Objective:To evaluate the role of Toll-like receptor 4 (TLR4)/nuclear transcription factor κB (NF-κB) signaling pathway in long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal rats.Methods:Seventy-five SPF healthy newborn Sprague-Dawley rats of either sex, aged 6 days, weighing 12-20 g, were divided into 3 groups ( n=25 each) using a random number table method: control group (group C), multiple exposures to sevoflurane anesthesia group (group S) and TLR4 inhibitor plus multiple exposures to sevoflurane anesthesia group (group I+ S). The rats in group S and group I inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. TLR4 inhibitor TAK-242 10 mg/kg was intraperitoneally injected before each exposure to sevoflurane in group I, and the equal volume of normal saline was given instead in the other two groups. The spontaneous activity was evaluated by open field test on day 29 after birth, and the cognitive function was assessed by Morris water maze test on days 30-34 after birth. After the behavioral test, the blood samples from the abdominal aorta were collected, and then the rats were sacrificed under deep anesthesia to isolate the hippocampal tissues for measurement of the levels of S100β and neuron-specific enolase (NSE) in serum and hippocampal interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) (by enzyme-linked immunosorbent assay), expression of TLR4, NF-κB p65 and phosphorylated NF-κB p65 (p-NF-κB p65) (by Western blot) and for microscopic examination of the pathological changes of hippocampal CA1 region after HE staining. Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the TLR4 expression was up-regulated, the ratio of p-NF-κB p65/NF-κB p65 was increased, the levels of serum S100β protein and NSE and hippocampal IL-1β, IL-6 and TNF-α were increased ( P<0.05), and the pathological changes in the hippocampal CA1 region were aggravated in group S. Compared with group S, the escape latency was significantly shortened, the number of crossing the original platform was increased, TLR4 expression was down-regulated, the ratio of p-NF-κB p65/NF-κB p65 was decreased, the levels of S100β and NSE in serum and hippocampal IL-1β, IL-6 and TNF-α were decreased ( P<0.05), and the pathological changes in hippocampal CA1 area were significantly attenuated in group P. Conclusions:The mechanism by which multiple exposures to sevoflurane anesthesia induces long-term cognitive impairment is related to activation of TLR4/NF-κB signaling pathway and increase in hippocampal inflammatory responses in neonatal rats.

Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in edaravone-induced attenuation of long-term cognitive impairment caused by long-time sedation with propofol in the neonatal rats.Methods:Eighty SPF healthy newborn Sprague-Dawley rats of both sexes, aged 7 days, weighing 15-20 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), propofol group (group P), edaravone+ propofol group (group EP) and Nrf2 inhibitor ML385+ edaravone+ propofol group (group MEP). Propofol 75 mg/kg was intraperitoneally injected once a day for 7 consecutive days in P group, EP group and MEP group, respectively, while the equal volume of medium/long chain fat emulsion injection was intraperitoneally injected in C group. Edaravone 3 mg/kg was intraperitoneally injected at 30 min before each propofol injection in EP and MEP groups, and ML385 15 mg/kg was intraperitoneally injected simultaneously in group MEP. The spontaneous activity was evaluated by the open field test on day 29 after birth, and the cognitive function was assessed by Morris water maze test on days 30-34 after birth. The rats were sacrificed after the end of water maze test, and brains were removed and hippocampal tissues were obtained for determination of reactive oxygen species (ROS) levels (by flow cytometry), superoxide dismutase (SOD) and malondialdehyde (MDA) levels (by enzyme-linked immunosorbent assay) and expression of Nrf2 and HO-1 (by Western blot) and for microscopic examination of the pathological changes in the hippocampal CA1 area (using HE staining). Results:There was no significant difference in the speed, distance and time of stay at the center of the open field among the four groups ( P>0.05). Compared with C group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the levels of MDA and ROS were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the pathological injury was observed in the hippocampal CA1 region in group P. Compared with P group, the escape latency was significantly shortened, the number of crossing the original platform quadrant was increased, the levels of MDA and ROS in the hippocampus were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 was up-regulated ( P<0.05), and the pathological injury in the hippocampal CA1 region was significantly alleviated in EP group. Compared with EP group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the levels of MDA and ROS were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the pathological injury was aggravated in the hippocampal CA1 region in MEP group. Conclusions:The mechanism by which edaravone attenuates long-term cognitive impairment caused by long-time sedation with propofol is related to activation of Nrf2/HO-1 signaling pathway and inhibition of oxidative stress in the neonatal rats.

Objective:To describe the status and influencing factors of the empowerment of caregivers after gastrointestinal tumor.Methods:From March 2019 to October 2019, using convenience sampling method, 124 pairs of gastrointestinal tumor patients and caregivers who were hospitalized in the general surgery and anorectal surgery of the department of Shandong Tai′an City Central Hospital and the Second Affiliated Hospital of Shandong First Medical University were selected as the subjects. A general information questionnaire, Main Caregivers′Empowerment Measurement were used as research tools. To investigate the empowerment ability of caregivers of patients with gastrointestinal tumors after operation.Results:The total caregiver′s empowerment score was 168.81 ± 19.49. The scores of each dimension ranged from high to low: relationship with caregivers (3.83 ± 0.43), expectation of care outcomes (3.80 ± 0.43), awareness of caregiving roles (3.70 ± 0.51), caregivers′ subjectivity (3.37 ± 0.60), caregiving beliefs (3.34 ± 0.67), caregiving knowledge and skills (3.27 ± 0.73), personal resources (2.94 ± 0.65), goodwill caregiving (2.85 ± 0.65) , the scruples around (2.75 ± 0.88). Multiple linear regression results showed that, patient gender, whether the disease is first attack, whether the patient is aware of the disease, the caregiver marriage, and the caregiver working status were the influencing factors of the caregiver′s empowerment ability after gastrointestinal tumor operation ( t values were -8.15-8.72, R2=0.62, all P<0.05). Conclusions:There is room for further improvement in the empowerment of caregivers after gastrointestinal tumor surgery, especially in personal resources, goodwill care and scruples around. The results suggest that medical staff should guide caregivers to emancipate their minds, enhance the breadth of empowerment, and promote self care and fast rehabilitation of patients.

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

Optical coherence tomography (OCT) is a new technique applied in cardiovascular system. It can detect vessel intimal, small structure of plaque surface and discover small lesions with its high axial resolution and quantification character. Especially with the application of OCT in characterization of coronary atherosclerotic plaque, diagnosis and treatment strategy making, optimizing percutaneous coronary intervention therapy and assessment after stent planting make the OCT become an efficient tool for cardiovascular disease diagnosis and treatment. This paper presents a novel coronary vessel intimal sequence extraction method based on prior boundary constraints in OCT image. On the basis of conventional Chan-Vese model, we modified the evolutionary weight function to control the evolutionary rate of boundary by adding local information of boundary curve. At the same time, we added the gradient energy term and intimal boundary constraint term based on priori boundary condition to further control the evolutionary of boundary curve. At last, coronary vessel intimal is extracted in a sequence way. The comparison with vessel intimal, manual segmented by clinical scientists (golden standard), indicates that our coronary vessel intimal extraction method is robust to intimal boundary blur, distortion, guide wire shadow and plaque disturbs. The results of this study can be applied to clinical aid diagnosis and precise diagnosis and treatment.

Objective:To investigate the feasibility of dynamic turbidity method for the detection of bacterial endotoxin content in influenza split vaccine. Methods: According to the bacterial endotoxin detection method described in general rule 1143 in Chinese Pharmacopoeia (2015 edition), the reliability test for standard curves of influenza split vaccine, the interference initial screening test, the interference verification test and the endotoxin content were performed or determined, and the results were compared with those by the gel method for the same batches of vaccine. Results:The results of reliability test for standard curves were accordance with the reg-ulations. In the interference initial screening test, vaccine was diluted by 160 times, 320 times and 640 times, and the recovery was between 50% and 200%, which showed no interference. The results of the interference verification test further proved that vaccine with 640 times dilution had no interference effect on test. The bacterial endotoxin contents of 10 batches of influenza split vaccine deter-mined by the turbidity method were less than the limit value of 20 EU·ml-1 , and the results were the same as those determined by the gel method. Conclusion:It is feasible to detect the content of bacterial endotoxin in influenza split vaccine by the dynamic turbidity method, which is worthy of promoted application.

Objective To analysis the clinical diagnosis and treatment of the scaphoid and lunate bone fracture with (or) wrist dislocation.Methods A retrospective analysis of the clinical data included 77 cases,which got admitted according to the inclusion and exclusion criteria and followed up completely from 2005 to 2013.In this group,there were 64 males and 13 females whose age arranged from 15 to 73 with a mean age of 31.9.There were 41 cases of simple fracture,32 cases of bone fracture with dislocation and 4 cases of simple dislocation.Treatment of cases was divided into the conservative treatment group (9 cases) and the surgery group (68 cases).The surgery group was further divided into four subgroups according to surgical method (i.e.compression screw fixation,Kirschner wire fixation,proximal row of carpal resection,and lunate excision head shaped bone transposition).Clinical outcome was evaluated based on modified Mayo wrist score and X-ray.Results All of 77 patients were followed up completely.Follow-up time arranged from 6 months to 8 years,with an average follow-up time of 3 years and 5 months.9 cases were treated conservatively.In the surgical treatment group,there were 36 cases of compression screw fixation,34 cases of Kirschner wire fixation,1 case of proximal row of carpal resection and 1 case of the lunate bone resection heads transposition.The average healing time of compression screw group was 6.1 weeks and the Kirschner group was 7 weeks.According to the modified Mayo wrist score,excellent:51 cases (66.2％),good:11 cases (14.3％),fair:9 cases,and poor:6 cases.The rate of excellent and good was 80.5％.The cure rate of compression screw treatment was 97％,and 85％ of Kirschner.The difference of cure rate was statistically significant.After surgery,there were four cases that got scaphoid malunion.The degree of deformity was not serious with only one case happened in the dominant hand,and the wrist pain got better after symptomatic treatment.1 case of scaphoid fracture with dislocation had the problem of wrist instability.18 weeks later,with ligament tightening surgery,postoperative Mayo score went back to excellent.Conclusion Lateral X-ray film of wrist is a preferred method for the examination of scaphoid and lunate fractures with (or) dislocation.Since it's easy to misdiagnose,films of special position are needed to be added.Surgery is preferred for treatment,and the selecting of surgical methods are based on the situation of fracture and dislocation.The advantages of screw fixation are obvious.

Background and purpose:RASSF10 acts as a kind of tumor suppressor in various tumor tissues, but researches in cardiac adenocarcinoma has not been reported. This study aimed to detect the methylation status and expression ofRas-association domain family 10 (RASSF10) in gastric cardia adenocarcinoma (GCA), and explore its role in occurrence and development of GCA.Methods:Methylation speciifc polymerase chain reaction (MSP), reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry method were respectively used to detect methylation status, mRNA expression and protein expression ofRASSF10 in 81 GCA tissues and corresponding normal tissues.Results:The promoter methylation frequency ofRASSF10 in GCA tissues (64.20%, 52/81) was signiifcantly higher than that in corresponding normal tissues (20.99%, 17/81,P<0.05), and was closely correlated with TNM stages, differential degree and lymph node metastasis (P<0.05). RASSF10 mRNA expression in GCA tissues (0.57±0.05) was significantly lower than that in corresponding normal tissues (0.78±0.02,P<0.05), and was closely correlated with TNM stages and lymph node metastasis (P<0.05). Protein expression of RASSF10 in GCA tissues (31.10%, 26/81) was signiifcantly lower than that in corresponding normal tissues (71.60%, 58/81,P<0.05), and was closely correlated with TNM stages, differential degree and lymph node metastasis (P<0.05). The promoter methylation frequency ofRASSF10 in GCA tissues was inversely related to its protein expression.Conclusion:Inactivation of RASSF10 caused by aberrantmethylation in the promoter region may be closely correlated with the GCA tumorgenesis.

ObjectiveTo explore the safety and therapeutic effect of 8 patients with esophageal Hiatal Hernia treated by laparoscopic hernia repair.MethodsA retrospective analysis was performed on the clinical data of 8 patients with esophageal Hiatal Hernia form Jun.2009 to Jun. 2010.Among the participants,3 conducted 360-degree fundoplication,5 conducted partial(270-degree) fundoplication.Silk sutures were used for the repair of esophageal perforation in 4 patients,and patch repair was used for the other 4 cases.ResultsEight patients were treated by laparoscopic hernia repair,and all of them were cured without postoperative complications.The mean duration of surgery was ( 120 ± 30) min,with average blood loss ( 50 ± 12 ) ml.Patients had a mean postoperative hospital stay of(4.5 ± 2.5 )days.All the patients were followed up for 1 to 2 years,and no case was found to be relapsed.ConclusionTotal laparoscopic hernia repair is minimally invasive,with short recovery course,less pain after surgery,little complication and short hospitalized time.Laparoscopic Hernia repair should be the preferred effective operation method for patients with esophageal Hiatal Hernia.

Objective To introduce our experiences of reconstruct the first web space using flaps.Methods One hundred and twelve patients sustained contracture of the first, summarized the indications of different flaps in coverage of the first webspace and their prognosis of these flaps were retrospectively reviewed.Results The local flaps, such as double Z-plasty or Z-plasty, were suitable to cover minor contracture of the first webspace; the dorsal flap arising from the index finger was suitable for the coverage of the medium contracture, and the posterior interosseous artery flap or the reverse antebrachial island flap based on the dorsal branch of the anterior interosseous artery suitable for the severe cases. Conclusion The usage of flaps is important to resume the cosmetic shape and function of the first webspace after release of the contracture of the first webspace.