Objective The novel μ opiate receptor (MOR) antagonists with biological activity was searched based on computer aided drug design method. Methods The MOR was employed as the target protein, and the Glide module of Schrodinger software was used to virtually screen the numerous compounds included in ZTNC-15 open source compound database. According to the molecular docking score, skeleton structure, binding mode and compound acquisition, one compound that may be as an antagonist was selected. The anti-fentanyl-induced acute death model of mice and the experiment of improving fentanyl-induced respiratory depression of rats were used to evaluate the biological activity of A₆ against MOR. Finally, molecular dynamics simulation method was employed to analyze the possible mechanism of MOR-A₆ interaction. Results The molecular docking score of compound A₆ was comparable to that of naloxone. The results of animal experiments showed that the LD₅₀ value of fentanyl-induced death of mice in A6 prevention administration group [13.2(95%CI 12.0-14.5) mg/kg] was 1.3 times and higher than that in model group [10.5(95%CI 9.6-11.5) mg/kg], and the mortality of mice in experimental group was significantly lower than that in model group (P<0.05); Compared with model group, the carotid oxygen saturation (SaO₂) of rats in A₆ prevention administration group increased significantly at 15, 20 and 25 min after fentanyl injection (47.91%±3.17% vs. 62.63%±4.14%, 52.99%±3.92%vs. 69.57%±3.17%, and 58.16%±2.45% vs. 77.10%±4.93%, P<0.05). Molecular dynamics simulation of A₆ and MOR showed that ASP147 amino acid residue of A₆ is consistent with the predicted results of molecular docking, and has a large contribution on binding free energy. Conclusions A novel compound A₆ has obtained by virtual screening which could effectively antagonise fentanyl-induced acute toxic death in mice and improve fentanyl-induced respiratory depression in rats. The mechanism may be related to the hydrogen bond formation of ASP147 amino acid residue with MOR.

Dystonia is a type of movement disorder disease characterized by abnormal movements and postures, which seriously affects patients' social life and quality of life. However, there are certain difficulties in positioning judgment of early intervention, efficacy analysis and prognostic evaluation at present. Resting state functional magnetic resonance imaging (rs-fMRI)is an advanced technique for measuring the brain's spontaneous nerve activity at rest. It is widely used in the study of dystonia due to its advantages of non-invasiveness, simplicity and ease of use, and diverse analysis methods. Studies have shown that dystonia is not simply a basal ganglia dysfunction, but a neural network disorder. This article briefly describes the principle and clinical application of rs-fMRI, focusing on the research progress of rs-fMRI in various dystonia diseases, which will help to further understand the pathogenesis of focal dystonia to provide functional imaging basis for the development of more effective therapeutic drugs.

It is a common phenomenon that the working ability of the people from moderate temperature areas generally decreases after entering high temperature areas, while heat acclimatization can improve the heat tolerance of human. This review summarized the molecular mechanism of the formation of heat acclimatization and the specific key markers produced after heat acclimatization from the perspectives of physiological function, biochemical metabolism and epigenetics. In addition, Genome-Wide Association Study (GWAS) strategy in exploring the main genetic differences among people with different heat adaptation was also discussed. Heat acclimatization changes the sensitivity of central and peripheral thermal effectors, reduces heart rate and increases stroke volume by regulating myocardial autonomic nerve tension to reduce endogenous heat production and accelerate exogenous heat dissipation. Heat acclimatization enhances the secretion of H₂O and sodium retention hormones such as aldosterone and arginine vasopressin and the enrichment of NaCl in diet, which expands the plasma volume to maintain cardiovascular stability. The transcriptional activity of heat shock protein (HSP) and the calcium release of mitochondrial respiratory chain increases after heat acclimatization, in which HSP70 is a potential key genetic marker to distinguish between those with good heat adaptation (hot zone soldiers, firefighters, athletes, etc.) and those with poor heat adaptation. Moderately high concentration of Na⁺, Cl^–, Ca²⁺ and low concentration of K⁺ in plasma can help to enhance heat tolerance and promote the formation of heat acclimatization, which can be used as potential markers for the study of heat acclimatization. Furthermore, heat acclimatization effect in the population has great heterogeneity. How heat acclimatization enhances human's heat tolerance and the balance between the plasticity of this heat tolerance and congenital genetic and acquired epigenetic modification need to be further explored.

Objective To investigate the effects of different arterial partial pressure of carbon dioxide (PaCO₂) on regional cerebral oxygen saturation (rScO₂) in robot assisted laparoscopic pyeloplasty (RALP) in children. Methods Forty-five children who received RALP in Pediatric Urology Department of the Seventh Medical Center of Chinese PLA General Hospital from February 2019 to February 2020 were selected as the study subjects, by adjusting tidal volume and respiratory rate maintained PaCO₂ at 35-45 mmHg (group N), 30-34 mmHg (group M) and 25-29 mmHg (group L) with 15 patients in each group. Before anesthesia (T₀), 10 min after endotracheal intubation (T₁), before lateral decubitus surgery (T₂), 30 min after pneumoperitoneum(T₃), 10 min after pneumoperitoneum (T₄), and 10 min after recumbent position (T₅), rScO₂ of affected side, percutaneous pulse oxygen saturation (SpO₂), heart rate (HR), mean arterial pressure (MAP), pharyngeal temperature (T), pH and hemoglobin (Hb)were recorded respectively. Arterial blood was extracted for blood gas analysis, and PaCO₂ was recorded, operation time was recorded after operation. Results Compared with T₀, rScO₂ in the three groups was increased significantly at T₁, and decreased significantly at T₃ in group L (P<0.05); compared with T₂, rScO₂ in group L at T₃ was significantly lower (P<0.05); compared with T₃, rScO₂ in group L was increased significantly at T₄ and T₅ (P<0.05). Compared with group N, rScO₂ in group L was decreased significantly at T₃ (P<0.05). Two-factor ANOVA showed that there was no interaction between group and pneumoperitoneum at T₂ and T₃, T₃ and T₄ in the three groups (P>0.05); compared with T₂, rScO₂ at T₃ in group L was significantly lower (P<0.05); compared with T₃,rScO₂ at T₄ in group L was significantly increased (P<0.05). There were no significant differences in SpO₂, HR, MAP, T, pH and Hb among the threes groups at each time point of T₀-T₅. Conclusion Pneumoperitoneum resulted in a significant decrease in rScO₂ on the affected side when PaCO₂ was within 25-29 mmHg during pediatric RALP and the risk of the cerebral oxygen supply-demand unbalance increased.

Objective To analyze the clinical features, diagnosis and treatment and prognosis of acute megakaryocytic leukemia (AMKL), and then review the relative of AMKL. Methods Retrospectively study the clinical data of 14 AMKL patients admitted to Fujian Medical University Union Hospital and the First Affiliated Hospital of Gannan Medical University from January 2016 to May 2021, analyze and discuss the clinical features, diagnosis and differential diagnosis, treatment and prognosis of AMKL patients, and search domestic or foreign literature for the literature review at the same time. Results A total of 14 AMKL patients were included in present study, including 6 children [4 males and 2 females, with a median age of 2 years (13 months to 6 years)]; 8 adult patients [5 males and 3 females, with a median age of 57 (19-78) years]. The clinical manifestations of the patients were mainly non-specific symptoms of blood diseases. All patients underwent bone marrow biopsy, and a large number of primitive megakaryocytes were seen under the microscope. Except for 2 patients with incomplete flow immunophenotyping, cytogenetics and molecular biology tests, all the remaining 12 patients had megakaryocyte antigens (CD41, CD61, CD42b) expression, accompanied by genetic or molecular biology abnormalities. Except for 1 patient who survived after bone marrow transplantation and 1 patient who was lost to follow-up, the remaining 12 patients died, the median survival time was 5.5 (0–21) months. A total of 249 cases of AMKL patients in mainland of China (excluding Hong Kong, Macao and Taiwan) were reported from 2002 to 2022,of which 16 cases were transformed by other hematological tumor diseases: 6 cases were transformed by chronic myeloid leukemia(CML), 4 cases were transformed by myelodysplastic syndrome (MDS), 3 cases were transformed by myelofibrosis (MF), 2 cases were transformed by primary immune thrombocytopenia (ITP), and 1 was transformed by acute lymphoblastic leukemia (ALL).Among the 249 AMKL patients, 24 survived and 225 died. Most of the causes of death were disease progression, recurrence after chemotherapy or transplantation, severe infection, and fatal hemorrhage. Conclusions AMKL is rare and has an extremely poor prognosis with lack of specificity in clinical manifestations. It is helpful for diagnosis and differential diagnosis of AMKL by the results of bone marrow routine and pathology, flow cytometry, cytogenetics, molecular biology and electron microscopy. Clinical trials should be the first choice for the treatment of AMKL, correspondingly, close monitoring of measurable residual disease (MRD),and the remission induction chemotherapy combined with epigenetic drugs and targeted therapy may benefit patients. In addition,AMKL patients should undergo hematopoietic stem cell transplant as soon as possible after the first complete remission induced by standard chemotherapy, which will maximize the prognosis of patients.

Objective Use aspirin to induce mouse inflammatory bowel disease model, and investigate whether Lactobacillus acidophilus LA-GHB1756 can alleviate this type of enteritis injury. Methods A total of 40 male BALB/c mice (6-8 weeks old) was randomized into four groups: control group, aspirin group, LA low-dose group, and LA high-dose group. Except for the control group, the remaining groups were given 0.5 mg/(100 g·d) aspirin solution by gavage for eight weeks to induce inflammatory bowel disease. The LA low-dose and high-dose groups received an additional 2000 cfu/(100 g·d) and 10 000 cfu/(100 g·d) of LA-GHB1756 bacterial liquid, respectively. Accordingly, the control and aspirin groups received the same volume of normal saline through gavage. We then monitored the mouse's body weight, defecation status, hair color, and other conventional indicators, colon macroscopic and pathological staining. We used ELISA to detect intestinal tissue MPO content, serum tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) expression. We employed Western blotting to detect intestinal tissue NF-κB p65 expression levels. Results The general observation of mice in each group showed that LA-GHB1756 could improve the diarrhea, hair, and mental status of aspirin-induced mice. In the 8th week, the body weight of mice in the aspirin group was (21.6±0.5) g. The body weight was statistically significantly improved in the LA low-dose and high-dose groups, which were (22.8±0.4) g and (23.1±0.3) g, respectively (P<0.05). The colon morphology and pathological results showed that LA-GHB1756 could alleviate intestinal mucosal edema and inflammation caused by aspirin in mice. The colon length of mice in the aspirin group was(5.80±0.43) cm, and the colon length of low-dose and high-dose LA groups was (6.17±0.15) cm and (6.50±0.26) cm, respectively. This length improvement was statistically significant (P<0.05). The results of MPO content in intestinal tissues showed that aspirin group was (95.90±11.34) pg/mg, the MPO content in LA low-dose group and LA high-dose group were (76.03±8.72) pg/mg and (51.40±9.12) pg/mg respectively, which was significantly decreased compared with aspirin group, the difference was statistically significant (P<0.05). The results of serum TNF-α and IL-6 expression showed that the concentrations of TNF-α and IL-6 in aspirin group were (238.75±17.80) pg/mg and (292.00±15.51) pg/mg, respectively, while those in LA low-dose group were (207.75±12.04) pg/mg and (250.25±11.50) pg/mg, respectively, LA high-dose group were (80.25±10.24) pg/mg and (108.50±13.38) pg/mg, respectively. Compared with aspirin group, TNF-α and IL-6 contents in LA low-dose group and LA high-dose group were statistically significantly decreased (P<0.05). The expression of NF-κB p65 was increased up to 5.07 fold in aspirin group when compared with control group. This level was statistically significantly decreased to 83.74% and 82.95% in LA low-dose and high-dose groups, respectively (P<0.05). Conclusion LA-GHB1756 can relieve intestinal inflammation in mice caused by aspirin, this effect may be related to the inhibition of MPO and NF-κB p65 expression in intestinal tissue.

Objective To evaluate the protective effect of Rhubarb on vascular endothelial cell function in the sepsis patients. Methods We carried out a prospective, single-center, randomized controlled study based on 41 patients with sepsis who admitted to the Intensive Care Unit of the 908th Hospital of PLA. The patients were randomly divided into Rhubarb treatment group (n=20) and control group (n=21). Blood samples were collected before, 24 h and 72 h after the medication. Conventional coagulation tests [prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, thrombin time (TT), fibrin degradation products (FDP), D-dimer, antithrombin (AT-Ⅲ), platelet count, platelet distribution width] and coagulation molecular markers including thrombomodulin (TM), tissue plasminogen activator-inhibitor complex (t-PAIC), thrombin- antithrombin complex(TAT), plasmin-α₂ antiplasmin complex (PIC) were detected and statistically analyzed. Results The fibrinogen level [(3.5±1.0) g/L] at the 72 h after administration in Rhubarb treatment group was significantly higher than that in control group [(2.7±0.8) g/L] and Rhubarb treatment group before administration [(2.7±0.9) g/L] (P<0.05). Compared with the serum TM [19.0(15.5,22.6) TU/ml] and t-PAIC [15.4(9.7, 20.9) ng/ml] levels before treatment in control group, the TM [27.3(20.8, 31.2) TU/ml] and t-PAIC [22.2 (15.5, 38.6) ng/ml] at the 72 h after administration in control group significantly increased (P<0.05). Compared with TM [27.3(20.8, 31.2) TU/ml] and t-PAIC [22.2(15.5, 38.6) ng/ml] of control group, the TM [13.2(10.9, 18.0) TU/ml] and t-PAIC [9.2(7.3, 23.1) ng/ml] at the 72 h after administration in Rhubarb treatment group were significantly decreased (P<0.05).Compared with the serum TM [19.7(17.1, 23.4) TU/ml] levels before treatment and the TM [18.6(15.3, 21.1) TU/ml] at the 24 h after administration in Rhubarb treatment group, the TM at the 72 h after administration were significantly decreased (P<0.05).Kaplan-Meier analysis revealed that there was no statistically significant difference in 14-day survival rate between the two groups(P>0.05). Conclusion Chinese Rhubarb can down-regulate TM and t-PAIC levels and improve vascular endothelial cell function in patients with sepsis.

Objective To explore the feasibility of rapid saline infusion ultrasound imaging for the assessment of the central venous catheter tip location. Methods A total of 83 critically ill adult patients with indications for central venous catheterization who were admitted to Peking University People's Hospital from July 2020 to July 2021 were selected. Cardiac ultrasonography was used to observe the turbulent flow imaging formed after rapid injection of normal saline into the central venous catheter to quickly determine the exact position of the catheter tip, and compared with the results of bedside chest X-ray to evaluate the method of rapid injection of normal saline effectiveness. Results The results of judging the position of the tip of the central venous catheter by the rapid perfusion ultrasound imaging of normal saline and bedside chest X-ray were basically consistent (Kappa=0.917, P<0.05). The rapid saline infusion ultrasound imaging had a sensitivity of 100.0%(95%CI 94.0%-100%)and specificity of 85.7%(95%CI 42.0%-99.2%). It took 77.5 (69.5, 85.5) minutes to determine the catheter position by chest X-ray, which was significantly longer than that of normal saline perfusion ultrasound imaging [6.4 (5.8, 6.9) minutes], and the difference was statistically significant (P<0.05). Conclusion The rapid saline infusion ultrasound imaging can effectively determine the tip position of the central venous catheter and the diagnosis time is shorter than that of the bedside chest X-ray examination.

Long non-coding RNAs (lncRNAs) are composed of a group of RNAs with more than 200 nucleotides but lacking protein coding functions. It has been gradually confirmed that it plays an important role of carcinogenic or tumor suppressor genes in the development and progression of human cancer. Small nucleolar RNA host gene 17 (SNHG17) is a lncRNA located on chromosome 20q11.23. In recent years, a large number of studies have explored the potential regulatory roles of SNHG17 in a variety of human cancers [such as oral squamous cell carcinoma, gastric cancer, hepatocellular carcinom, pancreatic cancer,colorectal cancer, lung cancer, breast cancer, prostate cancer, ovarian cancer, glioma, melanoma and osteosarcoma, etc.] progression,and high expression is usually closely related to the clinicopathological characteristics of tumor patients. In addition, it can promote the proliferation and metastasis of tumor cells, while inhibiting apoptosis. Therefore, SNHG17 is considered as a potential tumor biomarker and therapeutic target. This review focuses on the relevant research reports of SNHG17 in human cancers at home and abroad in recent years, focusing on the latest insights into the expression, functional role and molecular mechanism of SNHG17 in human malignant tumors, in order to provide a theoretical basis for clinical cancer treatment.

Helicobacter pylori (Hp) infection is a common chronic bacterial infection in humans, which is significantly associated with a variety of gastrointestinal diseases. Traditionally, Hp eradication is based on one type of proton pump inhibitors(PPIs) combined with two types of antibiotics. PPIs could increase the pH value in the stomach to strengthen the bactericidal or antibacterial effects of antibiotics. Vonoprazan is a new drug with a stronger acid-suppressing effect compared to PPIs. Vonoprazan-based regimens are not inferior to PPIs-based regimens for eradicating Hp and are well tolerated. This article aims to summarize the effects of vonoprazan-based treatment strategy for Hp eradication, including vonoprazan-based first-line, second-line, and third-line regimens, vonoprazan-based regimens on penicillin-allergic and clarithromycin-resistant patients, vonoprazan-based dual and first-line triple regimens, and 10-14 d vonoprazan-based regimens.