Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.

Objective To observe the toxicity of low concentration Mn²⁺ compound combined with autophagy inhibitor chloroquine on nerve cell line PC12 cells for long-term and its mechanism. Methods PC12 cells at logarithmic growth stage were treated with 0 (control), 5, 10, 25, 50, 100, and 200 μM manganous chloride, and 5, 10, 25, 50, and 100 μM chloroquine for 24 h, respectively. The effect of manganous chloride and chloroquine on cell viability was detected by MTT assay. The combined effect of the two compounds on cell viability was determined at 24, 48 and 72 h, respectively. The mitochondrial respiratory function was further examined to explore the possible toxicity mechanism of manganous chloride and chloroquine. Results Compared with the control group, manganous chloride and chloroquine alone had inhibitory effect on cells survival in a concentration-dependent manner. Manganous chloride and chloroquine at concentrations of 40 μM and 2.5 μM, respectively, had no significant effect on cell survival. Compared with the control group, administration of 2.5 μM chloroquine alone for 24, 48 and 72 h did not significantly change cell survival and mitochondrial respiratory function. Treatment of cells with manganous chloride alone at the concentration of 40 μM for 72 h did affect mitochondrial respiratory function. However, the cell survival and mitochondrial respiratory function in the combined administration of manganous chloride and chloroquine for 72 h were significant decreased (P< 0.05). Conclusion The long-term combination of low-concentration manganous chloride and chloroquine produced an additive cytotoxicity on PC12 cells, and the toxicity mechanism may be related to the damage of mitochondrial function.

Objective:To explore the utility of applying low frequency transcranial magnetic stimulation (rTMS) in the acute stage of ischemic stroke in terms of improving upper limb motor function.Methods:Eighty ischemic stroke survivors in the acute stage were randomly divided into a control group and an experimental group, with 40 in each. In addition to routine rehabilitation, the experimental group was given low frequency rTMS, while the control group was provided with sham rTMS. Before and after 4-weeks of treatment, upper limb motor function was evaluated using the Fugl-Meyer rating scale (FMA), Wolf motor function tests (WMFTs), the modified Barthel index (MBI) and in terms of motor evoked potential (MEP) latency and amplitude.Results:There were no significant differences between the two groups before the treatment. Afterward, however, the average FMA, WMFT, MBI scores had improved significantly more in the experimental group, on average, as had the average MEP amplitude.Conclusion:Low frequency rTMS in the acute phase of ischemic stroke can improve upper limb motor function and ability in the activities of daily living.

Improving the reproducibility of biomedical research results is a major challenge. Transparent and accurate reporting of the research process enables readers to evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist that is applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as enhance the reliability, repeatability, and clinical translation of animal experimental results. The use of the ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and completeness of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is based on the best practices following the ARRIVE 2.0 guidelines in international journals, and it interprets, explains, and elaborates in Chinese the fifth part of the comprehensive version of the ARRIVE 2.0 guidelines published in PLoS Biology in 2020 (the original text can be found at https://arriveguidelines.org). This section includes the items 6-11 of Recommended 11 section, covering "Animal Care and Monitoring", "Interpretation/Scientific Implications", "Generalisability/Translation", "Protocol Registration", "Data Access" and "Declaration of Interests". Its aim is to promote a comprehensive understanding and use of the ARRIVE 2.0 guidelines among domestic researchers, to enhance the standardization of experimental animal research and reporting, and to promote high-quality development of experimental animal sciences and comparative medicine research in China.

Objective To establish a three-dimensional visualization model of complex anal fistula based on high-resolution mag-netic resonance imaging(HR-MRI),and to explore its feasibility and clinical application value.Methods The clinical and imaging data of 26 patients with complex anal fistula were analyzed retrospectively,and a three-dimensional visualization model based on HR-MRI images was established.The Parks typing,internal orifice,external orifice,branch fistula and abscess were evaluated by radiolo-gists and anorectal surgeons in HR-MRI images and the three-dimensional visualization model,and the SPSS 22.0 software was used to analyze the assessment results against the clinical surgery one by one.Results A total of 26 patients had 17 trans sphincteric fis-tulas,7 inter sphincteric fistulas,and 2 suprasphincteric fistulas,and the accuracy of Parks typing based on HR-MRI images and three-dimensional visualization model was 100％;26 patients had a total of 33 internal orifices,and the evaluation of internal orifices based on HR-MRI images was better than that of three-dimensional visualization model(P=0.180 vs P=0.022);15 patients had a total of 32 external orifices,and the evaluation of external orifices based on three-dimensional visualization model was better than that of HR-MRI images(P=0.791 vs P=0.049);20 patients had perianal abscesses,and the evaluations based on HR-MRI images and three-dimensional visualization model were both highly accurate(P=0.549 vs P=0.625);18 patients with branch fistula,the evaluation of branch fistula based on three-dimensional visualization model was significantly better than that of HR-MRI images(P=1.000 vs P＜0.001).Conclusion Based on three-dimensional visualization model of HR-MRI,the evaluation of complex anal fistula Parks typing,external orifice,branch fistula and abscess is more accurate,which is worthy of further research and promotion.

Improving the reproducibility of biomedical research results is a major challenge.Researchers reporting their research process transparently and accurately can help readers evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as the reliability, repeatability, and clinical translatability of animal experimental results. The use of ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and integrity of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is a Chinese translation based on the best practices of international journals following the ARRIVE 2.0 guidelines in international journals, specifically for the complete interpretation of the ARRIVE 2.0 guidelines published in the PLoS Biology journal in 2020 (original text can be found at https://arriveguidelines.org). The third part of the article includes the items 8-10 of ARRIVE 2.0 Essential 10, which covers "experimental animals" "experimental procedures" and "results". Its aim is to promote the full understanding and use of the ARRIVE 2.0 guidelines by domestic researchers, enhance the standardization of experimental animal research and reporting, and promote the high-quality development of experimental animal technology and comparative medicine research in China.

Objective:To investigate the predictive value of thrombus enhancement (TE) and thrombus permeability in cardioembolic thrombus with acute middle cerebral artery occlusion based on CT.Methods:The clinical and image data of 93 patients with acute middle cerebral artery occlusion who were admitted to the First Affiliated Hospital of Soochow University within 12 hours after onset from January 2020 to July 2022 were retrospectively analyzed. According to the TOAST criteria, the patients were divided into the cardioembolism (CE) group (43 cases) and the large artery atherosclerosis (LAA) group (50 cases). All patients received noncontrast CT and CT angiography, and then thrombus permeability [thrombus attenuation increase (TAI), void fraction (ε)] and TE were assessed. Independent sample t-test, Mann-Whitney U test and χ2 test were used in univariable analysis between two groups. Multivariable logistic regression analysis was used to explore the independent influencing factors for cardioembolic stroke and establish a logistic model. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the predictive value of TAI, ε, TE and the logistic model in cardioembolic thrombus with acute middle cerebral artery occlusion. Results:There were statistically significant differences in sex, atrial fibrillation, hypertension, diabetes mellitus, smoking, baseline National Institutes of health stroke scale (NIHSS), TAI, ε and TE between the CE group and the LAA group ( P<0.05). Binary logistics regression analysis showed that TAI (OR=1.300, 95%CI 1.147-1.473, P<0.001), hypertension (OR=0.116, 95%CI 0.025-0.535, P=0.006) and baseline NIHSS (OR=1.165, 95%CI 1.040-1.304, P=0.008) were independent influencing factors for cardioembolic thrombus. The ROC curve indicated that the logistic model predicted cardioembolic thrombus with the highest AUC of 0.907 (95%CI 0.848-0.966). TE predicted cardioembolic thrombus with the highest sensitivity of 90.7%. Conclusion:TE and thrombus permeability have application value for predicting cardioembolic thrombus with acute middle cerebral artery occlusion based on CT.

Osteonecrosis of the femoral head (ONFH) is one of the common and difficult-to-treat orthopedic diseases caused by a variety of factors that lead to abnormal blood flow to the femoral head, which in turn leads to deformation and collapse of the femoral head and eventually results in severe hip joint dysfunction. The key to the treatment is early diagnosis and correct treatment according to the stage classification and active prevention of further aggravation of ONFH aiming to delay or avoid hip replacement surgery in young and middle-aged patients. At present, there are various non-surgical and surgical hip-preserving modalities for early ONFH, designed to slow down the progression of the disease, prevent the femoral head from collapsing and stop the mild collapse. In recent years, with the emergence and development of bone reconstruction biomaterials, artificial bone reconstruction after scraping of ONFH lesions has shown great potential in the treatment of early ONFH. The authors review the research progress in hip-preserving modalities for early ONFH in young and middle-aged patients from non-surgical and surgical perspectives, hoping to provide a reference for clinical treatment of early ONFH.

Objective:There is no standard method for esophageal remnant gastric reconstruction for proximal gastrectomy. Reflux esophagitis caused by esophagogastrostomy remains a difficult surgical problem. To report the preliminary surgical results of novel esophagus-conical remnant gastric side overlap anastomosis (CGEO) , with particular emphasis on postoperative esophageal reflux.Methods:In June 2022, we developed a novel CGEO for laparoscopic proximal gastrectomy on two patients with Siewert type II esophagogastric junction adenocarcinoma. Surgical procedures for CGEO: (1) Laparoscopic proximal gastrectomy and preparation of conically shaped gastric remnant; (2) Determining anastomotic site of residual stomach and esophagus; (3) Side-to-side anastomosis of right esophageal wall to anterior of conical gastric remnant; (4) Valvuloplasty of esophageal stump.Results:Case 1 was a 71-year-old man with an operation time of 305 minutes and was successfully discharged from the hospital on the 9th day after surgery, and the postoperative pathology was T3N0M0. Case 2 was an 82-year-old man with an operation time of 325 minutes. He was discharged on the 10th day after surgery. In both cases, only mild esophageal mucosal changes were seen in gastroscopy, there were no obvious symptoms of esophageal reflux. There was also no significant weight change at half a year after operation.Conclusion:CGEO is moderately safe in radical surgery for proximal gastric cancer, and may have a preventive effect on the occurrence of postoperative esophageal reflux, but long-term results need to be confirmed by further studies with follow-up.

Objective:There is no standard method for esophageal remnant gastric reconstruction for proximal gastrectomy. Reflux esophagitis caused by esophagogastrostomy remains a difficult surgical problem. To report the preliminary surgical results of novel esophagus-conical remnant gastric side overlap anastomosis (CGEO) , with particular emphasis on postoperative esophageal reflux.Methods:In June 2022, we developed a novel CGEO for laparoscopic proximal gastrectomy on two patients with Siewert type II esophagogastric junction adenocarcinoma. Surgical procedures for CGEO: (1) Laparoscopic proximal gastrectomy and preparation of conically shaped gastric remnant; (2) Determining anastomotic site of residual stomach and esophagus; (3) Side-to-side anastomosis of right esophageal wall to anterior of conical gastric remnant; (4) Valvuloplasty of esophageal stump.Results:Case 1 was a 71-year-old man with an operation time of 305 minutes and was successfully discharged from the hospital on the 9th day after surgery, and the postoperative pathology was T3N0M0. Case 2 was an 82-year-old man with an operation time of 325 minutes. He was discharged on the 10th day after surgery. In both cases, only mild esophageal mucosal changes were seen in gastroscopy, there were no obvious symptoms of esophageal reflux. There was also no significant weight change at half a year after operation.Conclusion:CGEO is moderately safe in radical surgery for proximal gastric cancer, and may have a preventive effect on the occurrence of postoperative esophageal reflux, but long-term results need to be confirmed by further studies with follow-up.