Objective To investigate the mechanism and clinical significance of miR-18a-5p and retinoid acid receptor-related orphan receptor-α(RORA)in the proliferation and progression of colorectal cancer(CRC)cells.Methods The expressions of miR-18a-5p and RORA in CRC cells and tissues were detected via qRT-PCR,FISH,and IHC.Cell proliferation capability was detected through EdU and CFSE assay,cell apoptosis by flow cytometry assay,and cell migration and invasion abilities by cell scratch and Transwell invasion assays,respectively.The targeted regulation of miR-18a-5p on RORA was further verified via dual-luciferase reporter assay,cell function rescue test,RT-PCR,and Western blot assay.Finally,bioinformatics was used to explore the molecular mechanism of miR-18a-5p promoting malignant proliferation,invasion,and progression of CRC via regulating RORA.Results miR-18a-5p exhibited a high expression in CRC tissues and cells(P<0.05)and promoted the proliferation,migration,and invasion of CRC cells(P<0.05).In addition,RORA served as the target gene of miR-18a-5p,and its overexpression effectively reduced the promoting function of miR-18a-5p in the malignant biological phenotype of CRC cells(P<0.05).The expression of RORA in CRC tissues showed a significantly positively correlation with the infiltration of CD8+T cells and the expression of its surface marker protein CD8A.Conclusion The targeted regulation of RORA by miR-18a-5p promotes the proliferation and progression of CRC.The miR-18a-5p/RORA regulatory pathway possibly contributes to the immune microenvironment of CRC,which can be a potential therapeutic target for CRC.

Objective To explore the effect and possible mechanism of petroleum ether extract from Gastrodia elata on A amyloid β-protein deposition in Caenorhabditis elegans(C.elegans).Methods C.elegans was used as the model organism,and the experiment was divided into blank group(Control group),GEPEE 0.5 mg·mL-1 group and GEPEE 1 mg·mL-1 group.The effects of GEPEE on paralysis,life span,oxidative stress,heat stress,reactive oxygen species(ROS)level and Aβ aggregation of C.elegans were investigated,qRT-PCR was used to detect the changes of gene expression related to insulin/IGF-1 signaling pathway(IIS)in C.elegans.The main components were analyzed by high performance liquid chromatography(HPLC).Results Compared with Control group,GEPEE could significantly improve the paralysis phenotype of C.elegans(P<0.01),prolong the lifespan of C.elegans(P<0.01),enhance the motility of C.elegans(P<0.01),and increased the resistance to external oxidative stress(P<0.01),the stress ability of high temperature(P<0.01),improved the deposition of Aβ in vivo(P<0.01),decreased the ROS content in C.elegans(P<0.01),decreased the expression levels of Aβ and DAF-2(P<0.01),increased the expression levels of DAF-16 and its target genes SOD-3,GSH-Px,HSF-1 and its target gene HSP-16.2,SKN-1 and its target gene GST-4(P<0.01).Its main components were p-hydroxybenzyl alcohol and p-ethoxylbenzyl alcohol by HPLC.This study showed that GEPEE can reduce Aβ-induced toxicity in CL4176 C.elegans by reducing ROS level in vivo,increasing antioxidant level and regulating IIS pathway.Conclusion GEPEE can inhibit the toxicity of Aβ protein,and its mechanism is related to the regulation of IIS signaling pathway.

Objective:To evaluate the role of ketamine in postoperative cognitive dysfunction (POCD) and to clarify the association with subdiaphragmatic vagus nerve in mice.Methods:One hundred and forty-four SPF healthy male C57BL/6J mice, aged 18 months, weighing 32-35 g, were divided into 8 groups ( n=18 each) using a random number table method: sham operation group (group C), surgery group (group S), ketamine + surgery group (group SK), ketamine + surgery + subdiaphragmatic vagotomy group (group SK+ SDV), pseudo germ-free mice+ normal saline group (group GM+ V), pseudo germ-free mice that received fecal microbiota transplantation (FMT) from group S mice group (group GM+ S), pseudo germ-free mice that received FMT from group SK mice group (group GM+ SK), and pseudo germ-free mice received subdiaphragmatic vagotomy and FMT from group SK mice group (group GM+ SDV+ SK). Tibial fracture internal fixation was performed under anesthesia with 2.0% isoflurane. Ketamine 50 mg/kg was intraoperatively administered at the beginning of the suture in group SK. The fecal samples were collected at 24 h after surgery to prepare fecal bacteria filtrate in S and SK groups. The dorsal and ventral branches of subdiaphragmatic vagus nerve were cut prior to ketamine administration in SK+ SDV group and prior to FMT in GM+ SDV+ SK group. Broad-spectrum antibiotics dissolved in drinking water were given ad libitum to mice for 14 consecutive days at 2 weeks before FMT or subdiaphragmatic vagotomy and replaced once every 2 days to establish the pseudo germ-free model. Pseudo germ-free mice were gavaged with normal saline or fecal suspension 200 μl obtained from mice for 14 consecutive days at fixed time starting from 14 days after antibiotic intervention in GM+ SK and GM+ SDV+ SK groups. While normal saline was given instead for 14 consecutive days in GM+ V group. The fecal samples were collected after tibial fracture internal fixation or at 24 h after completion of FMT for 16S rRNA gene sequence analysis. The contents of interleukin-6 (IL-6), IL-17, tumor necrosis factor-alpha (TNF-α), IL-4 and IL-10 in the hippocampus were measured by enzyme linked-immuno-sorbent assay at 24 h after surgery or FMT. The spatial memory and learning ability was assessed by the Morris water maze test at 24 h after surgery or FMT. Results:Compared with group Sham, Simpson′s diversity index, Shannon index and Ace index were significantly decreased, the contents of IL-6, IL-17 and TNF-α were increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group S ( P<0.05). Compared with group S, Simpson′s diversity index, Shannon index and Ace index were significantly increased, the contents of IL-6, IL-17 and TNF-α were decreased, contents of IL-4 and IL-10 were increased, the escape latency in the training and testing phases and swimming distance were shortened, and the time spent in the target quadrant was prolonged in group SK ( P<0.05). Compared with group SK, Simpson′s diversity index, Shannon index and Ace index were significantly decreased, the contents of IL-6, IL-17 and TNF-α were increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group SK+ SDV ( P<0.05). Compared with group GM+ V, the contents of IL-6, IL-17 and TNF-α were significantly increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group GM+ S ( P<0.05). Compared with group GM+ S, the contents of IL-6, IL-17 and TNF-α were significantly decreased, contents of IL-4 and IL-10 were increased, the escape latency in the training and testing phases and swimming distance were shortened, and the time spent in the target quadrant was prolonged in group GM+ S ( P<0.05). Compared with group GM+ SK, the contents of IL-6, IL-17 and TNF-α were significantly increased, contents of IL-4 and IL-10 were decreased, the escape latency in the training and testing phases and swimming distance were prolonged, and the time spent in the target quadrant was shortened in group GM+ SDV+ SK ( P<0.05). Conclusions:Ketamine can improve intestinal flora disorders and reduce POCD in mice, and the mechanism may be related to subdiaphragmatic vagal nerve conduction.

Objective:To investigate the workflow, feasibility and advantages of respiratory navigator-guided stereotactic body radiation therapy (SBRT) of liver malignancies on the magnetic resonance linear accelerator (MR-linac).Methods:Clinical data of 10 patients with liver cancer treated with respiratory navigator-guided SBRT on the MR-linac from September to December 2021 were analyzed retrospectively. All patients underwent CT and MR simulated localization, and plain, enhanced and 4D CT scan, and T 1 3D MR and T 2 3D MR images were collected. The expiratory 4D CT was chosen to design the reference plan. The T 2 3D navigator MR image (end-exhalation) was collected before treatment, the target position was adjusted or the target shape was modified in combination with the real-time monitoring 2D MR image and appropriate online adaptive planning process was selected. Then, the ability of CT, T 2 3D and T 2 3D navigator MR images to display the tumor was evaluated by naked eye. The changes of target volume were calculated. Dosimetric differences between the adaptive and reference plans were compared. The efficacy and adverse reactions of patients were evaluated. Results:In the free breathing state, the T 2 3D navigator MR image was significantly better than T 2 3D MR image to clearly display the tumor and its boundary. The adaptive plans of adapt-to-position (ATP) and adapt-to-shape (ATS) adopted by 10 patients was 37 times and 22 times respectively. The tumor subsided significantly in 3 patients. The average target conformal index (CI) of the adaptive plans was no different from that of the reference plans, but the gradient index (GI) was higher ( P<0.05), especially in the ATS plans. Compared to the reference plans, the normal liver V 5 Gy, V 10 Gy and D mean were almost the same, but the average MU was increased with a significant difference in the ATP adaptive plans ( P<0.05). The average of MU, segments and normal liver D mean and V 10 Gy in the ATS adaptive plans were lower than those in the reference plans, and the liver V 5 Gy was slightly increased. Seven patients were evaluated after 1 month and 3 months. The local control of lesions was promising. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusion:Respiratory navigator on MR-linac improves the visual clarity of tumors and online MR images, and shows its advantages to guide the adaptive precision radiotherapy of liver tumors, especially in SBRT.

Objective:To investigate the safety and mid-term efficacy of robotic versus laparoscopic total mesorectal excision surgery in rectal cancer.Methods:A total of 240 patients were diagnosed with rectal cancer at the Anorectal Department of Gansu Provincial Hospital from Aug 2015 to Mar 2021, 112 patients underwent laparoscopic total mesorectal excision (L-TME group) and 128 patients did robotic-assisted total mesorectal excision (R-TME group).Results:Compared to the R-TME group, the L-TME group had higher conversion rate (5.4% vs. 0.8%, χ2=4.417, P=0.036), higher incidence of complications (32.1% vs. 17.2%, χ2=7.290, P=0.007), higher circumferential resection margin involvement (7.1% vs. 1.6%, χ2=4.658, P=0.031), lower 3-year DFS and OS(74.1% vs. 85.2%, χ2=4.962, P=0.026) and (81.3% vs. 91.4%, χ2=5.494, P=0.019), lower 3-year DFS and OS in AJCC stage Ⅲ(52.5% vs. 76.1%, χ2=5.799, P=0.016) and (65.0% vs. 84.8%, χ2=4.787, P=0.029). Conclusion:R-TME can achieve better oncological outcomes and is more beneficial for RC patients compared with L-TME, especially for those with stage Ⅲ rectal cancers.

Objective:To report our experience in treatment of patients with orthopaedic trauma during COVID-19 epidemic.Methods:We retrospectively analyzed the 67 patients with orthopedic trauma who had been treated at Department of Orthopaedics, Peking Union Medical College Hospital from February 1 to March 31, 2020. After screening for COVID-19 infection was performed under strict protection, the patients were diagnosed and assigned to outpatient emergency treatment or hospitalization according to their specific condition. Twenty-six patients were treated at the outpatient emergency department. They were 8 males and 18 females with an average age of 69.5 years. Of them, 6 with vertebral compression fracture were placed on bed brakes, 14 with limb fracture immobilized after close reduction, 2 with skin laceration treated with debridement and suture, and 4 with hip fracture immobilized in bed. In the 41 hospitalized patients, there were 14 males and 27 females with an average age of 68.5 years. In them, hemiarthroplasty was performed for 7 femoral neck fractures, kyphoplasty for 5 vertebral compression fractures, total elbow arthroplasty for one humeral intercondylar fracture, exploration and suture for one case of Achilles tendon rupture, and internal fixation surgery for the remaining 27 cases.Results:Most of the patients had osteoporotic fractures which accounted for 61.5% (16/26) of the outpatients and 68.3% (28/41) of the inpatients, respectively. The duration from injury to surgery averaged 2.3 days and the length of hospitalization 4.5 days for the 41 hospitalized patients, decreased compared with the corresponding data (3.1 days and 11.5 days) for the similar inpatients in the same period last year. In the 41 inpatients, fever was observed upon hospitalization in 4 cases and after operation in 26 cases, and related to their primary injury or surgical trauma in all. Acute pulmonary embolism happened during operation in one patient with femoral shaft fracture.Conclusions:The prevention and control of COVID-19 should be continued. The awareness and behavior of health care providers are expected to be enhanced by strict screening protocol, protection and supervision. The proportion of elderly patients with osteoporotic fracture increased during the COVID-19 pandemic. Shortage of blood was the major problem affecting the treatment. Timely surgical treatment should be indicated for the patients with orthopedic trauma, especially those with lower extremity fracture.

Objective:To evaluate the efficacy of acupuncture-drug balanced anesthesia in improving the outcomes following radical correction of tetralogy of Fallot (TOF) under cardiopulmonary bypass (CPB) in the pediatric patients.Methods:A total of 100 pediatric patients, aged 3-8 yr, weighing 9-24 kg, with American Society of Anesthesiologists physical status Ⅱ or Ⅲ, scheduled for elective radical correction of TOF with CPB, were divided into 2 groups ( n=50 each) using a random number table method: acupuncture-drug balanced anesthesia group (group ADBA) and conventional anesthesia group (group CA). In group ADBA, transcutaneous acupoint electrical stimulation (disperse-dense wave, frequency 2/100 Hz, current intensity 6 mA, pulse width 0.2-0.6 ms) of Baihui (GV20) and bilateral acupoints of Neiguan (PC6), Hegu (LI4), and Ximen (PC4) acupoints was performed after induction of general anesthesia and maintained until the end of surgery.In group CA, the children received combined intravenous-inhalational anesthesia, and electrodes were only applied on the same acupoints without electrical stimulation.Venous blood samples were collected for blood routine examination and for determination of the concentrations of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-alpha(TNF-α) at 30 min before surgery (T 1), 30 min after the start of surgery (T 2) and 1 h and 1, 2, 3 and 5 days after surgery (T 3-7). The length of hospital stay and development of postoperative major adverse events were recorded. Results:Compared with group CA, the plasma concentrations of IL-6, IL-8 and TNF-α at T 2-7 and white blood cell count, neutrophil count and neutrophil percentage at T 4-7 were significantly decreased, postoperative length of hospital stay was shortened ( P<0.05), and the incidence of acute lung injury was decreased obviously in group ADBA ( P<0.05). Conclusion:Acupuncture-drug balanced anesthesia can improve the outcomes following radical correction of TOF under CPB to a certain extent, and the mechanism is related to inhibiting inflammatory responses in pediatric patients.

Objective To compare effectiveness and short-term outcomes between robotic-assisted and laparoscopic surgery for radical resection of rectal cancer.Methods A total of 410 patients diagnosed with rectal cancer,undergoing robotic-assisted surgery (RAS) for rectal cancer (215 cases) and conventional laparoscopic surgery(CLS) for rectal cancer (195) from Jan 2016 to Dec 2018 were included into the present study.Operative characteristics,postoperative complications and pathologic parameters were evaluated between RAS and CLS group.Results The RAS group had less intraoperative blood loss[(107 ± 46) ml vs.(147 ±35)ml,t =3.695,P＜0.05],longer operation time[(209 ±55)min vs.(195 ± 55)min,t=2.508,P＜0.05],earlier first flatus[(3.4 ± 1.4)d vs.(5.3 ± 1.6)d,t =-14.952,P＜ 0.05],and first liquid diet time [(4.3 ± 1.5) d vs.(6.2 ± 2.6) d,t =-9.109,P ＜ 0.05],more number of dissected lymph nodes[(12.6 ± 4.3) vs.(10.6 ± 4.5),t =4.468,P ＜ 0.05] compared with those in the CLS group.But more expensive total hospitalization costs[(71 775 ±45 089) yuan vs.(66 789 ± 16 721) yuan,t =4.224,P ＜ 0.05].Conclusion Compared with laparoscopic surgery,robotic-assisted surgery has less blood loss,shorter time of first flatus,more lymph nodes yield.

Objective:To investigate the role of thoracic echocardiography in diagnosis and differential diagnosis of the right ventricular outflow tract into the right aorta with right ventricular aneurysm rupture.Methods:A total of 19 patients with sinus rupture caused by ventricular septal defect in the right ventricular outflow road were reviewed.These patients were diagnosed as aortic right coronary sinus by preoperative transthoracic echocardiography from February 2010 to September 2016 in Xiangya Second Hospital and Xiangya Medical College Affiliated Haikou Hospital.The clinical symptoms,echocardiography and intraoperative lesions were compared and analyzed among the patients.Results:The intraoperative lesions were consistent with the preoperative echocardiographic diagnosis in 16 patients.Among them,11 cases could be heard the continuous sound of the machine with systolic murmur and no tremor in left sternal rib 2-3 auscultation.The color Doppler imaging of right ventricular systolic indicated the based continuous Doppler spectrum.The preoperative echocardiography and intraoperative lesions testified the ventricular septal defect size and the right ventricular outflow tract into the right aorta with right ventricular aneurysm rupture.Among them,3 cases were complicated with other heart diseases.Other 3 cases were not accorded with the preoperative diagnosis.There were auscultation smell and noise but no tremor.The preoperative echocardiography and lesions indicated the right ruptured aneurysm of the sinus of big and long mouth,1 case with aortic valve stenosis and regurgitation,congenital aortic valve two valve malformation,1 case with aortic valve-severe reflux,1 case with pulmonary infection,and 3 cases with no intraoperative lesions in the ventricular septal defect.Conclusion:Preoperative transthoracic echocardiography is the preferred preoperative,quick and noninvasive method for ruptured aneurysm.Each stage of observation procedure and method can observe the ruptured aneurysm of aortic sinus,the location,size and adjacent ofventricular septal defect.Meanwhile,the flow spectrum characteristics of the ventricular septal defect in the right outflow tract of the right sinus aneurysm can be found by Doppler ultrasound imaging.

Objective To evaluate preoperative multislice CT angiography (MSCTA) in guidance for laparoscopic right colon cancer the complete mesocolon resection (CME).Methods From September 2014 to May 2016 data of 24 patients undergoing laparoscopic CME right colon cancer surgery,were reviewed for the guidance of MSCTA over operative surgery.Results Preoperative MSCTA clearly showed superior mesenteric vascular anatomical variation and its branch,which was in closely consistent with that seen during the operation.The superior mesenteric arteries and veins (SMA/SMV) and the ileum colon arteries and veins (ICA/ICV) were seen in all the 24 cases.There are four main types anatomic variation of gastrocolic trunk (Henle trunk),of which most often consisting of three branchs (type B),accounting for about 46％.The time of completely dissecting anatomical Henle trunk was significantly longer than that for the ileum colon vessels and the middle vessels dissection (P ＜ 0.05).Conclusion Preoperative MSCTA can clearly present anatomic variation of SMV/SMA and its branch,precisely navigate the laparoscopic right colon cancer CME surgery,reducing the incidence of intraoperative vascular complications and improving the quality of surgery.