defecation was (3.6±0.5) days. The pain score on postoperative day 1 was 1-2, and the average postoperative hospital stay was (7.0±0.7) days. No perioperative complications occurred.</p><p><b>CONCLUSIONS</b>SILT-π procedure is safe and feasible for patients with gastric cancer, and has positive short-term outcomes, satisfactory cosmetic abdominal incision, light postoperative abdominal pain and rapid postoperative recovery. Preliminary observations show that SILT-π procedure has good potential for clinical application in future.</p>
Subject(s)
Aged , Humans , Male , Middle Aged , Anastomosis, Surgical , Esophagus , General Surgery , Gastrectomy , Methods , Jejunum , General Surgery , Laparoscopy , Retrospective Studies , Stomach Neoplasms , General SurgeryABSTRACT
Objective To determine the optimum dose of Oxycodone for anesthesia induction in patients undergoing laparoscopic cholecystectomy. Methods Ninety patients, ASA Ⅰ or Ⅱ , scheduled for elective LC, were randomly divided into 3 groups using random number table (O 1~O 3 groups, n = 30 each). Anesthesia was induced with iv Propofol 1.00~2.00 mg/kg, Oxycodone 0.20 mg/kg, 0.3 mg/kg and 0.4 mg/kg (O 1~O 3 groups, respectively), and Vecuronium 0.10 mg/kg. Before anesthesia induction ( T0 ), 1 min after Laryngeal Mask intubating ( T1 ), the instant of pneumoperitoneum ( T2 ), separation of the gallbladder ( T3 ), wake up immediately ( T4 ), leaving the recovery room ( T5 ), the heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded. At T4, leaving the recovery room ( T5 ), 4 hours after the operation ( T6 ), 8 hours after operation (T7), the numeric pain rating scale (NRS) were recorded. The overall amount of remifentanil and Oxycodone were record. The wake up time, additional analgetic cases and the adverse reactions were recorded. Results The average HR, SBP and DBP fluctuations in the O 2 and O 3 groups were not more than 20.00% of the basal values. There was no significant difference in wake up time between the three groups. There were 22 cases of patients, the NRS> 4, in O1 group requires additional analgesics after they wake up, more than O 2 and O 3 group (7, 3 respectively, P < 0.05). The overall Oxycodone consumption of the three groups were O1: (18.93 ± 4.34) mg (0.90~2.60 mg),O2: (25.50 ± 4.49) mg (1.40~3.00 mg), O3: (26.10 ± 4.55) mg (1.80~3.40 mg) (F = 23.79, P = 0.000). There was no significant difference in adverse reactions between the three groups, but one patient had respiratory depression in O3 group. Conclusion The optimum dose of Oxycodone for anesthesia inducing in laparoscopic cholecystectomy were 0.30 mg/kg.
ABSTRACT
The purpose of the present study was to examine the effects of oxidative stress on ventricular arrhythmias in rabbits with adriamycin-induced cardiomyopathy and the relationship between oxidative stress and ventricular arrhythmia. Forty Japanese white rabbits were randomly divided into four groups (n=10 in each): control group, metoprolol (a selective β1 receptor blocker) group, carvedilol (a nonselective β blocker/α-1 blocker) group and adriamycin group. Models of adriamycin-induced cardiomyopathy were established by intravenously injecting adriamycin hydrochloride (1 mg/kg) to rabbits via the auri-edge vein twice a week for 8 weeks in the adriamycin, metoprolol and carvedilol groups. Rabbits in the control group were given equal volume of saline through the auri-edge vein. Rabbits in the metoprolol and carvedilol groups were then intragastrically administrated metoprolol (5 mg/kg/d) and carvedilol (5 mg/kg/d) respectively for 2 months, while those in the adriamycin and control groups were treated with equal volume of saline in the same manner as in the metroprolol and carvedilol groups. Left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), malondialdehyde (MAD) and superoxide dismutase (SOD) were detected. The left ventricular wedge preparations were perfused with Tyrode's solution. The transmural electrocardiogram, transmural action potentials from epicardium (Epi) and endocardium (Endo), transmural repolarization dispersion (TDR) were recorded, and the incidences of triggered activity and ventricular arrhythmias were obtained at rapid cycle lengths. The results showed that TDR and the serum MDA and NT-proBNP levels were increased, and LVEF and the serum SOD level decreased in the adriamycin group compared with the control group. The incidences of triggered activity and ventricular arrhythmia were significantly higher in the adriamycin group than those in the control group (P<0.05). In the carvedilol group as compared with the adriamycin group, the serum SOD level and the LVEF were substantially increased; the TDR, and the serum MDA and NT-proBNP levels were significantly decreased; the incidences of triggered activity and ventricular arrhythmia were obviously reduced (P<0.05). There were no significant differences in the levels of MDA and SOD, LVEF, TDR and the incidences of triggered activity and ventricular arrhythmia between the adriamycin group and the metoprolol group. It was concluded that carvedilol may inhibit triggered activity and ventricular arrhythmias in rabbit with adriamycin-induced cardiomyopathy, which is related to the decrease in oxygen free radials.
Subject(s)
Animals , Male , Rabbits , Anti-Arrhythmia Agents , Antibiotics, Antineoplastic , Carbazoles , Cardiomyopathies , Doxorubicin , Heart Rate , Metoprolol , Oxidative Stress , Propanolamines , Treatment Outcome , Ventricular FibrillationABSTRACT
The purpose of the present study was to examine the effects of oxidative stress on ventricular arrhythmias in rabbits with adriamycin-induced cardiomyopathy and the relationship between oxidative stress and ventricular arrhythmia. Forty Japanese white rabbits were randomly divided into four groups (n=10 in each): control group, metoprolol (a selective β1 receptor blocker) group, carvedilol (a nonselective β blocker/α-1 blocker) group and adriamycin group. Models of adriamycin-induced cardiomyopathy were established by intravenously injecting adriamycin hydrochloride (1 mg/kg) to rabbits via the auri-edge vein twice a week for 8 weeks in the adriamycin, metoprolol and carvedilol groups. Rabbits in the control group were given equal volume of saline through the auri-edge vein. Rabbits in the metoprolol and carvedilol groups were then intragastrically administrated metoprolol (5 mg/kg/d) and carvedilol (5 mg/kg/d) respectively for 2 months, while those in the adriamycin and control groups were treated with equal volume of saline in the same manner as in the metroprolol and carvedilol groups. Left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), malondialdehyde (MAD) and superoxide dismutase (SOD) were detected. The left ventricular wedge preparations were perfused with Tyrode's solution. The transmural electrocardiogram, transmural action potentials from epicardium (Epi) and endocardium (Endo), transmural repolarization dispersion (TDR) were recorded, and the incidences of triggered activity and ventricular arrhythmias were obtained at rapid cycle lengths. The results showed that TDR and the serum MDA and NT-proBNP levels were increased, and LVEF and the serum SOD level decreased in the adriamycin group compared with the control group. The incidences of triggered activity and ventricular arrhythmia were significantly higher in the adriamycin group than those in the control group (P<0.05). In the carvedilol group as compared with the adriamycin group, the serum SOD level and the LVEF were substantially increased; the TDR, and the serum MDA and NT-proBNP levels were significantly decreased; the incidences of triggered activity and ventricular arrhythmia were obviously reduced (P<0.05). There were no significant differences in the levels of MDA and SOD, LVEF, TDR and the incidences of triggered activity and ventricular arrhythmia between the adriamycin group and the metoprolol group. It was concluded that carvedilol may inhibit triggered activity and ventricular arrhythmias in rabbit with adriamycin-induced cardiomyopathy, which is related to the decrease in oxygen free radials.
ABSTRACT
In order to investigate the influence of silencing soluble epoxide hydrolase (sEH) with double-stranded small interfering RNA (siRNA) on cardiomyocytes apoptosis induced by doxorubicin (DOX), two plasmids containing siRNA sequences specific to sEH were constructed and transfected into the primary cultured cardiomyocytes by using FuGENE HD transfection agents. The mRNA and protein expression levels of sEH were detected by semiquantitative RT-PCR and Western blotting respectively, and the plasmids that silenced sEH most significantly were selected, and renamed EH-R. The plasmids carrying a nonspecific siRNA coding sequence (PCN) served as the negative control. Cardiomyocytes were divided into four groups: control group, DOX group, PCN+DOX group, and EH-R+DOX group. Apoptosis of cardiomyocytes was induced by DOX at a concentration of 1 μmol/L. Apoptosis rate of cardiomyocytes was determined by flow cytometery. The protein expression levels of Bcl-2 and Bax were detected by Western blotting. The results showed that the expression of sEH was down-regulated by EH-R plasmid. The expression levels of sEH mRNA and protein in the EH-R+DOX group were significantly decreased as compared with other groups (P<0.01). As compared with the control group, the apoptosis rate of cardiomyocytes in three DOX-treated groups was obviously increased, the expression levels of Bax increased, and those of Bcl-2 decreased (P<0.01). However, the expression levels of Bax were decreased, those of Bcl-2 increased and the apoptosis rate of cardiomyocytes obviously decreased in EH-R+DOX group when compared with those in the DOX group and the PCN+DOX group (P<0.01 for each). It was concluded that the recombinant plasmids could be successfully constructed, and transfected into the primary cultured cardiomyocytes. They could ameliorate the DOX-induced cardiomyocytes apoptosis by selectively inhibiting the expression of sEH with RNAi and increasing the expression of Bcl-2.