Synthesis and evaluation for anti-HCoV-OC43 activity of novel aloperine derivatives with different core structures / 药学学报

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC50 values of 3.77 μmol·L-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Clinical study on the treatment of gastrointestinal neurosis with insomnia by combination of "stomach ten acupuncture" and domperidone tablets / 国际中医中药杂志

Objective:To study on the effect of "stomach ten acupuncture" combined with domperidone tablets on clinical symptoms and sleep quality of gastrointestinal neurosis patients with insomnia based on the theory of "stomach harmonious leading to restless".Methods:Randomized controlled trial. From March 2020 to March 2021, 98 patients with gastrointestinal neurosis and insomnia in our hospital who met the inclusion criteria were randomly divided into two groups, with 49 patients in each group. The control group took domperidone tablets orally, and the observation group was treated with "stomach ten acupuncture" on the basis of the control group. Both groups were treated for 8 weeks. Before and after treatment, TCM syndromes were scored, the severity of gastrointestinal symptoms was assessed with Gastrointestinal Symptom Rating Scale (GSRS), anxiety and depression were assessed with Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD), and sleep quality was assessed with Pittsburgh Sleep Quality Index Scale (PSQI).Results:After treatment, the scores and total scores of epigastric pain, belching, abdominal distension, anorexia, noisy acid regurgitation, tiredness and asthenia, constipation and loose stools in the observation group were significantly lower than those in the control group ( t values were 19.61, 19.30, 23.10, 22.05, 20.43, 21.81, 20.51, 16.38, respectively, P<0.01); the scores and total scores of typical symptoms, abdominal pain symptoms, reflux symptoms, diarrhea symptoms, constipation symptoms were significantly lower than those in the control group ( t values were 10.10, 11.14, 11.04, 9.31, 11.24, 5.30, respectively, P<0.01); HAMA and HAMD scores were significantly lower than those in the control group ( t values were 6.96 and 6.85, respectively, P<0.01). The scores of time to fall asleep (1.15 ± 0.56 vs. 2.11 ± 0.75, t=7.18), time to sleep (0.92 ± 0.63 vs. 1.52 ± 1.12, t=3.27), sleep quality (1.02 ± 0.66 vs. 1.96 ± 0.80, t=6.35), sleep efficiency (0.86 ± 0.62 vs. 1.68 ± 0.85, t=5.46), sleep disorders (0.92 ± 0.36 vs. 1.48 ± 0.55, t=5.96), daytime dysfunction (0.96 ± 0.42 vs. 1.97 ± 0.87, t=7.32), hypnotics (0.98 ± 0.45 vs. 1.81 ± 0.62, t=7.58) and total scores (6.85 ± 1.47 vs. 12.73 ± 2.95, t=12.49) were significantly lower than those in the control group ( P<0.01). Conclusion:The "stomach ten acupuncture" combined with domperidone tablets can improve the clinical symptoms and sleep quality of gastrointestinal neurosis patients with insomnia.

Analysis of Cesarean Section Rates and its Indications Using Robson's Classification at a Tertiary Care Hospital, Manipur

Context: The World Health Organization proposed the Robson’s classification system as a global standard for assessing and comparing cesarean section (CS) rates within health-care facilities over time and between facilities. Aims: This study aims to assess the frequency and indications of CS and to identify the groups within the obstetric population contributing to CS using Robson’s classification. Settings and Design: A retrospective chart review was conducted in a Tertiary Care Teaching Hospital in Imphal, Manipur. Methods: All women who delivered between January and December 2019 were classified using the Robson’s Ten Group Classification System. The overall CS rate and the CS rate in each Robson’s group were calculated. The indications for CS were also recorded. Statistical Analysis Used: Descriptive statistics, such as frequency, percentage, mean, and standard deviation, was used. Results: A total of 10,282 births were reported. The overall CS rate was 35.2%. Group 3 (multiparous women without previous CS in spontaneous labor) (27.6%) and Group 1 (nulliparous women in spontaneous labor) (23.7%) contributed to most of the obstetric populations. The majority of CS belonged to the women in Group 5 (multiparous women with previous lower segment CS) (11%), followed by Group 2 (nulliparous women with labor induced or prelabor CS) (8.6%) and Group 4 (multiparous women without previous CS were induced or taken for prelabor CS) (5.5%). Conclusions: The study revealed that Groups 5, 2, and 4 contributed to the high CS rate. Efforts to reduce the overall CS rate should be directed at increasing vaginal births after CS, performing effective pelvic examinations, and encouraging obstetricians to perform versions when indicated.

ALLOPURINOL INDUCED ADVERSE DRUG REACTIONS: CASE SERIES

Allopurinol is widely used drug for patients of hyperuricemia and gout. The few adverse drug reactions related to allopurinol are diarrhea, fever, hepatotoxicity, Steven Johnson Syndrome- Toxic Epidermal Necrolysis (SJS-TEN), congestive heart failure and renal failure. In this article we have described eleven cases to evaluate the causality, cause and management of this syndrome. In this study eleven retrospective cases were selected from the ADR reports. The full details of the cases were collected from Christian Medical College from the period of 2012 to 2016. Causality was established using Naranjo scale and classi?cation was done based on severity and resolution of ADR. It was observed that cases presented with mild to severe reactions of allopurinol, which is the suspected offending agent. Cases were resolved with supportive treatment while ?ve case had a prolong hospitalization and two cases had a life threatening drug reaction. Early detection and management of this severe form of systemic reaction is very important for better will be the prognosis.

The effect of "ten needles in the stomach" treatment on sleep perception for the patients with spleen-gastric damp-heat insomnia based on the theory of "stomach upset, sleep restlessness" / 国际中医中药杂志

Objective:To explore the effect of "ten needles in the stomach" on sleep perception of patients with spleen-gastric damp-heat insomnia based on the theory of "stomach discord, then sleep restlessness", to provide references for clinical diagnosis and treatment.Methods:The study subjects were 300 patients with insomnia from the sleep department and outpatient department of Shijiazhuang Traditional Chinese Medicine Hospital. According to the random number method, they were divided into the stomach ten needle group, the diazepam group, and the stomach ten needle plus diazepam group, with 100 in each group. Among them, the stomach ten needles group received "stomach ten needles" acupuncture treatment, the diazepam group was given diazepam therapy, and the stomach ten needles plus diazepam group was given diazepam combined with "stomach ten needles" acupuncture treatment. The Pittsburgh Sleep Quality Index (PSQI) scores, the self-rating disease symptom scale (SCL-90) scores, nighttime polysomnography (PSG) monitoring indicators, and the mean sleep latency (MSL) values were compared before and after treatment in the three groups. The difference in clinical efficacy between the two groups were observed.Results:The total effective rate was 94.0% (94/100) in the combined group, 77.0% (77/100) in the diazepam group, and 85.0% (85/100) in the stomach ten needle group. There were significant differences among the three groups ( χ2=11.56, P<0.01). After treatment, the daytime dysfunction, hypnotic drugs, sleep disturbance, sleep efficiency, sleep time, sleep time, sleep quality score and total score of the combined group were significantly lower than those in the diazepam group and the stomach ten needle group ( F=5.70, 3.65, 5.23, 6.37, 3.66, 6.19, 7.54, 6.40, all Ps<0.01); The scores of SCL-90 and MSL were significantly lower than those in the diazepam group and stomach ten needle group ( F=8.97, 7.53, all Ps<0.01). In the combined group, NWAK [(1.36 ± 0.87) times vs. (2.69 ± 1.15) times, (2.11 ± 1.05) times, F=5.88], SOL [(13.62 ± 5.85) min vs. (25.06 ± 9.42) min, (19.78 ± 7.63) min, F=6.49], N1/TST [(5.69 ± 1.09)% vs. (12.65 ± 2.58)%, (8.49 ± 2.45)%, F=5.13], N2/TST [(51.07 ± 10 2.06)% vs. (58.36 ± 2.18)%, (55.61 ± 2.04)%, F=9.86] were significantly lower than those in the diazepam group and stomach ten needle group ( P<0.01), SE [(90.33 ± 2.89)% vs. (85.39 ± 2.75)%, (87.53 ± 2.69)%, F=8.36], TST [(449.32 ± 23.65) min vs. (421.66 ± 25.33) min, (431.26 ± 25.98) min, F=8.26], REM/TST [(23.87 ± 4.52)% vs. (14.52 ± 3.87)%, (18.36 ± 3.25)%, F=5.34], N3/TST [(18.69 ± 2.02)% vs. (10.31 ± 1.64)%, (14.89 ± 1.74)%, F=7.69] were significantly higher than those in the diazepam group and stomach ten needle group ( P<0.01). Conclusion:Based on the "stomach discord, sleep restlessness" theory, the ten needles on the stomach can treat insomnia and improve psychological state and sleep quality, with the functions of clearing the damp and heat of the middle joker, regulating the lifting and lowering of qi in the middle.

Exploration on the spectrum of disease of Experienced Ten Acupoints based on bibliometrics / 国际中医中药杂志

Objective:We aimed to analyze the spectrum of diseases of Experienced Ten Acupoints in clinical studies, in order to provide reference for further clinical trials.Methods:The Chinese academic journals full-text database (CNKI),Chinese science and technology journals full-text database (VIP),Wanfang database and Chinese biomedical database (SinoMed), PubMed, Cochrane Library and Web of Science Database were searched from the incecption to October, 2021. The quantitative analyses were conducted on the characteristics of the clinical studies, including years of publication, journals, affiliations of authors, interventions, diseases, types of studies, evaluation of efficacy, rate of citations.Results:A total of 81 articles were included in 44 journals. The majority types of studies were RCTs, the main intervention was acupuncture as well as acupuncture combined with Traditional Chinese Medicine or medicine. For types of diseases, digestive system diseases account for the major part (66.67%), followed by nervous system diseases (17.28%).Conclusions:The studies associated with Experienced Ten Acupoints were relatively few, the corresponding spectrum of diseases was in limit range, and experimental studies lacks. This study suggested that the clinicians should pay attention to the classical acupoints prescriptions, and the research progress of clinical trials should be more standardized.

Role and mechanism of miRNA-29a/PTEN pathway in neuronal network damage caused by aluminum / 环境与职业医学

Background Aluminum can cause synaptic plasticity damage in the hippocampus, probably due to blocked interneuronal signal transmission. MicroRNA-29a (miR-29a) can target phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression and participate in the generation of neuronal networks, and may be involved in the effect of aluminum on the electrical activity of neuronal networks. Objective To study the role and mechanism of miR-29a-targeted PTEN in aluminum-induced neuronal network injury in primary hippocampal neurons of ICR mice treated with maltol aluminum [Al(mal)3] in vitro. Methods Primary hippocampal neurons of ICR mice born within 24 h were cultured in vitro. The purity of neurons was determined by labeling neuron-specific microtubule-associated protein 2 (MAP2) by immunofluorescence staining on day six of the culture; neurons were treated with different concentrations of Al(mal)3, and divided into a control group, and 10, 20, and 40 μmol·L−1 Al(mal)3 groups, and neuronal cell viability was detected by CCK-8 method. Al(mal)3 at 20 μmol·L−1 was selected for subsequent experiments to establish a neuronal network injury model for intervention. The lentivirus infection method was used to transfect miR-29a into neurons, which were divided into mNG, mNG+20 μmol·L−1 Al(mal)3, miR-29a, and miR-29a+20 μmol·L−1 Al(mal)3 groups, and micro-electrode array (MEA) was used to analyze the firing of neuronal network. The expressions of miR-29a and PTEN mRNA in each group were detected by real-time PCR (RT-PCR), and the expression of PTEN protein in each group was detected by Western blotting. Results The purity of primary mouse hippocampal neurons was greater than 90%, and the viability of the neurons was above 80% in all groups. At 48 h of the designed Al(mal)3 treatments, the changes in spike frequency, burst frequency, network burst frequency, and synchrony index of neurons cultivated on MEA plates in the control group were 207.56%±38.70%, 73.19%±46.43%, 75.42%±33.04%, and 117.13%±15.54%, respectively; the Al(mal)3 groups’ neuronal network electrical activity showed a decreasing trend. Compared with the control group, the spike frequency, burst frequency, network burst frequency, and synchrony index of the 20 and 40 μmol·L−1 Al(mal)3 groups significantly decreased (The changes were 171.70%±28.08%, 49.20%±23.23%, 50.20%±18.18%, and 85.45%±20.30%; 150.68%±26.15%, 43.43%±15.54%, 52.05%±26.31%, and 26.80%±8.29%, respectively, P < 0.05). Compared with the control group (1.00), the miR-29a relative expression levels were significantly decreased in the 20 μmol·L−1 Al(mal)3 group (0.74±0.09) and the 40 μmol·L−1 Al(mal)3 group (0.62±0.12) (P < 0.05); the relative expression levels of PTEN mRNA were significantly increased in the 20 μmol·L−1 Al(mal)3 group (1.32±0.12) and the 40 μmol·L−1 Al(mal)3 group (1.48±0.11) (P < 0.05); the PTEN protein relative expression levels (1.29±0.12 and 1.82±0.10, respectively) were also significantly increased (P < 0.05). By overexpressing miR-29a in mouse primary hippocampal neurons, the spike frequency, burst frequency, and network burst frequency were significantly higher in the miR-29a group compared with the mNG group (The changes were 252.80%±62.03%, 171.65%±56.30%, and 197.75%±27.12%, respectively, P<0.05). The mNG+20 μmol·L−1 Al(mal)3 group showed a significant decrease in all indicators of neuronal network electrical activity (The changes were 123.28%±47.31%, 66.62%±31.53%, 70.60%±12.48%, and 52.86%±20.26%, respectively, P < 0.05). Compared with the mNG+20 μmol·L−1 Al(mal)3 group, the electrical activity indicators of neuronal network were significantly higher in the miR-29a+20 μmol·L−1 Al(mal)3 group (The changes were 161.41%±42.13%, 101.16%±30.63%, 127.02%±29.58%, and 109.73%±15.61%, respectively, P < 0.05). Compared with the mNG group (1.00), the neuronal PTEN mRNA relative expression (0.67±0.11) and the PTEN protein expression (0.75±0.08) were decreased in the miR-29a group (P < 0.05); the PTEN mRNA relative expression (1.32±0.12) and the PTEN protein relative expression (1.46±0.15) in the mNG+20 μmol·L−1 Al(mal)3 group were increased (P < 0.05). Compared with the mNG+20 μmol·L−1 Al(mal)3 group, the PTEN mRNA relative expression (0.93±0.06) and the PTEN protein relative expression (0.92±0.09) were decreased in the miR-29a+20 μmol·L−1 Al(mal)3 group (P < 0.05). Conclusion Aluminum significantly inhibits the electrical activity of hippocampal neuronal networks, and miRNA-29a may be involved in the aluminum-induced impairment of hippocampal neuronal network electrical activity by regulating PTEN expression.

Shenbai Jiedu Prescription Inhibits Proliferation of Colorectal Cancer Cells by Regulating PTEN/PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the mechanism of Shenbai Jiedu prescription inhibiting the proliferation of HCT116 colorectal cancer （CRC） cells by regulating the phosphatase and tensin homolog deleted on chromosome ten （PTEN）/phosphatidylinositol 3-kinase （PI3K）/ protein kinase B （Akt） signaling pathway. MethodShenbai Jiedu prescription was extracted by water extraction and alcohol precipitation to prepare freeze-dried powder. HCT116 cells were cultured in vitro， and treated with different concentrations of Shenbai Jiedu prescription （2， 4， 8， 16 g·L-1）. The inhibitory effect of Shenbai Jiedu prescription on the proliferation of HCT116 cells was tested by methyl thiazolyl tetrazolium （MTT）. Real-time quantitative PCR was used to detect the mRNA expression levels of PTEN， PI3K， Akt， glycogen synthase kinase-3β （GSK-3β）， c-Myc， survivin and Cyclin D1. Western blot was employed to measure the protein expression levels of PTEN， phosphorylated PTEN （p-PTEN）， PI3K， Akt， phosphorylated Akt （p-Akt）， GSK-3β， phosphorylated GSK-3β （p-GSK-3β）， c-Myc， survivin and Cyclin D1， β-catenin nuclear import was explored by immunofluorescence assay. ResultCompared with the control group， Shenbai Jiedu prescription inhibited the proliferation of HCT116 cells in a dose-dependent manner （P<0.01）. Compared with the control group， the mRNA expression levels of PTEN and GSK-3β were up-regulated whereas those of PI3K， Akt， c-Myc， survivin and CyclinD1 were down-regulated after treatment with Shenbai Jiedu prescription （P<0.01）. The protein expression levels of PTEN， p-PTEN and GSK-3β were up-regulated whereas those of PI3K， Akt， p-Akt， GSK-3β， p-GSK-3β， c-Myc， survivin and CyclinD1 were down-regulated （P<0.05， P<0.01）. Immunofluorescence assay showed that Shenbai Jiedu prescription suppressed β-catenin nuclear import in HCT116 cells. ConclusionShenbai Jiedu prescription inhibited the proliferation of HCT116 cells via the mechanism of regulating the PTEN/PI3K/Akt signaling pathway.

The overall action molecular mechanism of anti-hepatitis B active extracts in Flos chrysanthemi indici based on epigenetics and metabonomics / 药学学报

Using the concepts and methods of epigenetics and metabolomics, to investigate the overall action molecular mechanism of Chrysanthemi indici C (CIC), the anti-hepatitis B virus (HBV) active extracts from Flos chrysanthemi indici. The inhibitory effects of CIC on proliferation and hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg) and HBV-DNA of HepG2.2.15 cells were detected by CCK-8 and antigen kit. The DNA methyltransferases (DNMTs)/ten-eleven-translocation-2 (TET2) equilibrium was detected by ELISA. Illumina 850K methylation chip, pyrosequencing and qPCR were used to determine the action pathway and target of CIC by GO and KEGG analysis. Cell metabolites were extracted with 80% methanol, and the changes of differential metabolites, differential metabolic pathways and cell microenvironment were detected by LC-MS and other metabolomics methods. The results showed that CIC could inhibit the proliferation, HBsAg, HBeAg and HBV-DNA of HepG2.2.15 cells obviously, down-regulate DNA methyltransferase 1 (DNMT1), DNA methyltransferase 3a (DNMT3a) and DNA methyltransferase 3b (DNMT3b), up-regulate TET2, and restore the balance of DNMTs/TET2. The action targets of CIC were phospholipase C gamma 2 (PLCG2), phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2), 5-hydroxytryptamine receptor 2B (HTR2B), nerve growth factor (NGF), mainly involved in lipid metabolism, inflammation mediated regulation of transient receptor potential (TRP), phospholipase D signaling and advanced glycation end product-receptor for AGE (AGE-RAGE) signaling in diabetic complications pathways. CIC could significantly affect fatty acid metabolism and had great influence on phenolic acid, alkaloid and lipid metabolites in cell microenvironment. These results suggest that the action mechanism of CIC may be the synergistic action of multiple pathways and multiple targets, including related inflammatory pathways, immune pathways and lipid metabolism, through regulating epigenetic expression balance and restoring the balance of cell microenvironment.

Targeting GATA1 and p2x7r Locus Binding in Spinal Astrocytes Suppresses Chronic Visceral Pain by Promoting DNA Demethylation / 神经科学通报·英文版

Irritable bowel syndrome is a gastrointestinal disorder of unknown etiology characterized by widespread, chronic abdominal pain associated with altered bowel movements. Increasing amounts of evidence indicate that injury and inflammation during the neonatal period have long-term effects on tissue structure and function in the adult that may predispose to gastrointestinal diseases. In this study we aimed to investigate how the epigenetic regulation of DNA demethylation of the p2x7r locus guided by the transcription factor GATA binding protein 1 (GATA1) in spinal astrocytes affects chronic visceral pain in adult rats with neonatal colonic inflammation (NCI). The spinal GATA1 targeting to DNA demethylation of p2x7r locus in these rats was assessed by assessing GATA1 function with luciferase assay, chromatin immunoprecipitation, patch clamp, and interference in vitro and in vivo. In addition, a decoy oligodeoxynucleotide was designed and applied to determine the influence of GATA1 on the DNA methylation of a p2x7r CpG island. We showed that NCI caused the induction of GATA1, Ten-eleven translocation 3 (TET3), and purinergic receptors (P2X7Rs) in astrocytes of the spinal dorsal horn, and demonstrated that inhibiting these molecules markedly increased the pain threshold, inhibited the activation of astrocytes, and decreased the spinal sEPSC frequency. NCI also markedly demethylated the p2x7r locus in a manner dependent on the enhancement of both a GATA1-TET3 physical interaction and GATA1 binding at the p2x7r promoter. Importantly, we showed that demethylation of the p2x7r locus (and the attendant increase in P2X7R expression) was reversed upon knockdown of GATA1 or TET3 expression, and demonstrated that a decoy oligodeoxynucleotide that selectively blocked the GATA1 binding site increased the methylation of a CpG island in the p2x7r promoter. These results demonstrate that chronic visceral pain is mediated synergistically by GATA1 and TET3 via a DNA-demethylation mechanism that controls p2x7r transcription in spinal dorsal horn astrocytes, and provide a potential therapeutic strategy by targeting GATA1 and p2x7r locus binding.

Analysis of the trend of medication use in patients with ulcerative colitis in a single center from 2010 to 2019 / 中华消化杂志

Objective:To analyze the trend of medication use in patients with ulcerative colitis (UC) in recent ten years in at Xijing Hospital, Air Force Military Medical University.Methods:From 2010 to 2019, the clinical data of 1 425 patients diagnosed with UC in the Department of Gastroenterology at Xijing Hospital, Air Force Medical University, were retrospectively collected. According to the period of medication, the UC patients were divided into year 2010 to 2014 group and year 2015 to 2019 group. The general information and the medication trend of year 2010 to 2014 group and year 2015 to 2019 group were analyzed. And then according to gender and age (<40 years old and ≥40 years old), patients were divided into subgroups and analyzed. Independent sample t test and chi-square test were used for statistical analysis. Results:The number of UC patients of year 2010 to 2014 group and year 2015 to 2019 group was 369 and 1 056, respectively. The percentages of patients in remission of the two groups were 9.5% (35/369) and 12.0% (127/1 056), respectively; the percentages of mild patients were 40.4% (149/369) and 41.6% (439/1 056), respectively; the percentages of moderate patients were 37.4% (138/369) and 28.9% (305/1 056), respectively; the percentages of severe patients were 12.7% (47/369) and 17.5% (185/1 056), respectively. There was no significant difference in the proportion of UC patients with different degrees between year 2010 to 2014 group and year 2015 to 2019 group ( P>0.05). There were no significant differences in the age and proportion of female between the year 2010 to 2014 group and year 2015 to 2019 group ((46.2±15.3) years old vs. (44.6±30.6) years old; 45.8%, 169/369 vs. 44.8%, 473/1 056; both P>0.05). The utilization rates of 5-aminosalicylic acid (5-ASA), glucocorticoid, immunosuppressants, and biological agents of the year 2015 to 2019 group were all higher than those of the year 2010 to 2014 group (96.8%, 1 022/1 056 vs. 90.0%, 332/369; 29.9%, 316/1 056 vs. 14.6%, 54/369; 8.4%, 89/1 056 vs. 2.4%, 9/369; 4.8%, 51/1 056 vs. 0.5%, 2/369, respectively), and the differences were all statistically significant ( χ2=26.766, 33.256, 15.315 and 14.038, all P<0.01). Within each of the year 2010 to 2014 group and the year 2015 to 2019 group, there were no significant differences between the female and male in the age, utilization rates of 5-ASA, glucocorticoid, immunosuppressants and biological agents ((47.2±13.6) years old vs. (45.3±16.5) years old, (43.1±12.9) years old vs. (45.8±39.5) years old, 88.8%, 150/169 vs. 91.0%, 182/200; 96.8%, 458/473 vs. 96.7%, 564/583; 13.6%, 23/169 vs. 15.5%, 31/200; 28.3%, 134/473 vs. 31.2%, 182/583; 2.4%, 4/169 vs. 2.5%, 5/200; 7.0%, 33/473 vs. 9.6%, 56/583; 0 vs. 1.0%, 2/200; 5.3%, 25/473 vs. 4.5%, 26/583; all P>0.05). In the patients aged≥40 years old of the year 2010 to 2014 group, the proportion of females was higher than that of the patients aged <40 years old (50.2%, 121/241 vs. 37.5%, 48/128), and the utilization rate of 5-ASA in patients aged ≥40 years old was lower than that of patients aged <40 years old (85.9%, 207/241 vs. 97.7%, 125/128), and the differences were statistically significant ( χ2=5.438 and 12.824, P=0.020 and P<0.01). In the year 2010 to 2014 group, there were no statistically significant differences in the utilization rates of glucocorticoid, immunosuppressants and biological agents between patients aged ≥40 years old and patients aged <40 years old (13.7%, 33/241 vs. 16.4%, 21/128; 2.1%, 5/241 vs. 3.1%, 4/128; 0 vs. 1.6%, 2/128; all P>0.05). In the year 2015 to 2019 group, the utilization rate of biological agents in patients aged≥40 years old was lower than that in patients aged<40 years old (3.7%, 23/630 vs. 46.5%, 198/426), and the difference was statistically significant ( χ2=4.721, P=0.030). In the year 2015 to 2019 group, there were no statistically significant differences in female proportion, utilization rates of 5-ASA, glucocorticoid, immunosuppressants and biological agents between patients aged≥40 years old and patients aged <40 years old (43.7%, 275/630 vs. 46.5%, 198/426; 96.0%, 605/630 vs. 97.9%, 417/426; 29.7%, 187/630 vs. 30.3%, 129/426; 8.6%, 54/630 vs. 8.2%, 35/426; all P>0.05). Conclusions:Compared with year 2010 to 2014, the number of UC patients remarkably increased in the year 2015 to 2019 in the Department of Gastroenterology, Xijing Hospiatal, Air Force Medical University. The utilization rates of 5-ASA, glucocorticoid, immunosuppressants and biological agents all increased in UC patients. The medication trends of UC patients with different gender were almost the same. The medication trends of UC patients with different age were different.

Role of miR-23a/PTEN axis in the occurrence and development of colorectal cancer / 中华内分泌外科杂志

Objective:To analyze the expression of microRNA-23a (miR-23a) and phosphatase and tensin homolog detected on chromosome ten (PTEN) regulatory axis in LS513 cells, and to explore the effects of miR-23a and PTEN on the occurrence and development of CRC.Methods:LS513 cells were divided into blank control group (NG group) : cells were not specially treated, negative control group (NC group) : 5 μl Lipofectamine3000 and 50 pmol/μl NC were added, Inhibition of miR-23a expression group (miR-23a-inhibitor group) : miR-23a-inhibitor sequence was transfected. The mRNA levels of miR-23a and PTEN in LS513 cells were detected by real-time fluorescence quantitative PCR (qRT-PCR) ; the proliferation of LS513 cells was detected by MTT method; Transwell assay was used to detect cell migration and invasion; Western blotting was used to detect proliferation, migration, invasion and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway related proteins.Results:Compared with those in NG group and NC group, the level of miR-23a in miR-23a inhibitor group was significantly lower ( P<0.05) , and the expression levels of PTEN mRNA and protein were significantly higher ( P<0.05) . The results of MTT showed that, compared with those in NG group and NC group, the proliferation inhibition rate in miR-23a-inhibitor groupwas significantly higher ( P<0.05) , and the expression of PCNA protein was significantly lower ( P<0.05) . Compared with those in NG group and NC group, the migration number and invasion number of LS513 cells in miR-23a-inhibitor group were significantly lower ( P<0.05) , and the expression of MMP-9 and E-cadherin protein was significantly lower ( P<0.05) . Compared with those in NG group and NC group, the expression of p-pi3k/PI3K and p-atk/ATK protein in miR-23a-inhibitor group was significantly lower ( P<0.05) . Conclusion:Inhibition of miR-23a expression may up-regulate PTEN gene expression, inhibit PI3K/Akt pathway activation, and then inhibit the proliferation, migration and invasion of LS513 cells.

Improvement in dyspepsia related symptoms treated with acupuncture in 278 patients with postprandial distress syndrome: a secondary analysis of a multi-center randomized controlled trial / 中国针灸

OBJECTIVE@#To evaluate the clinical effect of acupuncture for the improvements in various dyspeptic symptoms of postprandial distress syndrome.@*METHODS@#The secondary analysis on the data of a multi-center randomized controlled trial (RCT) was conducted. 278 patients with postprandial distress syndrome were randomized into an acupuncture group (138 cases) and a sham-acupuncture group (140 cases). In the acupuncture group, acupuncture was applied to Baihui (GV 20), Danzhong (CV 17), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), Zusanli (ST 36), etc. In the sham-acupuncture group, 6 sites, neither located on meridians nor belonged to meridian acupoints, were selected and punctured shallowly. The duration of treatment was 20 min each time, 3 times a week, for 4 weeks totally in the two groups. The follow-up visit lasted for 12 weeks. The scores of dyspeptic symptoms were compared between the two groups before treatment, during treatment (in week 1, 2, 3 and 4) and during follow-up (in week 8, 12 and 16) separately.@*RESULTS@#Besides the scores of early satiety and vomiting in the sham-acupuncture group in week 1, the scores of the other dyspepsia symptoms during treatment and follow-up were all reduced in the two groups as compared with those before treatment (@*CONCLUSION@#Acupuncture remarkably relieves postprandial fullness, early satiety, upper abdominal bloating and belching in patients with postprandial distress syndrome.

Roles of ten eleven translocation proteins family and 5-hydroxymethylcytosine in epigenetic regulation of stem cells and regenerative medicine / 北京大学学报(医学版)

The methylation of cytosine is one of the most fundamental epigenetic modifications in mammalian genomes, and is involved in multiple crucial processes including gene expression, cell differentiation, embryo development and oncogenesis. In the past, DNA methylation was thought to be an irreversible process, which could only be diluted passively through DNA replication. It is now becoming increa-singly obvious that DNA demethylation can be an active process and plays a crucial role in biological processes. Ten eleven translocation (TET) proteins are the key factors modulating DNA demethylation. This family contains three members: TET1, TET2 and TET3. Although three TET proteins have relatively conserved catalytic domains, their roles in organisms are not repeated, and their expression has significant cell/organ specificity. TET1 is mainly expressed in embryonic stem cells, TET2 is mainly expressed in hematopoietic system, and TET3 is widely expressed in cerebellum, cortex and hippocampus. This family catalyzes 5-methylcytosine to 5-hydroxymethylcytosine and other oxidative products, reactivates silenced-gene expression, in turn maintains stem cell pluripotency and regulates lineage specification. With the development of tissue engineering, organ transplantation, autologous tissue transplantation and artificial prosthesis have been widely used in clinical treatment, but these technologies have limitations. Regenerative medicine, which uses stem cells and stem cell related factors for treatment, may provide alternative therapeutic strategies for multiple diseases. Among all kinds of human stem cells, adipose-derived stem cells (ADSCs) are the most prospective stem cell lineage since they have no ethical issues and can be easily obtained with large quantities. To date, ADSCs have been shown to have strong proli-feration capacity, secrete numerous soluble factors and have multipotent differentiation ability. However, the underlying mechanism of the proliferation, secretion, acquired pluripotency, and lineage specific differentiation of ADSCs are still largely unknown. Some studies have explored the role of epigenetic regulation and TET protein in embryonic stem cells, but little is known about its role in ADSCs. By studying the roles of TET proteins and 5-hydroxymethylcytosine in ADSCs, we could provide new theoretical foundation for the clinical application of ADSCs and the stem cell-based therapy. In the future, combined with bioprinting technology, ADSCs may be used in tissue and organ regeneration, plastic surgery reconstruction and other broader fields.

Cuidados de Enfermagem a um Adolescente com Necrólise Epidérmica Tóxica: Relato de Caso / Nursing Care of an Adolescent with Toxic Epidermal Necrolysis: A Case / Report Cuidados de enfermería prestados a un adolescente con necrólisis epidérmica tóxica: reporte de caso

Objetivo: Relatar a assistência de enfermagem diante do caso de um adolescente com diagnóstico de Necrólise Epidérmica Tóxica (NET) internado em uma Unidade de Terapia Intensiva de Queimados. Método: Trata-se de um relato de caso sobre as intervenções de enfermagem realizadas em um adolescente com diagnóstico de NET, internado por um mês em 2020 na Unidade de Terapia Intensiva de Queimados de Goiás. As informações foram coletadas do prontuário do paciente. Resultados: Apresentamos práticas clínicas para auxiliar no manejo de pacientes com NET. O caso apresentado teve um desfecho positivo. Conclusão: Os cuidados de enfermagem são essenciais para o prognóstico positivo do paciente. Nesse caso, a enfermagem atuava principalmente no cuidado de feridas, administração de medicamentos, laserterapia e vigilância para prevenção de infecções

Objective: To report nursing care facing a case of an adolescent diagnosed with Toxic Epidermal Necrolysis (TEN) hospitalized in a Burns Intensive Care Unit. Method: This is a case report on the nursing interventions performed on a teenager diagnosed with TEN, who was hospitalized for a month in 2020 at the Burn Intensive Care Unit in the state of Goiás. The information was collected from the patient's medical record. Results: We present clinical practices to assist the management of patients with TEN. The case presented had a positive outcome. Conclusion: Nursing care is essential for the positive prognosis of the patient. In this case, nursing acted mainly in wound care, medication administration, laser therapy and surveillance to prevent infections

Objetivo: Informar los cuidados de enfermería en el caso de un adolescente diagnosticado de Necrólisis Epidérmica Tóxica (TNE) ingresado en una Unidad de Cuidados Intensivos por Quemados. Método: Se trata de un relato de caso sobre las intervenciones de enfermería prestadas a un adolescente diagnosticado de TNE, hospitalizado durante un mes en 2020 en la Unidad de Cuidados Intensivos Quemados de Goiás, información obtenida de la história clínica del paciente. Resultados: Presentamos prácticas clínicas para ayudar en el manejo de pacientes con TNE. El caso presentado tuvo un resultado positivo. Conclusión: El cuidado de enfermería es fundamental para el pronóstico positivo del paciente. En este caso, la enfermería trabajó principalmente en el cuidado de heridas, administración de medicamentos, terapia con láser y vigilancia para prevenir infecciones.

Classification of caesarean section based on Robson ten group classification system in our hospital

Background: Recent data indicate that one in five women undergo caesarean section (CS). In the last decade, there has been a dramatic increase in the caesarean section rate worldwide, which now exceeds 30% in some regions. Thus, the increasing rate of caesarean section became a matter of international public health concern. Our study aimed to classify the CS-based on Robson ten group classification system (RTGCS) criteria which will subsequently enable us to standardise the indication of CS and establish protocols to reduce the number of CS in our set up.Method: A retrospective study was conducted in ESI Hospital, New Delhi wherein Robson TGCS was used to classify CS for 15 months (January 2019 to April 2020).Results: Overall CS rate in our hospital over the specified period was 34.5%. All women with one or more previous cesareans (group V) had the maximum number of cesareans, 37%, followed by nulliparous, single, cephalic, term pregnancy (induced) i.e group II, 22.1% and nulliparous women more than 37 weeks in spontaneous labour (group I), 9.5%.Conclusions: RTGCS is easy to comprehend and reproduce. All deliveries and cesareans should be universally categorized by the Robsons TGCS. An attempt should be made to evaluate the group contributing most to the CS rate and interventions should be made accordingly.

Inhibitory effect of celecoxib on Cal-27 tongue squamous cell carcinoma cell proliferation / 口腔疾病防治

Objective@# To explore the inhibitory effect of celecoxib (CELE) on the proliferation of tongue squamous cell carcinoma Cal-27 cells and its mechanism.@*Methods@# A CCK-8 assay was used to investigate the cytotoxicity of different concentrations CELE(10, 20, 40, 60, 80, and 100 mol/L) at 24 and 48 h in Cal-27 cells. According to the concentration of CELE, samples were divided into a control group (0 μmol/L) and experimental groups (10, 20, and 40 μmol/L), and cell invasiveness was detected by the Transwell method. The expression levels of c-Myc and Cyclin D1 mRNA were detected with qPCR, and western blots were used to detect the expression of phosphate and tension homologue deleted on chromosome ten (PTEN), phospho-protein kinase B (p-AKT) (Thr308), c-Myc, cyclin D1 and other proteins in Cal-27 cells after 24 h of treatment with different doses of CELE (10, 20, and 40 μ mol/L) and after 6, 12, and 24 h of treatment with 40 μmol/L CELE.@*Results @# The different concentrations of CELE were able to inhibit the proliferation of Cal-27 cells, and the higher the concentration of CELE was, the more significant the inhibition of the proliferation of Cal-27 cells was. The cell survival rates of cells exposed to 40 μmol/L CELE were 80% and 75% after 24 and 48 h, respectively. In the four groups of patients, the number of invasive cells was compared, and the results in decreasing order were the control group, 10 μmol/L CELE, 20 μmol/L CELE, and 40 μmol/L CELE. The expression level of c-Myc, cyclin D1 mRNA and the protein in P-AKT (Thr308), c-Myc, and cyclin D1 significantly decreased and the expression of PTEN protein increased in the Cal-27 cells after administration of CELE at different concentrations. @*Conclusion@# CELE can inhibit the proliferation of Cal-27 cells, possibly through inhibition of the expression of proliferation signal factors, such as c-Myc and cyclin D1, by activating the PTEN signaling pathway.

Clinical observation of "experienced ten acupoints" for functional dyspepsia of liver stagnation and spleen deficiency / 中国针灸

OBJECTIVE@#To verify the clinical effect of acupuncture at "experienced ten acupoints" for functional dyspepsia (FD) of liver stagnation and spleen deficiency.@*METHODS@#A total of 96 patients with FD of liver stagnation and spleen deficiency were randomly divided into an observation group and a control group, 48 cases in each group. In the observation group, "experienced ten acupoint" prescription was applied，acupoints included Shangwan (CV 13), Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6), Tianshu (ST 25), Zusanli (ST 36) and Neiguan (PC 6). In the control group, irrelevant acupoint prescription was applied, acupoints included Feiyang (BL 58), Heding (EX@*RESULTS@#Compared before treatment, the symptom score after treatment was decreased in the observation group (@*CONCLUSION@#Acupuncture at "experienced ten acupoints" can improve symptoms in patients with FD of liver stagnation and spleen deficiency, has the better clinical effect.

Robson ten groups classification system for caesarean section audit: are our operation theatre registers RTGC enabled?

Background: Rising caesarean section rate is a global problem. Robson ten groups classification (RTGC) system of audit has been recommended as the first step towards planning strategies to reduce caesarean section rate. Getting data for this audit is often difficult. If operation theatre (OT) registers are maintained properly this would become easy. The study proposes to know if enough information is available in the operation theatre registers to get caesarean section data for ten groups of Robson classification system. To suggest changes in OT register format for future convenience.Methods: We studied data from 100 consecutive caesarean section entries in OT registers from two medical college institutions to know if the information recorded is adequate to classify these 100 caesarean sections into ten groups given by Robson. Last 100 caesarean section entries into the OT register during the period 1st April 2018 till 31st March 2019 were studied.Results: Presentation of the foetus was the only factor which could be clearly known for all 100 cases. Labour onset whether spontaneous or induced was the least recorded observation in traditional operation theatre registers. The next information which was commonly not recorded was the labour status (woman in labour or not in labour) at the time of caesarean section.Conclusions: For Robson’s classification of caesarean sections to become useful tool to guide strategies in reducing caesarean sections we need to modify format of our OT registers. Traditional OT registers do not provide enough information to categorize caesarean section cases into Robson ten groups. Missing information makes caesarean section audit imperfect or impossible. We suggest a format for it to be incorporated into the operation theatre registers of centres providing maternity services.

A study of cesarean section rate by using modified Robson's ten group classification system

Background: High caesarean section rate worldwide including India is matter of concern. The Robson’s Ten-group classification system allows critical analysis of caesarean deliveries according to characteristics of pregnancy. The objective was to analyze caesarean section rates in a tertiary care centre according to Modified Robson’s ten groups classification.Methods: This retrospective study was conducted at GMERS Gotri Medical College, Vadodara, Gujarat, India. All patients who delivered between August 2018 and March 2019, were included in the study. Women were classified in 10 groups according to modified Robson’s classification using their maternal characteristics and obstetric history. For each group, authors calculated the caesarean section rate within the group and its absolute and relative contribution to the overall caesarean rate.Results: Total number of delivery in my study institute in 8 months was 1531 out of them 456 was cesarean section, so the overall caesarean section rate was 29.78%. The main contributions to overall caesarean rate was 40.78% by group 5 (previous CS, singleton, cephalic, >37weeks) followed by 14.25% by group 1 (nullipara, singleton, cephalic, >37 weeks, spontaneous labour), 11.40% by group 2 (nullipara, singleton, cephalic,>37 weeks, induced or CS before labour). CS rates among various group ranges from 100% among women with abnormal lie (group 9) to 98.4% in previous CS (group 5), 84% in nulliparous breech (group 6), 58% in multiparous breech (group 7) and least 8.2% in multipara spontaneous labour (group 3).Conclusions: The Robson’s classification is easy to use. It is time to implement obstetric audit to lower the overall CS rates.