Exploration of molecular mechanism of Selaginella moelledorffii Hieron. in treatment of laryngeal cancer based on network-based pharmacology, molecular docking techniques and experimental validation / 中国药理学通报

Aim To explore the molecular mechanism of Selaginella moelledorffii Hieron. in the treatment of laryngeal cancer. Methods According to the relevant literature reports, the chemical constituents of S. moellendorffii were obtained, and the active ingredients were screened out through the SwissADME database, and the targets were screened through the PharmMapper database. The laryngeal cancer-related targets were collected by searching OMIM and other databases, and the Venny 2.1.0 online platform was used to obtain the intersection of the two. Protein interaction analysis of the potential targets was performed using the STRNG platform. GO functional analysis and KEGG pathway analysis was carried out using DAVID database. Visual networks were built with Cytoscape 3.8.0 software. Molecular docking was validated by SYBYL-X 2. 0 software. MTT method, Hoechst 33258 staining method and Western blotting were also used for validation. Results At the molecular level, a total of 110 active ingredients of S. moellendorffii and 82 drug targets were screened out, 1,608 targets related to laryngeal cancer, and intersection of 34 targets. GO analysis yielded 135 entries, and KEGG analysis yielded a total of 61 pathways. Molecular docking results showed that the 11 key active ingredients such as 2", 3"-dihydrooch-naflavone wood flavonoids and 4 core target proteins such as MAPK1 had 95. 5% of good docking activity. At the cellular level, SM-BFRE was screened for its strongest inhibitory effect on laryngeal cancer cell proliferation through MTT assay. Furthermore, Hoechst 33258 staining showed that the decrease in Hep-2 cell viability produced by SM-BFRE was related to cell apoptosis. Finally, Western blot verified that SM-BFRE inhibited PI3K/Akt/NF through inhibition- K B/COX-2 pathway to induce apoptosis in laryngeal cancer cells. Conclusions To sum up, it fully reflects the multicomponent, multi-target, and multi-channel synergistic effect of S. moellendorffii in the treatment of laryngeal cancer, and provides a theoretical reference for further elucidation of the mechanism of action of S. moellendorffii in the treatment of laryngeal cancer.

Mechanism and experimental validation of Zukamu granules in treatment of bronchial asthma based on network pharmacology and molecular docking / 中国药理学通报

Aim To anticipate the mechanism of zuka- mu granules (ZKMG) in the treatment of bronchial asthma, and to confirm the projected outcomes through in vivo tests via using network pharmacology and molecular docking technology. Methods The database was examined for ZKMG targets, active substances, and prospective targets for bronchial asthma. The protein protein interaction network diagram (PPI) and the medication component target network were created using ZKMG and the intersection targets of bronchial asthma. The Kyoto Encyclopedia of Genes and Genomics (KEGG) and gene ontology (GO) were used for enrichment analysis, and network pharmacology findings were used for molecular docking, ovalbumin (OVA) intraperitoneal injection was used to create a bronchial asthma model, and in vivo tests were used to confirm how ZKMG affected bronchial asthma. Results There were 176 key targets for ZKMG's treatment of bronchial asthma, most of which involved biological processes like signal transduction, negative regulation of apoptotic processes, and angiogenesis. ZKMG contained 194 potentially active components, including quercetin, kaempferol, luteolin, and other important components. Via signaling pathways such TNF, vascular endothelial growth factor A (VEGFA), cancer pathway, and MAPK, they had therapeutic effects on bronchial asthma. Conclusion Key components had strong binding activity with appropriate targets, according to molecular docking data. In vivo tests showed that ZKMG could reduce p-p38, p-ERKl/2, and p-I

Mechanism of Qizhenziyin mixture in the treatment of hypogonadism based on network pharmacology analysis and molecular docking / 药学实践杂志

Objective To investigate the mechanism of Qizhenziyin mixture in the treatment of hypogonadism by using the network pharmacology approach. Methods The active components of Qizhenziyin mixture were obtained by searching TCMSP ，TCMID and HIT databases.The related targets of candidate compounds were obtained by searching STITCH databases. The potential targets of Qizhenziyin mixture in the treatment of hypogonadism were obtained by mapping the disease genes of hypogonadism with Genecards and DisGeNet databases. The protein interaction platform database (STRING) was used to construct the interaction relationship between action targets. The target protein interaction （PPI） network was constructed by introducing Cytoscape software. The mechanism of Qizhenziyin mixture in the treatment of hypogonadism was explained through the enrichment analysis of GO, KEGG and molecular docking technology. Results A total of 148 drug-disease chemical compounds, 96 drug-disease intersection targets, 1085 disease targets were obtained；the components for treating diseases are: quercetin，kaempferol, luteolin, etc; enrichment analysis of GO revealed 1792 biological processes （BP）, 31 cellular components (CC) and 79 molecular functions (MF)；the results of KEGG pathway enrichment analysis indicated such as FOXO signaling pathway, prostate cancer, AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, etc.The results of molecular docking showed that kaempferol and LEP had the best and stable binding energy. Conclusion The active components of Qizhenziyin mixture may play a role of the treatment of hypogonadism by improving insulin resistance and the expression of testosterone synthetase of Leydig cells.

Mannitol inhibits the proliferation of neural stem cell by a p38 mitogen-activated protein kinase-dependent signaling pathway / 中华创伤杂志(英文版)

PURPOSE@#Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.@*METHODS@#C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference.@*RESULTS@#Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.@*CONCLUSIONS@#Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Clinical research progress of palbociclib in treatment of breast cancer / 中国临床药理学与治疗学

Palbocicril, the first cyclin-dependent kinases 4 and 6 inhibitors, is a crucial milestone in the development history of antineoplastic drugs. It combined with aromatase inhibitor or fulvestrant as first-line, second-line or post-line therapy has good efficacy and safety for hormone receptor-positive, human epidermal growth factor receptor-2 negative locally advanced or metastatic breast cancer, which has a good application prospect. This article summarizes the clinical trials and safety studies related to palbociclib.

Analysis of the maternal and fetal adverse outcomes of 154 pregnant women with cesarean section in the second stage of labor / 中华妇产科杂志

Objective: To investigate the perinatal maternal and fetal adverse outcomes of cesarean section in the different duration of the second stage of labor. Methods: A retrospective cohort study was conducted on the clinical data of 154 pregnant women with singleton head pregnancy who underwent cesarean section at different times of the second stage of labor due to maternal and fetal factors in the First Affiliated Hospital of Nanjing Medical University from January 1, 2019 to December 31, 2021. According to the duration of the second stage of labor, they were divided into <2 h group (54 cases), 2-<3 h group (61 cases), and ≥3 h group (39 cases). The general data of pregnant women and neonates, preoperative maternal and neonatal conditions related to labor stages, surgical indications, surgical procedures, and perioperative maternal and neonatal adverse outcomes were compared among the three groups. Results: (1) General Information: there were no significant differences in maternal age, gravidity and parity, proportion of primipara, gestational age at delivery, body mass index before delivery, pregnancy complications, labor analgesia rate and the duration of the first stage of labor among the three groups (all P>0.05). The differences of the gender composition, birth weight and incidence of macrosomia of the three groups were also not statistically significant (all P>0.05). (2) Maternal and fetal status and surgical indications: the incidence of intrapartum fever and type Ⅱ and Ⅲ fetal heart rate monitoring in the <2 h group were higher than those in the 2-<3 h group and the ≥3 h group, and the preoperative fetal head position in the ≥3 h group was lower than that in the 2-<3 h group, with statistically significant differences (all P<0.05). The proportion of cesarean section due to "fetal distress" was 40.7% (22/54) in the <2 h group, which was higher than that in the 2-<3 h group (4.9%, 3/61) and the ≥3 h group (2.6%, 1/39). The proportions of surgical indication of "relative cephalo-pelvic disproportion" were 98.4% (60/61) and 94.9% (37/39) in the 2-<3 h group and ≥3 h group, respectively, and the surgical indication of "fetal head descent arrest" were 41.0% (25/61) and 59.0% (23/39), respectively. Compared with <2 h group [63.0% (34/54), 13.0% (7/54)], the differences were statistically significant (all P<0.05). There were no significant difference in surgical indications between 2-<3 h group and ≥3 h group (all P>0.05). (3) Intraoperative conditions and perioperative complications of cesarean section: the puerperal morbidity rate of <2 h group was 37.0% (20/54), which was higher than those of 2-<3 h group (18.0%, 11/61) and ≥3 h group (7.7%, 3/39), the difference was statistically significant (P<0.05). There were no significant differences in operation time, intraoperative blood loss, incidence of fetal head inlay, uterine incision tear, modified B-Lynch suture for uterine atony, postpartum hemorrhage, perioperative blood transfusion, preoperative hemoglobin (Hb) level, perioperative Hb change, and postoperative hospital stay among the three groups (all P>0.05). (4) Adverse neonatal outcomes: non-hemolytic neonatal hyperbilirubinemia in ≥3 h group was 35.9% (14/39), which was significantly higher than that in <2 h group (13.0%, 7/54; P<0.05). Among the neonates admitted to neonatal intensive care unit (NICU) within 1 week after birth, the proportion of neonates admitted to NICU due to neonatal hyperbilirubinemia in ≥3 h group (15/19) was significantly higher than that in <2 h group (9/17) and 2-<3 h group (10/19), and the differences were statistically significant (all P<0.05). However, there was no significant difference between the <2 h group and the 2-<3 h group (P>0.05). There was no perinatal death in the three groups. Conclusions: The rate of puerperal morbidity is higher in patients who were transferred to cesarean section within 2 hours of the second stage of labor. In the early stage of the second stage of labor, the monitoring of fetal heart rate and amniotic fluid characteristics should be strengthened, especially the presence or absence of prenatal fever. In good maternal and neonatal conditions, conversion to cesarean section after 2 hours of the second stage of labor does not significantly increase the incidence of serious adverse maternal and neonatal outcomes. For the second stage of labor more than 3 hours before cesarean section, it is necessary to strengthen the monitoring of neonatal bilirubin.

Research advances in signaling pathways associated with potential anti-liver fibrosis drugs and targets / 临床肝胆病杂志

Liver fibrosis is a key step in the progression of chronic liver diseases to liver cirrhosis and even liver cancer. In recent years， a large number of studies have shown the necessity of intervening in the process of liver fibrosis， and various anti-liver fibrosis drugs and active ingredients have been discovered. Non-coding RNAs also play an important role in the process of liver fibrosis， and searching for upstream non-coding RNAs that can regulate signaling pathways can provide new insights for anti-liver fibrosis treatment. This article introduces the process of liver fibrosis mediated by the TGF-β， Wnt/β-catenin， PI3K/Akt/mTOR， NF-κβ， Hippo， and MAPK signaling pathways， lists the latest anti-liver fibrosis drugs or active components in each signaling pathway， and summarizes the research advances in anti-liver fibrosis targets and drugs mediated by related non-coding RNAs， so as to provide new research ideas and treatment methods for anti-liver fibrosis treatment.

Research Progress of Lung Cancer Vaccines / 中国肺癌杂志

With the development of medical technology, tumor vaccines as a novel precise immunotherapy approach have gradually received attention in clinical applications. Against the backdrop of the global corona virus disease 2019 (COVID-19) outbreak, vaccine technology has further advanced. Depending on the types of antigens, tumor vaccines can be divided into whole-cell vaccines, peptide vaccines, messenger ribonucleic acid (mRNA) vaccines, recombinant virus vaccines, etc. Although some tumor vaccines have been marketed and achieved certain therapeutic effects, the results of tumor vaccines in clinical trials have been unsatisfactory in the past period. With the maturation of next-generation sequencing (NGS) technology and the continuous development of bioinformatics, dynamic monitoring of the entire process of tumor subpopulation development has become a reality, which has laid a solid foundation for personalized, neoantigen-centered therapeutic tumor vaccines. This article reviews the recent developments of tumor vaccines of different types, starts with lung cancer and summarizes the achievements of tumor vaccines in clinical applications, and provides an outlook for the future development of antigen-centered tumor vaccines.
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Determination of camphor residue and borneol content in Qingchang suppository by GC / 药学实践杂志

Objective To establish a gas chromatography for simultaneous determination of camphor residue and borneolum content in Qingchang Suppository. Methods Gas chromatograph method was used. The chromatographic column was Agilent capillary column(30 m×0.25 mm×0.25 µm). The column temperature was 140 ℃. The sample injection temperature was 250 ℃. The FID detector temperature was 250 ℃. Results Camphor，borneol and isoborneol content showed good linear in the extent of 0.0299~1.497(r=1.000), 0.0205~1.025(r=1.000), 0.0097~0.4830 µg (r=1.000). RSDs of precision，stability and repeatability test results were less than 2%. The recovery was 99.7%, 101.0%, 102.5%. Conclusion This method is simple and quick with accurate result, which could be used for the content determination of Borneol in Qingchang Suppository.

Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice / 中西医结合学报

OBJECTIVE@#Recent investigations have demonstrated that Polygonum perfoliatum L. can protect against chemical liver injury, but the mechanism behind its efficacy is still unclear. Therefore, we studied the pharmacological mechanism at work in P. perfoliatum protection against chemical liver injury.@*METHODS@#To evaluate the activity of P. perfoliatum against chemical liver injury, levels of alanine transaminase, lactic dehydrogenase, aspartate transaminase, superoxide dismutase, glutathione peroxidase and malondialdehyde were measured, alongside histological assessments of the liver, heart and kidney tissue. A nontargeted lipidomics strategy based on ultra-performance liquid chromatography quadrupole-orbitrap high-resolution mass spectrometry method was used to obtain the lipid profiles of mice with chemical liver injury and following treatment with P. perfoliatum; these profiles were used to understand the possible mechanisms behind P. perfoliatum's protective activity.@*RESULTS@#Lipidomic studies indicated that P. perfoliatum protected against chemical liver injury, and the results were consistent between histological and physiological analyses. By comparing the profiles of liver lipids in model and control mice, we found that the levels of 89 lipids were significantly changed. In animals receiving P. perfoliatum treatment, the levels of 8 lipids were significantly improved, relative to the model animals. The results showed that P. perfoliatum extract could effectively reverse the chemical liver injury and significantly improve the abnormal liver lipid metabolism of mice with chemical liver injury, especially glycerophospholipid metabolism.@*CONCLUSION@#Regulation of enzyme activity related to the glycerophospholipid metabolism pathway may be involved in the mechanism of P. perfoliatum's protection against liver injury. Please cite this article as: Peng L, Chen HG, Zhou X. Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice. J Integr Med. 2023; 21(3): 289-301.

Spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.

Quality evaluation of Commelina communis from different origins based on multicomponent content determination combined with chemometrics / 中国中药杂志

This research established a high-performance liquid chromatography(HPLC) method for simultaneous determination of isoorientin, orientin, vitexin, and isovitexin in Commelina communis to conduct content difference analysis and quality evaluation of 62 batches of C. communis from different origins. The HPLC content determination was performed on a Dikma Platisil ODS chromatographic column(4.6 mm×250 mm, 5 μm), with acetonitrile-0.1% formic acid(14∶86) as the mobile phase. The detection wavelength was set at 348 nm, the flow rate was 1.0 mL·min~(-1), and the column temperature was 35 ℃. The differences in origins and quality of 62 batches of C. communis were studied by chemometrics. The results showed that the determination of four components mani-fested a good linear relationship in the range of mass concentration(r>0.999 9), and the average recovery rate was 96.17%-103.0%. The relative standard deviations(RSDs) of precision, stability, and repeatability were all less than 2.0%. The content of four components from high to low was isoorientin>isovitexin>orientin>vitexin. Forty-seven batches of C. communis with clear origins were classified into six categories by chemometrics. C. communis from different origins had different qualities. Generally, C. communis from Western China, Central China, and South of China had superior qualities. The HPLC method established in this study is specific, simple, and efficient, which provides references for the comprehensive evaluation of the quality of C. communis. The chemometrics shows that the qualities of C. communis from different origins are largely different. Isoorientin can be used as an index to determine the content of C. communis, and its content limit should be set no less than 0.023%.

Mechanism of Qiwei Guibao Granules in treatment of premature ovarian failure based on proteomics / 中国中药杂志

In this study, the underlying mechanism of Qiwei Guibao Granules(QWGB) in the treatment of premature ovarian fai-lure(POF) was explored by the proteomics technique. Firstly, the POF model was induced in mice by intragastric administration of Tripterygium wilfordii glycosides solution at 50 mg·kg~(-1) for 14 days. Ten days prior to the end of the modeling, the estrous cycle of mice was observed every day to evaluate the success of modeling. From the 1st day after modeling, the POF model mice were treated with QWGB by gavage every day and the treatment lasted four weeks. On the 2nd day after the end of the experiment, blood was collected from the eyeballs and the serum was separated by centrifugation. The ovaries and uterus were collected and the adipose tissues were carefully stripped. The organ indexes of the ovaries and uterus of each group were calculated. The serum estrogen(E_2) level of mice in each group was detected by ELISA. Protein samples were extracted from ovarian tissues of mice, and the differential proteins before and after QWGB intervention and before and after modeling were analyzed by quantitative proteomics using tandem mass tags(TMT). As revealed by the analysis of differential proteins, QWGB could regulate 26 differentially expressed proteins related to the POF model induced by T. wilfordii glycosides, including S100A4, STAR, adrenodoxin oxidoreductase, XAF1, and PBXIP1. GO enrichment results showed that the 26 differential proteins were mainly enriched in biological processes and cellular components. The results of KEGG enrichment showed that those differential proteins were involved in signaling pathways such as completion and coalescence cascades, focal adhesion, arginine biosynthesis, and terpenoid backbone biosynthesis. The complement and coalescence cascades signaling pathway was presumably the target pathway of QWGB in the treatment of POF. In this study, the proteomics technique was used to screen the differential proteins of QWGB in the treatment of POF in mice induced by T. wilfordii glycosides, and they were mainly involved in immune regulation, apoptosis regulation, complement and coagulation cascade reactions, cholesterol metabolism, and steroid hormone production, which may be the main mechanisms of QWGB in the treatment of POF.

Effects of different extraction methods on chemical compositions and biological activities of polysaccharides from Lycium barbarum / 中国中药杂志

In this study, five polysaccharides from Lycium barbarum(LBPs)(LBP-1-LBP-5) were selectively extracted by different extraction methods, and the chemical composition, structural characteristics, and biological activities of LBPs were explored. The results of chemical composition analysis showed that alkaloids were not detected in the five LBPs. The total polysaccharide content was(81.95%±1.6%)-(92.96%±0.76%), the uronic acid content was(8.26%±0.46%)-(24.81%±0.46%), and the protein content was(0.06%±0.03%)-(1.35%±0.13%). The monosaccharide compositions of the five LBPs were basically same, mainly including glucose, xylose, and galactose. However, there was significant difference in the content ratio of different monosaccharide. The results of infrared spectra analysis indicated that the five LBPs had typical infrared spectral characteristics of polysaccharides. The results of nuclear magnetic resonance characteristic spectrum analysis revealed that the five LBPs had two configurations of α and β. Meanwhile, there were triple helix structures in LBP-2, LBP-3, and LBP-4, which enhanced the activities of polysaccharides. The results of activities screening suggested that the biological activities of the five LBPs were significantly different. LBP-3 showed the highest lipid oxidation clearance rate, and its antioxidant activity was equivalent to that of the positive control group. The inhibitory rate of LBP-4 on α-amylase and its activation rate of alcohol dehydrogenase were better than those of other fractions, and the inhibitory rate of LBP-4 on α-amylase was slightly higher than that of the positive control group when the mass concentration was 10 g·L~(-1). LBP-2 showed stronger inhibitory activity against α-glucosidase and hyaluronidase. This study provides references for the precise development and utilization of LBPs.

Analysis of Long-Term Prognostic Factors Based on Nutritional Status in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To explore the prognostic factors of patients with multiple myeloma (MM) based on nutritional status.@*METHODS@#The Controlling Nutritional Status (CONUT) score and clinical parameters at diagnosis of 203 newly diagnosed MM patients hospitalized in the department of hematology, Wuxi People's Hospital from January 1, 2007 to June 30, 2019 were analyzed retrospectively. The best cut-off value was determined by ROC curve, and the patients were divided into high CONUT group (>6.5 points) and low CONUT group (≤6.5 points); through COX regression multivariate analysis of overall survival (OS) time, CONUT, ISS stage, LDH and treatment response were selected for multiparameter prognostic stratification.@*RESULTS@#The OS of MM patients in high CONUT group was shorter. The low-risk group (≤2 points) of the multiparameter risk stratification had longer OS time and progression-free survival (PFS) time compared with the high-risk group (>2 points), and it was also effective for different age or karyotype subgroups, new drug groups containing bortezomib and transplant-ineligible subgroup.@*CONCLUSION@#The risk stratification of MM patients based on CONUT, ISS stage, LDH and treatment response is worthy of clinical application.

Association between blood pressure during 12-28 weeks gestation and pre-eclampsia: predictive value of blood pressure trajectories constructed by latent class growth modeling / 中华心血管病杂志

Objective: To explore the associations between blood pressure trajectories during pregnancy and risk of future pre-eclampsia in a large cohort enrolling pregnant women at gestational age of ~12 weeks from community hospitals in Tianjin. Latent class growth modeling (LCGM) was used to model the blood pressure trajectories. Methods: This was a large prospective cohort study. The study enrolled pregnant women of ~12 weeks of gestation in 19 community hospitals in Tianjin from November 1, 2016 to May 30, 2018. We obtained related information during 5 antepartum examinations before gestational week 28, i.e., week 12, week 16, week 20, week 24 and week 28. LCGM was used to model longitudinal systolic (SBP) and diastolic blood pressure (DBP) trajectories. For the association study, the predictors were set as SBP and DBP trajectory membership (built separately), the outcome was defined as the occurrence of preeclampsia after 28 weeks of gestation. Results: A total of 5 809 cases with known pregnant outcomes were documented. After excluding 249 cases per exclusion criteria, 5 560 cases with singleton pregnancy were included for final analysis. There were 128 cases preeclampsia and 106 cases gestational hypertension in this cohort. Univariate logistic regression and multivariate logistic regression showed the higher baseline SBP level and DBP level were related with increased risk of preeclampsia. Four distinctive SBP trajectories and DBP trajectories from 12 weeks to 28 weeks of gestation were identified by LCGM. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for SBP latent classification trajectory_ 4 was 4.023 (95%CI: 2.368 to 6.835, P<0.001), and the OR for SBP latent classification trajectory_3 was 1.854 (95%CI: 1.223 to 2.811, P=0.004). Logistic regression showed that: using the DBP latent classification trajectory_1 as the reference group, the OR for DBP latent classification trajectory_4 was 4.100 (95%CI: 2.571 to 6.538, P<0.001), and 2.632 (95%CI: 1.570 to 4.414, P<0.001) for DBP latent classification trajectory_2. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for DBP_traj_4 was 2.527 (95%CI: 1.534 to 4.162, P<0.001), and the OR for DBP_traj_3 was 1.297 (95%CI: 0.790 to 2.128, P=0.303), and 2.238 (95%CI: 1.328 to 3.772, P=0.002) for DBP_traj_2. Therefore, BP trajectories from 12 weeks to 28 weeks identified by LCGM served as novel risk factors that independently associated with the occurrence of preeclampsia. Receiver operating characteristic (ROC) curve analysis showed incremental diagnostic performance by combing baseline blood pressure levels with blood pressure trajectories. Conclusion: By applying LCGM, we for the first time identified distinctive BP trajectories from gestational week 12 to 28, which can independently predict the development of preeclampsia after 28 weeks of gestation.

Analysis of clinicopathological and molecular abnormalities of angioimmunoblastic T-cell lymphoma / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinicopathological features, molecular changes and prognostic factors in angioimmunoblastic T-cell lymphoma (AITL).@*METHODS@#Sixty-one cases AITL diagnosed by Department of Pathology of Peking University Cancer Hospital were collected with their clinical data. Morphologically, they were classified as typeⅠ[lymphoid tissue reactive hyperplasia (LRH) like]; typeⅡ[marginal zone lymphoma(MZL)like] and type Ⅲ [peripheral T-cell lymphoma, not specified (PTCL-NOS) like]. Immunohistochemical staining was used to evaluate the presence of follicular helper T-cell (TFH) phenotype, proliferation of extra germinal center (GC) follicular dendritic cells (FDCs), presence of Hodgkin and Reed-Sternberg (HRS)-like cells and large B transformation. The density of Epstein-Barr virus (EBV) + cells was counted with slides stained by Epstein-Barr virus encoded RNA (EBER) in situ hybridization on high power field (HPF). T-cell receptor / immunoglobulin gene (TCR/IG) clonality and targeted exome sequencing (TES) test were performed when necessary. SPSS 22.0 software was used for statistical analysis.@*RESULTS@#Morphological subtype (%): 11.4% (7/61) cases were classified as type Ⅰ; 50.8% (31/61) as type Ⅱ; 37.8% (23/61) as type Ⅲ. 83.6% (51/61) cases showed classical TFH immunophenotype. With variable extra-GC FDC meshwork proliferation (median 20.0%); 23.0% (14/61) had HRS-like cells; 11.5% (7/61) with large B transformation. 42.6% (26/61) of cases with high counts of EBV. 57.9% (11/19) TCR+/IG-, 26.3% (5/19) TCR+/IG+, 10.5% (2/19) were TCR－/IG－, and 5.3% (1/19) TCR－/IG+. Mutation frequencies by TES were 66.7% (20/30) for RHOA, 23.3% (7/30) for IDH2 mutation, 80.0% (24/30) for TET2 mutation, and 33.3% (10/30) DNMT3A mutation. Integrated analysis divided into four groups: (1) IDH2 and RHOA co-mutation group (7 cases): 6 cases were type Ⅱ, 1 case was type Ⅲ; all with typical TFH phenotype; HRS-like cells and large B transformation were not found; (2) RHOA single mutation group (13 cases): 1 case was type Ⅰ, 6 cases were type Ⅱ, 6 cases were type Ⅲ; 5 cases without typical TFH phenotype; 6 cases had HRS-like cells, and 2 cases with large B transformation. Atypically, 1 case showed TCR－/IG－, 1 case with TCR－/IG+, and 1 case with TCR+/IG+; (3) TET2 and/or DNMT3A mutation alone group (7 cases): 3 cases were type Ⅱ, 4 cases were type Ⅲ, all cases were found with typical TFH phenotype; 2 cases had HRS-like cells, 2 cases with large B transformation, and atypically; (4) non-mutation group (3 cases), all were type Ⅱ, with typical TFH phenotype, with significant extra-GC FDC proliferation, without HRS-like cells and large B transformation. Atypically, 1 case was TCR－/IG－. Univariate analysis confirmed that higher density of EBV positive cell was independent adverse prognostic factors for both overall survival (OS) and progression free survival(PFS), (P=0.017 and P=0.046).@*CONCLUSION@#Pathological diagnoses of ALTL cases with HRS-like cells, large B transformation or type Ⅰ are difficult. Although TCR/IG gene rearrangement test is helpful but still with limitation. TES involving RHOA, IDH2, TET2, DNMT3A can robustly assist in the differential diagnosis of those difficult cases. Higher density of EBV positive cells counts in tumor tissue might be an indicator for poor survival.

Clinicopathological features and prognosis of anorectal melanoma: A report of 68 cases / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological characteristics of anorectal mucosal melanoma (ARMM), and to evaluate the prognostic factors.@*METHODS@#A total of 68 primary ARMM surgical specimens from 2010 to 2018 were retrospectively studied. Slides were reviewed to evaluate pathological features. Slingluff staging method was used for staging.@*RESULTS@#(1) Clinical features: The median age at diagnosis in this group was 61.5 years, with a male-to-female ratio 1 ∶1.62. The most common complaint was blooding (49 cases). For anatomic site, anorectum was the prevalent (66.2%), followed by rectum (20.6%). At the time of diagnosis, 28 cases were stage Ⅰ (localized stage, 41.2%), 25 cases were stage Ⅱ (regional lymph node metastasis, 36.8%), and 15 cases were stage Ⅲ (distant metastasis, 22.1%). Five patients underwent wide local excision, the rest abdominoperineal resection, and 48 patients received adjuvant therapy after surgery. (2) Pathological features: Grossly 88.2% of the tumors were exophytic polypoid masses, with the median tumor size 3.5 cm and the median tumor thickness 1.25 cm. Depth of invasion below lamina muscularis mucosae ranged from 0-5.00 cm (median 1.00 cm). The deepest site of tumor invasion reached muscular layer in 27 cases, and perirectal tissue in 16 cases. Melanin pigmentation was absent or not obvious in 67.6% of the cases. The predominant cytology was epithelioid (45 cases, 66.2%). The rate for ulceration, necrosis, lymphovascular invasion, and perineural invasion was 89.7%, 35.3%, 55.9%, and 30.9%, respectively. The median mitotic count was 18/mm2. The positive rate of S100, HMB-45 and Melan-A were 92.0%, 92.6% and 98.0%, respectively. The median of Ki-67 was 50%. The incidences of mutations within CKIT, BRAF and NRAS genes were 17.0% (9 cases), 3.8% (2 cases) and 9.4% (5 cases), respectively. (3) Prognosis: Survival data were available in 66 patients, with a median follow-up of 17 months and a median survival time of 17.4 months. The 1-year, 2-year and 5-year overall survival rate was 76.8%, 36.8% and 17.2%, respectively. The rate of lymphatic metastasis at diagnosis was 56.3%. Forty-nine patients (84.5%) suffered from distant metastasis, and the most frequent metastatic site was liver. Univariate analysis revealed that tumor size (>3.5 cm), depth of invasion below lamina muscularis mucosae (>1.0 cm), necrosis, lymphovascular invasion, BRAF gene mutation, lack of adjuvant therapy after surgery, deep site of tumor invasion, and high stage at diagnosis were all poor prognostic factors for overall survival. Multivariate model showed that lymphovascular invasion and BRAF gene mutation were independent risk factors for lower overall survival, and high stage at diagnosis showed borderline negative correlation with overall survival.@*CONCLUSION@#The overall prognosis of ARMM is poor, and lymphovascular invasion and BRAF gene mutation are independent factors of poor prognosis. Slingluff staging suggests prognosis effectively, and detailed assessment of pathological features, clear staging and genetic testing should be carried out when possible. Depth of invasion below lamina muscularis mucosae of the tumor might be a better prognostic indicator than tumor thickness.

Investigation on health status of workers exposed to glyphosate / 中华劳动卫生职业病杂志

Objective: To analyze the concentrations of glyphosate and its metabolites in occupational exposed workers and their possible effects on human health, so as to provide a reference for improving the safe use of glyphosate and toxicity research. Methods: From April to December 2020, 247 workers directly exposed to glyphosate in 5 enterprises were selected as the contact group, and 237 workers who were not exposed to glyphosate and other pesticides in the same enterprise were selected as the control group. Questionnaire survey and occupational health examination were conducted on objects, and the concentrations of glyphosate and its metabolites in the air of workplaces and biological samples were detected. The correlation between the concentrations and the difference of health examination between the two groups were analyzed. Results: The urine glyphosate concentration (0.022-47.668 mg/L), the rate of exceeding the standard (60.32%, 149/247) and the urine aminomethyl phosphonic acid concentration (<0.010-1.624 mg/L) in the contact group were higher than those in the control group [urine glyphosate concentration (<0.020-4.482 mg/L), the rate of exceeding the standard (2.53%, 6/237) and the urine aminomethyl phosphonic acid concentration (<0.010-0.524 mg/L) ], respectively (P<0.001). The exceeding standard rate of glyphosate concentration in the workplace was 33.67% (33/98). The concentration of glyphosate in the workplace was positively correlated with the concentrations of glyphosate and aminomethylphosphonic acid in urine (r(s)=0.804, 0.238, P<0.001), and the concentration of glyphosate in urine was positively correlated with the concentration of aminomethylphosphonic acid in urine (r(s)=0.549, P<0.001). The alanine aminotransferase (ALT), white cell ratio, creatinine, uric acid, the abnormal rates of ALT and total protein (TP) in the contact group were higher than those in the control group, and TP was lower than that in the control group, the differences were statistically different (P<0.05). The abnormal rates of overall liver function, overall renal function, blood routine test, urine routine test, electrocardiogram, liver B ultrasound and blood lipid in the contact group were significantly higher than those in the control group (P<0.05) . Conclusion: The concentration of glyphosate in the workplace is related to the concentrations of glyphosate and aminomethyl phosphonic acid in the urine of workers, and exposure to glyphosate may have some harmful effects on human health.

Study on preparation technology of long-acting sustained-release oral ulcer membrane based on analytic hierarchy process and orthogonal design / 药学实践杂志

Objective To prepare a sustained-release membrane with longer adhesion time and dissolution time, and compare it with the commercially available oral ulcer membrane. Method Adhesion strength, adhesion time, swelling coefficient, dissolution time, etc. were used as the inspection indicators, and a combination of single factor inspection and analytic hierarchy process were used to screen the membrane -forming materials. The dispersion method of clotrimazole, ornidazole and borneol were investigated to prevent the drug from seed out. The method of combining orthogonal experiment and analytic hierarchy process were used to optimize the dosage of CMC-Na, PVA-1788 and glycerin; and the commercial products were compared. Results Through single-factor investigation and orthogonal experiment, the optimal ratio of excipients was selected as CMC-Na∶PVA-1788∶glycerol (3∶1∶0.08). The water-insoluble component clotrimazole, ornidazole and borneol were treated by precipitation in liquid with good effect. The best method was used to prepare the membrane. The adhesion strength was 102 g. The adhesion time was 55 min. The swelling coefficient was 1 939.52. The average dissolution time was 110 min. The appearance was white and the surface was free of bubbles, soft and elastic. The membrane forming time at 60 ℃ was 300 min and the demolding effect was better which could be completely peeled off with moderate thickness. Conclusion The oral ulcer membrane developed in this method has good appearance, comfortable use, strong adhesion, long adhesion time and dissolution time, and could stay on the ulcer surface for a long time to form physical isolation, and slowly release the drug during the dissolution process, which could play the role of long-term pain relief, antibacterial, anti-inflammatory and promote healing effects on oral ulcers.