The compound (E)-1-(4-(3-(5-chloro-6-oxo-3,6-dihydropyridin-1(2H)-yl)-3-oxo-propyl-1-ene-1-yl) phenyl)-3-(4-fluorophenyl) urea (C12), a novel derivative of piperlongumine previously synthesized by our research group, was investigated in this study to examine its effects on human non-small cell lung cancer cell line H1299 in vitro and elucidate its potential mechanism of action. The impact of C12 on the proliferation, migration, and invasion abilities of H1299 cells were assessed using methyl thiazolyl tetrazolium (MTT) assay, wound healing assay, cloning formation assay, and Transwell assay. Flow cytometry was employed to evaluate the influence of C12 on cell cycle progression, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and apoptosis induction in H1299 cells. Western blot analysis was conducted to investigate the expression levels of p21, Cyclin B1, CDK1, Bax, Bcl-2, JNK, p-JNK, Erk1/2, p-Erk1/2, p38 and p-p38 proteins for exploring the anti-tumor mechanism underlying C12's actions. The results demonstrated that C12 exerted inhibitory effects on the proliferation, migration, and invasion capacities of H1299 cells in a time-dependent and concentration-dependent manner. Moreover, C12 induced G2/M phase arrest in the cell cycle, reduced MMP levels, elevated ROS production, and triggered apoptotic processes. Flow cytometry analysis revealed that C12 downregulated Cyclin B1 and CDK1 protein expressions, resulting in G2/M phase arrest. C12 also upregulated Bax/Bcl-2 ratio, promoting apoptosis. Furthermore, C12 activated MAPK signaling pathway by enhancing phosphorylation levels of JNK, Erk1/2, and p38 proteins. In conclusion, C12 significantly suppressed proliferation, migration, and invasion capabilities while inducing cell cycle arrest and apoptosis in H1299 cells. These effects may be attributed to activation of the MAPK signaling pathway.

Objective: To investigate the clinical value of observing perioperative changes of myeloperoxidase (MPO) and neutrophil elastase (NE) in coronary artery circulation in patients underwent valve replacement surgery. Methods: This perspective cohort study was performed in patients who underwent valvular surgery in Nanjing Drum Tower Hospital and Fuwai Hospital from June 2021 to June 2022. Patients were divided into perioperative myocardial injury group and age-, sex- and type of cardiac procedure-matched non-perioperative myocardial injury control group in the ratio of 1∶1. Perioperative myocardial injury was defined as cardiac troponin T (cTnT)>0.8 μg/L on the first postoperative day (POD), and the cTnT level on the second POD increased by more than 10% compared with the cTnT level on the first POD. During the operation, blood samples were collected from the coronary sinus before clamping ascending aorta, and within 5 minutes after de-clamping ascending aorta. Then, the levels of MPO and NE on coronary sinus were continuously measured. The death, severe ventricular arrhythmia, pneumonia, re-intubation, repeat cardiac surgery, extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), continuous renal replacement therapy (CRRT), mechanical ventilation time and the duration of intensive care unit (ICU) were recorded. The levels of MPO and NE and the incidence of clinical outcomes were compared between the myocardial injury group and the control group. The independent risk factors of myocardial injury were analyzed by multivariate logistic regression. Results: A total of 130 patients were enrolled, aged (60.6±7.6) years old, with 59 males (45.4%). There were 65 patients in the myocardial injury group and 65 patients in the control group. During hospitalization, there was no death, ECMO, IABP and CRRT cases in both groups. Compared with the control group, the incidence of severe ventricular arrhythmia (13.8%(9/65) vs. 3.1%(2/65), P=0.03), pneumonia (20.0%(13/65) vs. 3.1%(2/65), P=0.03), re-intubation (6.2%(4/65) vs. 0, P=0.04) was significantly higher in myocardial injury group. The mechanical ventilation time (16.8(10.7, 101.7) h vs. 7.5(4.7, 15.1) h, P<0.01), and the duration of ICU (3.7(2.7, 18.9) vs. 2.7(1.8, 6.9)d, P<0.01) were significantly longer in myocardial injury group compared with the control group. There was no significant difference in the levels of MPO and NE in coronary sinus blood between the two groups before aortic clamping (all P>0.05). However, MPO ((551.3±124.2) μg/L vs. (447.2±135.9) μg/L, P<0.01) and NE ((417.0±83.1)μg/L vs. (341.0±68.3)μg/L, P<0.01) after 5 min aortic de-clamping were significantly higher in myocardial injury group than in the control group. Multivariate logistic regression analysis showed that the levels of NE (OR=1.02, 95%CI: 1.01-1.02, P<0.01), MPO (OR=1.00, 95%CI: 1.00-1.01, P=0.02) and mechanical ventilation time (OR=1.03, 95%CI: 1.01-1.06, P=0.02) were independent risk factors of myocardial injury in patients after surgical valvular replacement. Conclusion: Perioperative myocardial injury is related poor clinical outcomes, perioperative NE and MPO in coronary artery circulation are independent risk factors of perioperative myocardial injury in patients undergoing valve replacement surgery.
Aged ; Humans ; Male ; Middle Aged ; Cohort Studies ; Coronary Circulation ; Leukocyte Elastase ; Peroxidase ; Prognosis ; Retrospective Studies ; Female

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Humans ; Child ; Neurofibromatosis 1/drug therapy* ; Benzimidazoles/therapeutic use*

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ² test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.
Colectomy ; Colonic Neoplasms/surgery* ; Female ; Humans ; Laparoscopy ; Male ; Prognosis ; Propensity Score ; Retrospective Studies ; Robotic Surgical Procedures ; Treatment Outcome

Telemedicine, which integrates medicine, communication, engineering, information and other disciplines, is a hot emerging cross field in recent years. With the development of telecommunication technology and surgical robot, telesurgery is regarded as the "crown pearl" in telemedicine and has attracted more and more attention. As an extension of traditional surgery, telesurgery greatly extends the connotation and concept of surgery and embodies the great leap forward development of surgical technology. Despite the current limitations such as network delay, transparency of remote robot operation and team construction of surgeons, telesurgery has still formed a variety of innovative application scenarios and achieved rapid development in China in recent years. In view of the uneven distribution of medical resources in China and the epidemic of COVID-19 in the world, this paper puts forward the possible problems and solutions in the development of telesurgery, and looks forward to the feasibility of telesurgery technology in process of shifting the focus of medical and health care down to the community level, channeling resources accordingly.
COVID-19 ; Delivery of Health Care ; Humans ; Robotic Surgical Procedures ; Robotics ; Telemedicine

Objective: To summarize the clinical experience of expanded internal mammary artery perforator (IMAP) flap combined with vascular supercharge in reconstruction of faciocervical scar. Methods: The retrospective observational study was conducted. From September 2012 to May 2021, 23 patients with postburn or posttraumatic faciocervical scars who met the inclusion criteria were admitted to Shanghai Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine, including 18 males and 5 females, aged from 11 to 58 years, all of whom were reconstructed with expanded IMAP flaps. At the first stage, one or two skin and soft tissue expander (s) with appropriate rated capacity were implanted in the anterior chest area according to the location and size of the scars. The IMAP, thoracic branch of supraclavicular artery, and lateral thoracic artery were preserved during the operation. The skin and soft tissue expanders were inflated with normal saline after the operation. The flaps were transferred during the second stage. The dominant IMAP was determined preoperatively using color Doppler ultrasound (CDU) blood flow detector. The faciocervical scars were removed, forming wounds with areas of 9 cm×7 cm-28 cm×12 cm, and the perforators of superficial temporal artery and vein or facial artery and vein were preserved during the operation. The flaps were designed according to the area and size of the wounds after scar resection with the dominant IMAP as the pedicle. Single-pedicle IMAP flaps were used to repair small and medium-sized wounds. For larger defects, the blood perfusion areas of vessels in the anterior chest were evaluated by indocyanine green angiography (ICGA). In situations where the IMAP was insufficient to nourish the entire flap, double-pedicle flaps were designed by using the thoracic branch of supraclavicular artery or lateral thoracic artery for supercharging. Pedicled or free flap transfer was selected according to the distance between the donor areas and recipient areas. After transplantation of flaps, ICGA was conducted again to evaluate blood perfusion of the flaps. The donor sites of flaps were all closed by suturing directly. Statistics were recorded, including the number, rated capacity, normal saline injection volume, and expansion period of skin and soft tissue expanders, the location of the dominant IMAP, the total number of the flaps used, the number of flaps with different types of vascular pedicles, the flap area, the flap survival after the second stage surgery, the occurrence of common complications in the donor and recipient areas, and the condition of follow-up. Results: Totally 25 skin and soft tissue expanders were used in this group of patients, with rated capacity of 200-500 mL, normal saline injection volume of 855-2 055 mL, and expansion period of 4-16 months. The dominant IMAP was detected in the second intercostal space (20 sides) or the third intercostal space (5 sides) before surgery. A total of 25 expanded flaps were excised, including 2 pedicled IMAP flaps, 11 free IMAP flaps, 4 pedicled thoracic branch of supraclavicular artery+free IMAP flaps, and 8 free IMAP+lateral thoracic artery flaps, with flap areas of 10 cm×8 cm-30 cm×14 cm. After the second stage surgery, tip necrosis of flaps in three patients occurred, which healed after routine dressing changes; one patient developed arterial embolism and local torsion on the vascular pedicle at the anastomosis of IMAP and facial artery, and the blood supply recovered after thrombectomy and vascular re-anastomosis. Fourteen patients underwent flap thinning surgery in 1 month to 6 months after the second stage surgery. The follow-up for 4 months to 9 years showed that all patients had improved appearances of flaps and functions of face and neck and linear scar in the donor sites of flaps, and one female patient had obvious nipple displacement and bilateral breast asymmetry. Conclusions: The expanded IMAP flap is matched in color and texture with that of the face and neck, and its incision causes little damage to the chest donor sites. When combined with vascular supercharge, a double-pedicle flap can be designed flexibly to further enhance the blood supply and expand the flap incision area, which is a good choice for reconstruction of large faciocervical scar.
China ; Cicatrix/surgery* ; Female ; Humans ; Male ; Mammary Arteries/surgery* ; Perforator Flap ; Reconstructive Surgical Procedures ; Saline Solution ; Skin Transplantation ; Soft Tissue Injuries/surgery* ; Surgical Wound ; Treatment Outcome

Objective: To investigate the effects of compound analgesia on ultra-pulsed fractional carbon dioxide laser (UFCL) treatment of post-burn hypertrophic s in children. Methods: A prospective randomized controlled study was conducted. From April 2018 to March 2020, 169 pediatric patients with post-burn hypertrophic s admitted to the First Affiliated Hospital of Air Force Medical University were randomly divided into general anesthesia alone group (39 cases, 19 males and 20 females, aged 35 (21, 48) months), general anesthesia+lidocaine group (41 cases, 23 males and 18 females, aged 42 (22, 68) months), general anesthesia+ibuprofen suppository group (41 cases, 25 males and 16 females, aged 38 (26, 52) months), and three-drug combination group with general anesthesia + lidocaine+ibuprofen suppository (48 cases, 25 males and 23 females, aged 42 (25, 60) months), and the pediatric patients in each group were treated with corresponding analgesic regimens when UFCL was used to treat s, and the pediatric patients were given comprehensive care throughout the treatment process. The pain degree of pediatric patients scar was evaluated by facial expression,legs,activity,cry,and consolability (FLACC) of children's pain behavior scale at 0 (immediately), 1, 2, and 4 h after awakening from the first anesthesia, respectively. At 4 h after awakening from the first anesthesia of postoperative pain assessment, the self-made analgesia satisfaction questionnaire was used to evaluate the satisfaction for the analgesic effect of the pediatric patients or their families, and the satisfaction rate was calculated. Within 2 h after the first operation, the occurrences of adverse reactions of the pediatric patients, such as nausea and vomiting, headache, dizziness, drowsiness, etc, were observed and recorded. Before the first treatment and 1 month after the last treatment, the Vancouver scar scale (VSS) was used to evaluate the pediatric patients scar, and the difference value between the two was calculated. Data were statistically analyzed with least significant difference test, Kruskal-Wallis H test, chi-square test and Fisher's exact probability test. Results: At 0 h after awakening from the first anesthesia, the FLACC scores of pediatric patients in general anesthesia+lidocaine group, general anesthesia+ibuprofen suppository group and three-drug combination group were significantly lower than those in general anesthesia alone group (P<0.01). The FLACC scores of the pediatric patients in anesthesia+ibuprofen suppository group and three-drug combination group were significantly lower than that in general anesthesia+lidocaine group (P<0.01), and the FLACC score of the pediatric patients in three-drug combination group was significantly lower than that in general anesthesia+ibuprofen suppository group (P<0.01). At 1 and 2 h after awakening from the first anesthesia, the FLACC scores of pediatric patients in general anesthesia+ibuprofen suppository group and three-drug combination group were both significantly lower than those in general anesthesia alone group and general anesthesia+lidocaine group (P<0.01), and the FLACC score of the pediatric patients in three-drug combination group was significantly lower than that in general anesthesia+ibuprofen suppository group (P<0.01). At 4 h after awakening from the first anesthesia, the FLACC scores of the pediatric patients in general anesthesia+ibuprofen suppository group and three-drug combination group were significantly lower than those in general anesthesia alone group and general anesthesia+lidocaine group (P<0.01). At 4 h after awakening from the first anesthesia, the satisfactions rate with the analgesic effect in the four groups of pediatric patients or their families were 79.49% (31/39), 85.37% (35/41), 87.80% (36/41), and 97.92% (47/48), respectively. The satisfaction rate of the pediatric patients in three-drug combination group was significantly higher than those in general anesthesia alone group, general anesthesia+lidocaine group, general anesthesia+ibuprofen suppository group. Within 2 h after the first operation, there was no significant difference in the overall comparison of adverse reactions such as nausea and vomiting, headache, dizziness, and drowsiness of pediatric patients among the 4 groups (P>0.05). The VSS scores of pediatric patients before the first treatment, 1 month after the last treatment, and and the difference value between the two in the 4 groups were not significantly different (P>0.05). Conclusions: Three-drug combination for analgesia has a good effect in the treatment of hypertrophic scars after burn in pediatric patients with UFCL. Pediatric patients or their families are highly satisfied with the effect, and the treatment effect and incidence of adverse reactions are similar to other analgesic regimens, so it is recommended to be promoted in clinical practice.
Analgesia ; Analgesics ; Child ; Cicatrix, Hypertrophic/pathology* ; Dizziness/drug therapy* ; Female ; Headache/drug therapy* ; Humans ; Ibuprofen/therapeutic use* ; Lasers, Gas/therapeutic use* ; Lidocaine ; Male ; Nausea/drug therapy* ; Pain/drug therapy* ; Prospective Studies ; Treatment Outcome ; Vomiting/drug therapy*

OBJECTIVE: To investigate the effects of CACNA1H gene knockout (KO) on autistic-like behaviors and the morphology of hippocampal neurons in mice. METHODS: In the study, 25 CACNA1H KO mice of 3-4 weeks old and C57BL/6 background were recruited as the experimental group, and 26 wild type (WT) mice of the same age and background were recruited as the control group. Three-chamber test and open field test were used to observe the social interaction, anxiety, and repetitive behaviors in mice. After that, their brain weight and size were measured, and the number of hippocampal neurons were observed by Nissl staining. Furthermore, the CACNA1H heterozygote mice were interbred with Thy1-GFP-O mice to generate CACNA1H^-/--Thy1⁺(KO-GFP) and CACNA1H^+/+-Thy1⁺ (WT-GFP) mice. The density and maturity of dendritic spines of hippocampal neurons were observed. RESULTS: In the sociability test session of the three-chamber test, the KO mice spent more time in the chamber of the stranger mice than in the object one (F_{1, 14}=95.086, P < 0.05; Post-Hoc: P < 0.05), without any significant difference for the explored preference index between the two groups (t=1.044, P>0.05). However, in the social novelty recognition test session, no difference was observed between the time of the KO mice spend in the chamber of new stranger mice and the stranger one (F_{1, 14}=18.062, P < 0.05; Post-Hoc: P>0.05), and the explored preference index of the KO mice was less than that of the control group (t=2.390, P < 0.05). In the open field test, the KO mice spent less time in the center of the open field apparatus than the control group (t=2.503, P < 0.05), but the self-grooming time was significantly increased compared with the control group (t=-2.299, P < 0.05). Morphological results showed that the brain weight/body weight ratio (t=0.356, P>0.05) and brain size (t=-0.660, P>0.05) of the KO mice were not significantly different from those of the control group, but the number of neurons were significantly reduced in hippocampal dentate gyrus compared with the control group (t=2.323, P < 0.05). Moreover, the density of dendritic spine of dentate gyrus neurons in the KO-GFP mice was significantly increased compared with the control group (t=-2.374, P < 0.05), without any significant difference in spine maturity (t=-1.935, P>0.05). CONCLUSION CACNA1H KO mice represent autistic-like behavior, which may be related to the decrease in the number of neurons and the increase in the density of dendritic spine in the dentate gyrus.
Animals ; Autistic Disorder/genetics* ; Calcium Channels, T-Type/genetics* ; Gene Knockout Techniques ; Hippocampus ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons