1.Effect of β-adrenergic receptor blockers on the sleep architecture of mice
Jing QU ; Yutao LIANG ; Lei HAN ; Ye XING ; Long WANG ; Zhuochao LIN ; Kepeng LIU ; Guangsen SHI
Journal of China Pharmaceutical University 2025;56(4):498-506
Recent studies have identified a missense mutation in the β1-receptor (ADRB1-A187V) that exerts a pronounced impact on human sleep, with a noted decrease in protein abundance in vivo. The administration of β-blockers is frequently associated with sleep disturbances in clinical settings. In this study, we assessed the influence of various β-blockers on sleep within mouse models. Our findings indicated that β-blockers could induce varying degrees of arousal, sleep disruption, and a decrease in REMS (rapid eye movement sleep). We examined the dose-dependent effects of metoprolol and nebivolol on both sleep and cardiac functionality in both wild-type and Adrb1-A187V mutant mice. Our data suggested that, in contrast to cardiac effects, higher doses of metoprolol are required to have noted impact on sleep. No genotype effect was observed with metoprolol in terms of sleep or cardiac function. In contrast, the mutant mice demonstrated increased sensitivity to nebivolol, which exacerbated sleep fragmentation and impeded the onset of REMS. This study is expected to provide some reference for minimizing the occurrence of sleep disorders and reducing the adverse reactions of drugs to the greatest extent.
2.Behavioral changes of transgenic mice carrying Adrb1-A187V mutation with short sleep duration under different dietary conditions
Ziping SONG ; Lei HAN ; Zhuochao LIN ; Guangsen SHI
Journal of Southern Medical University 2024;44(10):1887-1897
Objective To observe the effects of restricted and high-fat diets on behavioral changes of wild-type(Adrb1+/+)and transgenic mice carrying Adrb1-A187V mutation(Adrb1+/m)with short sleep durations.Methods Adrb1+/+and Adrb1+/m C57BL/6 mice were randomized into normal chow group(25 Adrb1+/+and 26 Adrb1+/m mice for behavioral monitoring),odor retention fasting group(17 Adrb1+/+and 19 Adrb1+/m mice for behavioral monitoring;6 Adrb1+/+mice and 6 Adrb1+/m mice for EEG/EMG monitoring),absolute fasting group(6 Adrb1+/+and 4-5 Adrb1+/m mice for behavioral monitoring;6 Adrb1+/+and 6 Adrb1+/m mice for EEG/EMG monitoring),and high-fat diet group(6 Adrb1+/+and 7 Adrb1+/m mice for behavioral monitoring;6 Adrb1+/+and 6 Adrb1+/m mice for EEG/EMG monitoring).Electrodes for EEG and muscle activity monitoring were implanted on the skulls of the mice.After 24 h of odor retention fasting,absolute fasting,or high-fat feeding,the mice were observed for behavioral changes adapted to diet changes.Results In odor retention fasting experiment,Adrb1+/m mice exhibited more stable fluctuations of activities with mildly reduced movement and prolonged sleep duration,indicating enhanced starvation resistance.In absolute fasting experiment,Adrb1+/m mice showed significantly increased nighttime water intake,improved rhythmicity in water intake(frequent intakes in small amounts),and increased duration of non-rapid eye movement sleep(NREM).In the high-fat diet experiment,Adrb1+/m mice showed higher levels of activity with increased instances of nighttime rearing,longer movement distances,and increased rapid eye movement sleep during daytime.Conclusion Adrb1+/m mice can quickly respond to environmental changes and under restricted dietary conditions,they can conserve energy by increasing sleep to maintain energy homeostasis but show higher levels of activity under high-fat dietary conditions.
3.Behavioral changes of transgenic mice carrying Adrb1-A187V mutation with short sleep duration under different dietary conditions
Ziping SONG ; Lei HAN ; Zhuochao LIN ; Guangsen SHI
Journal of Southern Medical University 2024;44(10):1887-1897
Objective To observe the effects of restricted and high-fat diets on behavioral changes of wild-type(Adrb1+/+)and transgenic mice carrying Adrb1-A187V mutation(Adrb1+/m)with short sleep durations.Methods Adrb1+/+and Adrb1+/m C57BL/6 mice were randomized into normal chow group(25 Adrb1+/+and 26 Adrb1+/m mice for behavioral monitoring),odor retention fasting group(17 Adrb1+/+and 19 Adrb1+/m mice for behavioral monitoring;6 Adrb1+/+mice and 6 Adrb1+/m mice for EEG/EMG monitoring),absolute fasting group(6 Adrb1+/+and 4-5 Adrb1+/m mice for behavioral monitoring;6 Adrb1+/+and 6 Adrb1+/m mice for EEG/EMG monitoring),and high-fat diet group(6 Adrb1+/+and 7 Adrb1+/m mice for behavioral monitoring;6 Adrb1+/+and 6 Adrb1+/m mice for EEG/EMG monitoring).Electrodes for EEG and muscle activity monitoring were implanted on the skulls of the mice.After 24 h of odor retention fasting,absolute fasting,or high-fat feeding,the mice were observed for behavioral changes adapted to diet changes.Results In odor retention fasting experiment,Adrb1+/m mice exhibited more stable fluctuations of activities with mildly reduced movement and prolonged sleep duration,indicating enhanced starvation resistance.In absolute fasting experiment,Adrb1+/m mice showed significantly increased nighttime water intake,improved rhythmicity in water intake(frequent intakes in small amounts),and increased duration of non-rapid eye movement sleep(NREM).In the high-fat diet experiment,Adrb1+/m mice showed higher levels of activity with increased instances of nighttime rearing,longer movement distances,and increased rapid eye movement sleep during daytime.Conclusion Adrb1+/m mice can quickly respond to environmental changes and under restricted dietary conditions,they can conserve energy by increasing sleep to maintain energy homeostasis but show higher levels of activity under high-fat dietary conditions.
4.Surgical treatment of duodenal fistula with intra-abdominal infection
Pengfei MA ; Sen LI ; Yanghui CAO ; Junli ZHANG ; Chenyu LIU ; Xijie ZHANG ; Zhenyu LI ; Changzheng LI ; Guangsen HAN ; Yuzhou ZHAO
Chinese Journal of General Surgery 2023;38(2):101-104
Object:To explore surgical treatments for duodenal fistula with intra-abdominal infection.Methods:The data of 19 patients with duodenal fistula treated at the Affiliated Tumor Hospital of Zhenzhou University between Jan 2015 and Dec 2021 were analyzed retrospectively. Surgery is performed with duodenostomy or modified duodenal shunt procedures.Result:All patients were accompanied by intra-abdominal infection, including 9 duodenal stump fistulas. All patients successfully completed the operation,11cases underwent duodenostomy, 8 case underwent modified duodenal shunt procedures. operating time was 110(60-140)min, postoperative hospitalization time was 29(9-103)d. Two patients died postoperatively. Fistula heals in other patients.Conclusion:Surgical intervention for duodenal fistula should focus on controlling the source of infection, strengthening intestinal and abdominal drainage, and reducing postoperative complications.
5.Strategies and skills of reoperation for recurrent carcinoma at anastomotic stoma after total gastrectomy
Yanhui GU ; Guangsen HAN ; Kewei ZHAI ; Yong CHENG ; Shijia ZHANG ; Chao CHEN ; Xinyu WANG ; Guoyi LI
Chinese Journal of General Surgery 2022;37(1):6-9
Objective:To evaluate the strategy and skills of reoperation for recurrent carcinoma at the stoma of esophagojejunostomy after total gastrectomy.Methods:The management experience in 18 patients at the Department of General Surgery, Tumor Hospital of Zhengzhou University from Oct 2016 to Jul 2021 were analyzed retrospectively.Results:Thirteen patients underwent left thoracoabdominal combined incision to completely remove the tumor.One patient developed anastomotic leakage, two patients developed pulmonary infection, one patient developed costochondritis, all were cured and discharged after conservative treatment; Nine patients had no postoperative complications. Two patients abandoned surgery due to high position of the tumor, 3 patients due to poor cardiopulmonary function, and were given radiotherapy and chemotherapy.The postoperative follow-up period was 4.6 to 42.9 months. Four patients died of tumor recurrence, and the remaining patients survived until the end of the follow-up. The overall 1-and 3-year recurrence-free survival rates were 100% and 20%, respectively.Conclusion:Surgery on recurrent carcinoma at esophagojejunostomy stoma after total gastrectomy, although difficult and challenging,could still benefit most patients when at the hands of expertise.
6.Prognostic value of combined serum fibrinogen to albumin ratio and serum CA724 after radical resection for stage Ⅱ/Ⅲ gastric cancer
Kelei HUA ; Yingkun REN ; Guangsen HAN ; Peijun WANG ; Mingke HUO ; Zhichuang DONG
Chinese Journal of General Surgery 2021;36(10):739-745
Objective:To explore the prognostic value of combined fibrinogen/albumin ratio (FAR) and CA724 in patients with stage Ⅱ/Ⅲ gastric cancer after radical resection.Methods:A total of 932 patients were enrolled in the study, and the best cut-off values of CEA, FAR, NLR and other variables were obtained through ROC curve analysis. According to the FAR-CA724 score, patients were divided into 3 groups: FAR-CA724=0 (CA724<3.43 ng/ml and FAR<0.083), FAR-CA724=1 (CA724≥3.43 ng/ml and FAR≥0.083) and FAR-CA724=2 (CEA≥3.43 ng/ml and FAR≥0.083).Results:After FAR-CA724 grouping, the patient's age (χ 2=12.02, P=0.002), gender (χ 2=15.91, P<0.001), tumor size (χ 2=18.22, P<0.001), hypertension (χ 2=6.35, P=0.042), tumor location (χ 2=26.09, P<0.001), degree of differentiation (χ 2=12.46, P=0.002) and pTNM staging (χ 2=6.68, P=0.035) are significantly different. Survival analysis showed that there were significant differences in OS between the three groups of patients (FAR-CA724=0, 1, and 2: 88.2%, 64.3% and 37.8%, respectively, P<0.001). By multivariate analysis FAR-CA724 is an independent risk factor affecting OS in patients with stage Ⅱ/Ⅲ gastric cancer after radical surgery. Conclusions:Preoperative FAR-CA724 may be a potential blood marker for predicting the prognosis of GC patients.
7.Application of nano-carbon lymphoid tracer method in patients with rectal cancer after neoadjuvant radiotherapy and chemotherapy
Yanghui CAO ; Xijie ZHANG ; Chenyu LIU ; Pengfei MA ; Junli ZHANG ; Guangsen HAN ; Yuzhou ZHAO
Chinese Journal of General Surgery 2021;36(2):90-92
Objective:To evaluate a nano-carbon lymphatic tracing method for patients with rectal cancer after neoadjuvant radiotherapy and chemotherapy .Method:Retrospective analysis was made on 88 patients of rectal cancer undergoing neoadjuvant chemoradiation at the Department of General Surgery, He′nan Cancer Hospital from Jan 2016 to May 2020.According to whether nano-carbon lymph node was used or not, patients were divided into nanocarbon tracer group (study group) and non-nanocarbon tracer group (control group).Results:There was statistically significant in the number of havested lymph nodes between the two groups [15(11-19) vs.9(5-12), Z=5.227, P<0.001], There was no statistically significant in the number of positive lymph nodes between the two groups [0(0-0.25) vs.0(0-1), Z=1.199, P=0.231]. There were significant differences in the ratio of patients with less than 7 lymph nodes(0/34 vs.18/54, χ 2=14.248, P<0.001) and patients with less than 10 lymph nodes (4/34 vs.29/54, χ 2=15.657, P<0.001). Conclusions:The injection of nanocarbon after neoadjuvant chemoradiotherapy can increase the number of harvested postoperative lymph nodes and the ratio of patients with lymph nodes ≥7 and ≥10, which is more beneficial for prediction of the prognosis of patients.
8.Safety of two and a half layered esophagojejunal anastomosis in total gastrectomy for gastric cancer
Pengfei MA ; Yanghui CAO ; Junli ZHANG ; Chenyu LIU ; Xijie ZHANG ; Sen LI ; Guangsen HAN ; Yuzhou ZHAO
Chinese Journal of Gastrointestinal Surgery 2020;23(10):969-975
Objective:For gastric cancer patients undergoing total gastrectomy, the esophagojejunal anastomosis is the main site of postoperative anastomotic leakage. How to improve the safety of the esophagojejunal anastomosis is a hot topic. This study evaluated the safety of double and a half layered esophagojejunal anastomosis in total gastrectomy for gastric cancer.Methods:A retrospective cohort study was conducted. Clinical data of 764 gastric cancer patients, who were diagnosed as gastric adenocarcinoma by preoperative gastroscopicbiopsy and were judged to be able to complete R0 resection by imaging examination, in the Affiliated Tumor Hospital of Zhengzhou University (Henan Cancer Hospital) from May 2015 to May 2019 were retrospectively collected and analyzed. two and a half layered esophagojejunal anastomosis was used in the treatment group (295 cases), and the routine anastomosis was used in the control group (469 cases). Postoperative complicating including anastomosis-assisted complications were compared between the two groups.Results:The baseline data of two groups were not significantly different (all P>0.05). All the patients successfully completed the operation. In observation group and control group, the total operative time [(140.7±27.0) minutes vs. (139.6±22.8) minutes], intraoperative blood loss [(200.6±111.0) ml vs. (214.4±114.1) ml], anastomosis time [(20.4±4.3) minutes vs. (19.9±4.6) minutes], time to first flatus [(4.1±1.1) days vs. (4.2±1.1) days], time to fluid diet [(5.4±1.0) days vs. (5.5±0.9) days], time to postoperative nasointestinal tube removal [(9.8±3.2) days vs. (10.0±2.3) days], and postoperative hospital stay [(15.4±6.5) days vs. (15.9±5.6) days] were not significantly different (all P>0.05). Compared to the control group, the treatment group had lower rates of anastomosis-associated complications [1.7% (5/295) vs. 4.7% (22/469), χ 2=4.768, P=0.029] and anastomotic leakage [1.0% (3/295) vs.3.4% (16/469), χ 2=4.282, P=0.039]. The differences in the incidence of anastomotic stenosis and anastomotic bleeding were not statistically significant between the two groups (both P>0.05). In the treatment group and control group, rates of total postoperative complication [34.2% (101/295) vs. 32.2% (151/469), χ 2=0.838, P=0.360] and severe complication [Clavinen-Dindo grade III and above; 4.7% (14/295) vs. 7.2% (34/469), Z=-1.465, P=0.143] were not significantly different as well. Conclusion:Two and a half layered esophagojejunal anastomosis is safe and feasible in total gastrectomy for gastric cancer and can reduce anastomosis-associated complications.
9.Retrospective analysis of curative effect of total pelvic organ resection and anal preservation in 20 patients with recurrence of cervical cancer after radical radiotherapy
Gangcheng WANG ; Chongqing GAO ; Yingjun LIU ; Guangsen HAN ; Youcai WANG ; Guoqiang ZHANG ; Liangliang DING ; Bin LI ; Baochun WANG ; Shunwu CHANG
Chinese Journal of Oncology 2020;42(3):242-246
Objective:To explore the surgical method and effect of en bloc pelvic resection and anal preservation after radical radiotherapy for cervical cancer.Methods:Clinical data of 20 cervical cancer patients with central recurrence after radical radiotherapy underwent en bloc pelvic resection in the Tumor Hospital of Zhengzhou University and Hainan Provincial People′s Hospital from January 2013 to December 2017 were retrospectively analyzed. The operative time, intraoperative blood loss, length of stay, postoperative anal function and postoperative complications were evaluated.Results:The median operation time of 20 patients with anal preservation after en bloc pelvic resection was 135.2 min, the median intraoperative blood loss was 680 ml, and the median hospitalization time was 16.5 days. Among them, 18 patients had good postoperative healing, and the anal function gradually returned to normal within 6 months after surgery, defecated 1~2 times per day.One patient showed incomplete adhesion between the external colon and the anus. One patient presented with pre-sacral infection. Postoperative pathology confirmed the recurrences in 20 patients, of which 11 cases were squamous cell carcinoma, 7 cases were adenocarcinoma, 2 cases were adenosquamous cell carcinoma.Conclusions:It is safe and reliable to preserve anus after en bloc pelvic resection for cervical cancer patients with radical radiotherapy. The anus function is good enough to improve the postoperative life quality of patients significantly.
10.Types and treatment of easily-missed, misdiagnosed intestinal obstruction after radical radiotherapy of cervical cancer
Guoqiang ZHANG ; Gangcheng WANG ; Yingjun LIU ; Youcai WANG ; Dan LI ; Chongqing GAO ; Liangliang DING ; Yang LIU ; Guangsen HAN
Chinese Journal of Oncology 2020;42(11):973-975
Objective:To investigate the types and treatment methods of easily-missed, misdiagnosed intestinal obstruction after radical radiotherapy of cervical cancer.Methods:The clinical data of 21 patients with intestinal obstruction after radical radiotherapy of cervical cancer in our hospital from May 2013 to May 2019 were collected, including the radiation dose, obstruction symptoms, surgical methods and treatment outcomes. The types and treatment methods of intestinal obstruction after radical radiotherapy of cervical cancer were further investigated.Results:The intestinal obstruction occurred in 21 patients with cervical cancer after radical radiotherapy. All patients were initially diagnosed as rectal obstruction and underwent the transverse colostomy. The obstruction symptoms were successfully resolved in 15 patients while failed in other 6 patients who then underwent the re-operation. Four patients with rectal obstruction accompanied by middle or terminal ileum obstruction underwent ileostomy, the other 2 patients with terminal ileum obstruction underwent the transverse ileal anastomosis and partial intestines exclusion surgery. All of the obstruction symptoms were alleviated.Conclusions:Rectal is the major obstruction site of the cervical cancer patients with intestinal obstruction after radical radiotherapy. However, a possibility of obstruction at the middle or end of the ileum also exists. Therefore, it is very important to avoid misdiagnosis and conduct appropriate operative treatment according to the obstruction site.

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