Objective To explore the potential mechanisms of hypoxic adaptive metabolic changes in the kidneys of plateau pikas at different altitudes using non-targeted metabolomics analysis via ultra-high-performance liquid chromatography coupled with quadrupole electrostatic field orbital trap-mass spectrometry (UHPLC-QE-MS). Methods 10 plateau pikas were captured at an altitude of 4 360 m in Xingxiuhai area, Maduo County, Guoluo Tibetan Autonomous Prefecture, Qinghai Province (MD group), and 10 plateau pikas were captured at an altitude of 2 900 m in Menyuan area, Haibei Tibetan Autonomous Prefecture, Qinghai Province (MY group). After anesthesia, serum samples were collected, and kidney samples were collected after euthanasia. General physiological and biochemical indicators were measured and metabolomics analysis was performed. Part of the serum samples was used for hematology analysis, another part for blood gas analysis, and the remaining part for biochemical indicator detection. Metabolites were extracted from the kidney tissue samples and then analyzed using UHPLC-QE-MS. Differential metabolites were analyzed using metabolomics principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), with screening criteria set as variable importance in projection (VIP)>1.5 and fold change (FC)>1.5, or VIP>1.5 and FC<1/1.5. Correlation analysis heatmaps, significance analysis volcano plots, signaling pathway recognition bubble charts, and rectangular graphs were used for the analysis of differential metabolites and related signaling pathways. Results The red blood cell count, glucose, urea nitrogen, uric acid, and homocysteine levels in the MD group plateau pikas were higher than those in the MY group, while hemoglobin, hematocrit, creatinine, and carbon dioxide combining power were lower than those in the MY group. This indicated a significant difference in the blood oxygen-carrying capacity of plateau pikas at different altitudes. The principal component pattern recognition analyses, and OPLS-DA permutation test showed that the kidney metabolites of the MD and MY groups of plateau pikas had distinct clustering distributions (R²Y=0.930, Q²=0.655). According to the screening criteria and database comparison, 46 differential metabolites were identified in the kidneys of plateau pikas at different altitudes. In the MD group of plateau pikas, the expression levels of bufadienolide, adenosine, adenine, diosgenin, berberine chloride, carnosol, and astaxanthin were significantly increased (VIP>1.5, P<0.05), while the levels of arachidonic acid, histamine, and coumarin were significantly decreased (VIP>1.5, P<0.05). The analysis of related signaling pathways showed that the biosynthetic pathways of valine, leucine, and isoleucine had the largest impact factors (P<0.05), while the biosynthetic pathways of pantothenate and coenzyme A showed the most significant enrichment (P<0.05). Conclusion The differential metabolites of amino acids, pantothenate, and coenzyme A pathways in the kidneys of plateau pikas at different altitudes may be involved in the metabolic mechanisms of plateau pikas' hypoxia adaptation in high-altitude environments.

Objective This article aims to investigate the association between hypertension and the risk of GSD by conducting a national multicenter study,a systematic review,and a meta-analysis.Methods The study was conducted in three stages.In the first stage,subjects were recruited for health examination in four hospitals in Chengdu,Tianjin,Beijing,and Chongqing,China,from 2015 to 2020,and the multivariate logistic regression analysis was used to investigate the association between hypertension and the risk of GSD in each center.In the second stage,Embase,PubMed,Wanfang Data,VIP,and CNKI databases were searched for related studies published up to May 2021,and a meta-analysis was conducted to further verify such association.In the third stage,the random effects model was used for pooled analysis of the results of the multicenter cross-sectional study and the findings of previous literature.Results A total of 633 948 participants were enrolled in the cross-sectional study,and the prevalence rate of GSD was 7.844%.The multivariate logistic regression analysis showed that hypertension was positively associated with the risk of GSD(P＜0.05).Subgroup analysis showed that there was no significant difference in the association between hypertension and GSD between individuals with different sexes,ages,and subtypes of GSD.A total of 80 articles were included in the systematic review and the meta-analysis,and the results showed that the risk of GSD was increased by 1.022 times for every 10 mmHg increase in diastolic pressure and 1.014 times for every 10 mmHg increase in systolic pressure.Conclusion Hypertension significantly increases the risk of GSD,and the findings of this study will provide a basis for the etiology of GSD and the identification of high-risk groups.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective:To investigate the impact of exosomes and microRNA (miRNA) from placental mesenchymal stem cells on chemotherapy-damaged ovarian granulosa cells.Methods:Various public databases were searched for miRNA targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN) gene. After miRNA transfection into human ovarian granulosa cells, cell growth and expressions of the target miRNA and PTEN were detected. Cisplatin was utilized to induce damage to human ovarian granulosa cells, which were subsequently co-cultured with human placental mesenchymal stem cells and exosomes generated from mesenchymal stem cells, then apoptosis and expressions of PTEN and the target miRNA were detected.Results:After analyzing several databases, miRNA 139-5p (miR-139-5p) was chosen as the target miRNA for this research. Transfection of miR-139-5p mimics into human ovarian granulosa cells elevated miR-139-5p expression level (9 882.080±1 049.130), reduced PTEN protein expression level (0.78±0.11), and increased cell proliferation absorbance (0.85±0.07). Cisplatin treatment severely damaged human ovarian granulosa cells and increased apoptosis, cisplatin-treated cells had a higher apoptosis ratio compared to untreated cells [ (41.9±1.0)% vs (5.0±0.3)%, P<0.001]. In damaged human ovarian granulosa cells, co-cultured with human placental mesenchymal stem cells and exosomes increased miR-139-5p expression levels (1.31±0.04 and 1.20±0.03, respectively) and decreased apoptosis ratios [(20.0±0.4)% and (22.3±1.1)%, respectively]. Conclusion:Placental mesenchymal stem cell-derived exosomes repair damages of cisplatin-induced ovarian granulosa cell and could target PTEN gene through miR-139-5p, which might be a potential option for the treatment of chemotherapy-induced ovarian dysfunction.

Objective: To observe the effects of electroacupuncture (EA) at Neiguan (PC6) on arrhythmia during acute myocardial ischemia-reperfusion and the expression of connexin 43 (Cx43) in rats. Methods: A total of 40 Sprague-Dawley male rats were used. Ten rats were randomly selected as the blank group, and the remaining 30 rats were randomly divided into a model group and an EA group, with 15 rats in each group. Before modeling, rats in the EA group received one session of EA intervention at bilateral Neiguan (PC6) for 30 min; the other groups were treated with the same grasping and anesthesia for 30 min without intervention. PowerLab physiological recorder was used to record electrocardiograph within 30 min of infarction. After the experiment, cardiac tissue and serum were collected from rats. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of myocardial tissue in the ventricular infarction area of rats in each group. The expression of Cx43 protein in the myocardium of each group was detected by Western blotting (WB). Enzyme-linked immunosorbent assay (ELISA) was used to determine the activity of Na+-K+-ATPase in myocardial tissue and the serum content of endogenous digitalis-like factor (EDLF) in rats. Results: There was no statistical difference in arrhythmia score between the EA group and the model group, but the total duration and average duration of arrhythmia in the EA group were decreased (P<0.01). HE staining showed that compared with the blank group, myocardial cells in the model group were disorganized and seriously damaged. The pathological changes in the EA group were similar to those in the model group, but the damage was relatively minor. The results of WB showed that compared with the blank group, the Cx43 expression in myocardial tissue of the model group was decreased (P<0.01); compared with the model group, the Cx43 expression in the EA group was increased (P<0.01); compared with the blank group, the Na+-K+-ATPase activity in myocardial tissue of the model group was significantly decreased (P<0.01); compared with the model group, the Na+-K+-ATPase activity in the EA group was increased (P<0.01). ELISA results showed that compared with the blank group, the serum EDLF content in the model group was significantly increased (P<0.01); compared with the model group, the EDLF content in the EA group was decreased (P<0.01). Conclusion: EA at Neiguan (PC6) can delay and reduce the onset of arrhythmia during myocardial infarction in the rat model of myocardial ischemia-reperfusion. Its mechanism of action may be related to the regulation of the Cx43 expression in myocardial tissue, improvement of the activity of Na+-K+-ATPase in myocardial tissue, and increase in the content of serum EDLF.

Objective:To study the effects of a simulated plateau environment on fracture healing in rats.Methods:A rat model of mid-femoral fracture was established by hacksaw truncation and intramedullary fixation with Kirschner wires in 60 male Wistar rats which were divide into 2 groups ( n=30) by the random number table method. The rats in the control group were raised in the animal experiment center of The 940 Hospital of Joint Logistic Support Force of Chinese PLA at an altitude of 1,400 m, while the rats in the plateau group were placed in an animal experimental cabin in a simulated plateau environment at a simulated altitude of 5,000 m. The body weight was weighed once a week and X-ray films were taken every 2 weeks. Blood samples were collected after 4 weeks for detection of biochemical indicators of bone metabolism. After 8 weeks, the femurs of the surgical side were taken for bone biomechanical detection and the bone mineral density of the healthy side was detected. After 4 and 8 weeks, the femurs of the surgical side were taken for in vitro Micro-CT scanning and angiography detection. After 1, 2, 4 and 8 weeks, the femurs of the surgical side were taken for bone histopathologic detection. Results:During the entire experiment, no rats in the control group died while the mortality rate of the rats in the plateau group was as high as 26.7% (8/30). In the plateau group, some organs were pathologically damaged in the rats, fracture union was delayed, and the callus differentiated and matured slowly with the chondrocytes still dominant at the 8th week. The bone mineral density and the maximum load of the femur in the plateau group were significantly lower than those in the control group ( P< 0.05). Angiography showed that the rats in the plateau group had microvascular proliferation which did not penetrate the fracture end at the 8th week. The bone formation indexes like osteocalcin, procollagen type Ⅰ N-terminal propeptide (PⅠNP), and osteoprotegerin of the rats in the plateau group were significantly lower than those in the control group at the 4th week ( P<0.05). The bone resorption indexes like tartrate resistant acid phosphatase 5b (TRACP-5b) and receptor activator for nuclear factor-κB ligand (RANKL) in the plateau group were significantly higher than those in the control group ( P<0.05). Conclusion:A simulated plateau environment at an altitude of 5,000 m may lead to delayed fracture healing in rats.

Objective: To detect the differences in the expression of Yes-associated protein(YAP) in non-cardia gastric cancer and normal gastric tissue and analyze the associations between single nucleotide polymorphisms(SNP) in the YAP gene andits protein expression,and to preliminarily discuss the correlationbetween YAP and the development of non-cardia gastric cancer,so as to provide new ideas for the prevention and treatment of non-cardia gastric cancer. Methods: 126 casesofnon-cardia gastric cancer tissues and 104 cases of paracancerous normal tissues were collected and set as case group and control group,respectively. Immunohistochemical SP assay was used to detect the expression of YAP in non-cardia gastric cancer tissues and adjacent normal tissues. Taqman method was used for genotyping. The unconditional logistic regression method was used to calculate the odds ratio(OR) and its 95%confidence interval(CI) to detect the associations between YAP SNPs and the expression of YAP protein under Codominant,Dominant,Overdominant,Recessive,and Log-additive genetic models. Results: The expression of YAP protein in non-cardia gastric cancer tissues was significantly higher than that in normal gastric tissues(P<0. 001).The expression level of YAP protein was negatively correlated with the degree of tumor differentiation(P<0. 05).There was no correlationbetween the expression level of YAP protein and gender,age,lymph node metastasis and tumor size respectively(P>0. 05). No associations were found between SNP rs11225163 and rs1820453 and the expression of YAP protein under Codominant,Dominant,Overdominant,Recessive and Log-additive genetic models.Haplotype was constructed by Haploview 4. 2 software,and the association between haplotype and YAP protein expression was analyzed. Conclusion YAP may be involved in the development of non-cardia gastric cancer.

2019 novel coronavirus(2019-nCoV) outbreak is one of the public health emergency of international concern.Since the 2019-nCoV outbreak, China has been adopting strict prevention and control measures, and has achieved remarkable results in the initial stage of prevention and control.However, some imported cases and sporadic regional cases have been found, and even short-term regional epidemics have occurred, indicating that the preventing and control against the epidemic remains grim.With the change of the incidence proportion and the number of cases in children under 18 years old, some new special symptoms and complications have appeared in children patients.In addition, with the occurrence of virus mutation, it has not only attracted attention from all parties, but also proposed a new topic for the prevention and treatment of 2019-nCoV infection in children of China.Based on the second edition, the present consensus further summarizes the clinical characteristics and experience of children′s cases, and puts forward recommendations on the diagnostic criteria, laboratory examination, treatment, prevention and control of children′s cases for providing reference for further guidance of treatment of 2019-nCoV infection in children.

Objective:To explore the preventive measures of nasal pressure injury in patients with preserved nasal endotracheal intubation after oral and maxillofacial neoplasms resection and simultaneous free tissue flap transplantation.Methods:Using the convenient sampling method, a total of 520 patients who underwent oral and maxillofacial neoplasms resection and simultaneous free tissue flap transplantation in Peking University Hospital of Stomatology were selected as the research objects from August 2018 to December 2019. According to the random number table method, they were divided into the experimental group and the control group. Patients in the control group received routine care, while in the experimental group, silk surgical tape was used to re-fix the endotracheal intubation tube away from the original position, and the special-shaped inflatable balloon was used to support the remote end of the tube. The incidence of nasal pressure injury, medical adhesive-related skin injury (MARSI) and the occurrence of complications caused by the fixation of tracheal intubation of patients were compared between the two groups. In the end, 246 patients in the experimental group and 248 patients in the control group completed the study.Results:No stage 3 or above nasal pressure injury occurred in the two groups. The incidence of nasal pressure injury related to nasotracheal tube in the experimental group was 2.85% (7/246) , lower than 12.10% (30/248) in the control group (χ 2=15.254, P<0.001) . There was no statistically significant difference in the incidence of MARSI of patients between the two groups ( P>0.05) . No complications caused by endotracheal intubation fixation occurred in both groups. Conclusions:The use of silk surgical tape to re-fix the endotracheal intubation and the combination of special inflatable balloon to support the end of the endotracheal intubation can prevent nasal pressure injury, and the safety is better.