OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G₁-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation ; Matrix Metalloproteinase 9 ; Molecular Docking Simulation ; Cell Cycle ; ErbB Receptors ; Apoptosis ; Colorectal Neoplasms/pathology* ; Cell Line, Tumor

The non-randomized controlled study design was adopted. A total of 90 patients with knee osteoarthritis treated in Beijing Yuetan Community Health Service Center from September 2021 to August 2022 were enrolled in the study, including 45 patients received patellar loosening and then the quadriceps femoris pain point release (successive group) and remaining 45 patients received two manipulations simultaneously (simultaneous group). Patients were treated 3 times in a week, and each time received 5 groups of manipulation. The Visual Analogue Scale (VAS) and Lysholm scores were measured before treatment, immediately after treatment and 3 months after treatment. There was no exfoliation and no adverse events in both groups. There were no significant differences in VAS and Lysholm scores between the two groups before treatment ( P>0.05). Immediately after treatment, the VAS pain score in the simultaneous group was lower than that in the successive group ((3.36±1.12) vs.(2.24±0.93), P<0.01), while the Lysholm score in the simultaneous group was higher than that in the successive group ((89.76±6.61) vs.(74.07±16.80), P<0.01); the proportion of VAS score as“painless/mild pain”(88.9% (40/45) vs.64.4% (29/45), P<0.01) and Lysholm score as “excellent/good”(91.1% (41/45) vs. 44.4% (20/45), P<0.01) in the simultaneous group was significantly higher than that in the successive groups. At 3 months after treatment, there were still significant differences in VAS and Lysholm scores between the two groups. The simultaneous manipulations of patellar loosening and quadriceps femoris pain point release can better relieve the pain of patients with knee osteoarthritis.

ObjectiveTo explore the mechanism of Qigesan （QGS） in intervening in the migration and invasion of esophageal carcinoma TE-1 cells. MethodMicroarray technology was used to screen differentially expressed genes （DEGs） in the normal group and the QGS group， and the ontological functions and signaling pathways of DEGs were analyzed. The thiazolyl tetrazolium （MTT） assay was used to detect the effect of QGS on the viability of TE-1 cells. In the subsequent experiments for verification， a blank group， a transforming growth factor-β₁ （TGF-β₁） group， a TGF-β₁ + QGS group， and a TGF-β₁ + SB431542 group were set up. The cell morphology in each experimental group was observed by microscopy. The migration and invasion abilities of cells were detected by wound healing assay， and the mRNA expression levels of E-Cadherin， vimentin， Smad2， and Smad7 were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of E-Cadherin， vimentin， p-Smad2/3， Smad2/3， and Smad7 was detected by Western blot. ResultThere were 1 487 DEGs between the QGS group and the blank group， including 1 080 down-regulated ones （accounting for 72.63%） and 407 up-regulated ones. The down-regulated genes were mainly involved in biological processes such as cytoskeletal protein binding， ATP binding， adenylate nucleotide binding， and adenylate ribonucleotide binding， and the involved Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways included TGF-β signaling pathway， cell cycle， extracellular matrix-receptor interaction protein， tumor pathways， and oocyte meiosis. The up-regulated genes were mainly involved in RNA binding， DNA binding， transcriptional regulator activity， transcriptional activator activity， and nucleotide binding， and the KEGG pathways involved mainly included mitogen-activated protein kinase （MAPK） signaling pathway， bladder cancer， renal cell carcinoma， cancer pathways， and p53 signaling pathway. Compared with the blank group， the inhibition rate of cell viability of TE-1 cells increased after QGS （20， 30， 40， 60， 80 mg·L^-1） intervention for 12， 24， 36， 48， 60 h （P<0.05）， and the inhibition rate was time- and dose-dependent. Compared with the blank group， the TGF-β₁ group showed lengthened cells with fibroblast phenotype. Compared with the TGF-β₁ group， the TGF-β₁ + QGS group showed shortened cells with normal morphology and epithelial phenotype. The cell morphology in the TGF-β₁ + SB431542 group was similar to that of the TGF-β₁ + QGS group. Compared with the blank group， the TGF-β₁ group showed potentiated ability of cell migration and invasion （P<0.05）. Compared with the TGF-β₁ group， the TGF-β₁ + QGS group and the TGF-β₁ + SB431542 group showed inhibited and weakened migration and invasion abilities of cells （P<0.05）. However， there was no significant difference in migration and invasion abilities between the TGF-β₁ + QGS group and the TGF-β₁ + SB431542 group. The mRNA expression levels of vimentin and Smad2 in the TGF-β₁ group were higher （P<0.05）， and the mRNA expression levels of E-Cadherin and Smad7 were lower （P<0.05） than those in the blank group. Compared with the TGF-β₁ group， the TGF-β₁ + QGS group and the TGF-β₁+ SB431542 group exhibited decreased expression levels of vimentin and Smad2 mRNA （P<0.05）， and elevated expression levels of E-Cadherin and Smad7 mRNA （P<0.05）. Compared with the blank group， the TGF-β₁ group showed up-regulated protein expression levels of vimentin， p-Smad2/3， and Smad2/3 （P<0.05）， and reduced protein expression levels of E-Cadherin and Smad7 （P<0.05）. Compared with the TGF-β₁ group， the TGF-β₁ + QGS group and the TGF-β₁ + SB431542 group displayed decreased protein expression levels of vimentin， p-Smad2/3， and Smad2/3 （P<0.05）， and increased protein expression levels of E-Cadherin and Smad7 （P<0.05）. ConclusionThe ethyl acetate extract of QGS inhibits the epithelial-mesenchymal transition （EMT） of TE-1 cells through the TGF-β₁ pathway to reduce the migration and invasion of TE-1 cells.

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Objective To investigate the dietary intake of preschool children in Northwest China, and provide scientific basis for studying the dietary patterns and characteristics of preschool children and formulating targeted dietary interventions. Methods Using the self-designed ^“Semi-quantitative Food Frequency Questionnaire for Preschool Children in Northwest China^“, a convenient sampling method was used to investigate the dietary intake of children aged 3 to 7 years in Northwest China. The factor analysis combined with the cluster method was used to extract the dietary pattern. Results Through factor analysis of the average daily food intake of preschool children, the results show that the KMO test value was 0.82, Bartlett’s test value was 4 528.97, and the associated probability was <0.001, so factor analysis can be performed. In order to obtain more typical factor components so that the results were easier to explain, under the guidance of nutrition experts, the first 4 common factors were finally retained for analysis, and the cumulative variance contribution rate was 62.17%. On this basis, the number of clusters was 4, and the K-means cluster analysis method was used to cluster the factor scores of various foods for preschool children. According to the proportions of various foods and the characteristics of the foods, The dietary patterns of preschool children can be divided into staple food-based dietary patterns, high-protein dietary patterns, healthy dietary patterns, and high-sugar dietary patterns. Conclusion Using factor analysis method, the scores of each food factor of preschool children were continuous variables, and the results were highly repeatable, and subsequent analysis can be carried out. The factor analysis combined with cluster analysis method extracting the dietary pattern of preschool children that had certain degree of science. According to the characteristics of the four dietary patterns extracted in this study, children's dietary interventions can be targeted to promote children's physical and mental health.

Objective:To retrospectively analyze the efficacy and safety of dupilumab in the treatment of bullous pemphigoid (BP) .Methods:Clinical data were collected from BP patients who received injections of dupilumab at an initial dose of 600 mg followed by an every-2-week regimen at a dose of 300 mg (the frequency of injections could be increased if necessary) in Department of Dermatology, Peking University First Hospital from October 2020 to October 2021, and their clinical manifestations and changes in laboratory indices were analyzed.Results:A total of 21 BP patients treated with dupilumab were included in this study. Nineteen (90.5%) patients achieved complete or marked disease control after 2-week treatment with dupilumab; 12 patients were followed up for 16 weeks, and all maintained complete disease control at 16 weeks. All patients had a bullous pemphigoid disease area index (BPDAI) score of 122.5 ± 51.1 points at baseline, which decreased to 30.6 ± 27.4 points after 2-week treatment with dupilumab ( t = 8.53, P < 0.001) , and continued to decrease to 12.7 ± 9.1 points after 4-week treatment ( t = 9.73, P < 0.001) . Pruritus was markedly relieved in all the 21 patients within 4-week treatment with dupilumab. Among 10 patients with elevated eosinophil counts at baseline, the eosinophil counts markedly decreased in 9 after treatment. The serum IgE level was elevated in 7 patients at baseline, which markedly decreased in 6 after treatment. Viral conjunctivitis occurred in 1 (4.8%) patient, and no adverse reactions were observed in other patients. Conclusion:Dupilumab is effective in the control of BP and relief of pruritus, with a favorable safety profile.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.