Elevation of artemisinin content by co-transformation of artemisinin biosynthetic pathway genes and trichome-specific transcription factors in Artemisia annua.

Artemisinin, derived from Artemisia annua, is currently used as the first-line treatment for malaria. However, wild-type plants have a low artemisinin biosynthesis rate. Although yeast engineering and plant synthetic biology have shown promising results, plant genetic engineering is considered the most feasible strategy, but it is also constrained by the stability of progeny development. Here we constructed three independent unique overexpressing vectors harboring three mainstream artemisinin biosynthesis enzymes HMGR, FPS, and DBR2, as well as two trichomes-specific transcription factors AaHD1 and AaORA. The simultaneous co-transformation of these vectors by Agrobacterium resulted in the successful increase of the artemisinin content in T0 transgenic lines by up to 3.2-fold (2.72%) leaf dry weight compared to the control plants. We also investigated the stability of transformation in progeny T1 lines. The results indicated that the transgenic genes were successfully integrated, maintained, and overexpressed in some of the T1 progeny plants' genomes, potentially increasing the artemisinin content by up to 2.2-fold (2.51%) leaf dry weight. These results indicated that the co-overexpression of multiple enzymatic genes and transcription factors via the constructed vectors provided promising results, which could be used to achieve the ultimate goal of a steady supply of artemisinin at affordable prices around the world.

Selection of statistical methods for estimating the association between exposure factors and rare outcomes based on cohort studies / 中华流行病学杂志

Odds ratio (OR) and relative risk (RR) are the most commonly used statistical indicators for the estimation of the association between exposure and outcome. In the cohort study with rare outcomes, the estimated OR approximately equals RR, but RR seems more interpretable. The study aims to explore the difference between OR and RR estimated by different multivariate analyses to provide reference for the selection of more appropriate multivariate regression methods and reporting indicators for estimating the association between exposure and rare outcome in cohort studies. This case study used the data from China birth cohort study. Modes of conception and congenital disabilities were regarded as exposure and outcome, respectively. Maternal age, family history of congenital disabilities with clear evidence were included as covariates. Logistic regression, log-binomial regression, and Poisson regression were used to estimate the OR and RR, respectively. Then, OR, RR, and their 95%CI estimated by three regression models were compared. The OR estimated by logistic regression was approximately equal to the RR estimated by log-binomial regression or Poisson regression. However, the RR estimated by log-binomial regression or Poisson regression was closer to 1.00, with a narrower 95%CI. Log-binomial regression or Poisson regression might have non convergence or over dispersion problems. It is recommended to report the RR obtained by log-binomial regression or Poisson regression in the cohort study with rare outcomes if applicable.

Effectiveness of temporal island flap pedicled with perforating branch of zygomatic orbital artery to repair the defects after periocular malignant tumor resection / 中国修复重建外科杂志

OBJECTIVE@#To summarize the effectiveness of the temporal island flap pedicled with the perforating branch of zygomatic orbital artery for repairing defects after periocular malignant tumor resection.@*METHODS@#Between January 2015 and December 2020, 15 patients with periocular malignant tumors were treated. There were 5 males and 10 females with an average age of 62 years (range, 40-75 years). There were 12 cases of basal cell carcinoma and 3 cases of squamous carcinoma. The disease duration ranged from 5 months to 10 years (median, 2 years). The size of tumors ranged from 1.0 cm×0.8 cm to 2.5 cm×1.5 cm, without tarsal plate invasion. After extensive resection of the tumors, the left defects in size of 2.0 cm×1.5 cm to 3.5 cm×2.0 cm were repaired with the temporal island flap pedicled with the perforating branch of zygomatic orbital artery via subcutaneous tunnel. The size of the flaps ranged from 3.0 cm×1.5 cm to 5.0 cm×2.0 cm. The donor sites were separated subcutaneously and sutured directly.@*RESULTS@#All flaps survived after operation and the wounds healed by first intention. The incisions at donor sites healed by first intention. All patients were followed up 6-24 months (median, 11 months). The flaps were not obviously bloated, the texture and color were basically the same as the surrounding normal skin, and the scars at recipient sites were not obviously. There was no complication such as ptosis, ectropion, or incomplete closure of the eyelids and recurrence of tumor during follow-up.@*CONCLUSION@#The temporal island flap pedicled with the perforating branch of zygomatic orbital artery can repair the defects after periorbital malignant tumors resection and has the advantages of reliable blood supply, flexible design, and good morphology and function.

Radiomics based on biparametric MRI for the detection of significant residual prostate cancer after androgen deprivation therapy: using whole-mount histopathology as reference standard / 亚洲男科学杂志(英文版)

We aimed to study radiomics approach based on biparametric magnetic resonance imaging (MRI) for determining significant residual cancer after androgen deprivation therapy (ADT). Ninety-two post-ADT prostate cancer patients underwent MRI before prostatectomy (62 with significant residual disease and 30 with complete response or minimum residual disease [CR/MRD]). Totally, 100 significant residual, 52 CR/MRD lesions, and 70 benign tissues were selected according to pathology. First, 381 radiomics features were extracted from T2-weighted imaging, diffusion-weighted imaging, and apparent diffusion coefficient (ADC) maps. Optimal features were selected using a support vector machine with a recursive feature elimination algorithm (SVM-RFE). Then, ADC values of significant residual, CR/MRD lesions, and benign tissues were compared by one-way analysis of variance. Logistic regression was used to construct models with SVM features to differentiate between each pair of tissues. Third, the efficiencies of ADC value and radiomics models for differentiating the three tissues were assessed by area under receiver operating characteristic curve (AUC). The ADC value (mean ± standard deviation [s.d.]) of significant residual lesions ([1.10 ± 0.02] × 10-3 mm2 s-1) was significantly lower than that of CR/MRD ([1.17 ± 0.02] × 10-3 mm2 s-1), which was significantly lower than that of benign tissues ([1.30 ± 0.02] × 10-3 mm2 s-1; both P < 0.05). The SVM feature models were comparable to ADC value in distinguishing CR/MRD from benign tissue (AUC: 0.766 vs 0.792) and distinguishing residual from benign tissue (AUC: 0.825 vs 0.835) (both P > 0.05), but superior to ADC value in differentiating significant residual from CR/MRD (AUC: 0.748 vs 0.558; P = 0.041). Radiomics approach with biparametric MRI could promote the detection of significant residual prostate cancer after ADT.

Mechanism of Cryptotanshinone Inhibiting Proliferation of Human Breast Cancer MCF7 Cells / 肿瘤防治研究

Objective To investigate the inhibitory effect of cryptotanshinone (CPT) on human breast cancer cell MCF7 and its mechanism. Methods The survival rate of MCF7 cells was measured by MTT assay. Cell apoptosis was detected by Annexin V/PI assay and Hoechst 33258 fluorescence staining assay. Cell cycle and reactive oxygen species were detected by flow cytometry. Cell migration and invasion were detected by cell scratch test and Transwell chamber test. The surface molecules CD44 and CD24 were detected by flow cytometry and microsphere culture. The expression of cell-associated proteins was detected by Western blot. Results CPT inhibited the proliferation of MCF7 cells in a dose-dependent manner, and the 24 h IC50 value was 19.24 μmol/L. Compared with the untreated group, the CPT-treated group showed cell cycle arrested in the S phase, and apoptosis was induced. The results of the cell scratch and Transwell chamber tests showed that CPT significantly inhibited the migration and invasion of MCF7 cells. Furthermore, CPT reduced the CD24-/LowCD44+ cell population in MCF7 cell-derived microspheres. Western blot results showed that CPT could up-regulate the expression of Bax protein, down-regulate the expression of BCL-2, PI3K-p85, Akt, N-cadherin, Twist1, Sox2, Oct4, and Nanog protein, effectively inhibit the phosphorylation of ER-α, and decrease the expression of ABCG2. Conclusion CPT can inhibit the proliferation of MCF7 cells by inhibiting the migration and invasion of MCF7 cells, decreasing the number of CD24-/lowCD44+ cells and affecting the expression of tumor stem cell-related proteins.

A novel technique of pure transperitoneal laparoscopic nephroureterectomy at a single position for native upper tract urothelial carcinoma in ipsilateral renal transplant recipients / 中华器官移植杂志

Objective:To explore the techniques and outcomes of pure laparoscopic native nephroureterectomy (LNUT) with ipsilateral allograft at a single position for upper tract urothelial carcinoma (UTUC) in renal transplant (RT) recipients.Methods:Clinical data were retrospectively reviewed for 12 renal transplant children undergoing native UTUC with ipsilateral allograft from January 2016 to December 2021.There were 4 boys and 8 girls.Complete LNUT was performed with bladder cuff resection at a single position via a transperitoneal approach.The interval between UTUC and RT was 12-146 months.There were 6 pelvic UCs and 6 ureter UCs.Results:All laparoscopic procedures were successfully completed without any serious perioperative complication.Postoperative pathological examination confirmed the diagnosis of urothelial carcinoma.And all surgical margins were negative.One patient experienced an elevation of creatinine after one cycle chemotherapy and normalized after withdrawing chemotherapy.The median follow-up period was (4-65) month.Two cases of contralateral native transitional cell carcinoma had radical nephroureterectomy two years later and another two cases underwent transurethral resection of bladder tumor one year later.One case died from tumor metastasis.The remainders had no tumor recurrence or metastasis during follow-ups.Conclusions:Complete single-position LNUT for UTUC with ipsilateral allograft is a safe and effective mini-invasive technique.Effectively avoiding the injury of allograft, it also offers the advantages of standard operation, minimal trauma, simple handling and enhanced recovery after surgery (ERAS).

Clinical features and risk factors of recurrent acute pancreatitis / 中华胰腺病杂志

Objective:To explore the clinical characteristics and to analyze the risk factors of recurrent acute pancreatitis (RAP).Methods:The clinical data of 3 022 patients with AP from AP database of the Affiliated Hospital of Southwest Medical University between January 2013 and December 2019 were retrospectively analyzed. According to with or without AP relapse and RAP diagnostic criteria, the patients were divided into initial group ( n=2 187) and recurrent group ( n=835). General characteristics, clinical data, and prognostic indicators were compared between the two groups. Multivariate logistic regression analysis was used to explore the risk factors of RAP. Results:The proportion of men, previous biliary disease, hyperlipidemia, diabetes mellitus and previous gallbladder or biliary surgery in recurrent group were significantly higher, while the mean age was significantly lower than that of the initial group. The main causes in the initial group successively were biliary disorders, hyperlipidemia and alcohol, while in the recurrent group were hyperlipidemia, biliary disorders and alcohol. The etiology of hyperlipidemia was significantly higher in the recurrent group than in initial group. The incidence of MAP and regional portal hypertension was significantly higher in the recurrent group, while the incidence of SAP and acute respiratory distress syndrome were significantly lower than those in the initial group, and all the differences were statistically significant(All P value <0.001). The results of the correlation analysis showed that there was no correlation between the severity of RAP and the number of recurrence, and the risk of SAP in RAP did not decrease with the increasing number of recurrence. The results of the multivariate logistic regression analysis showed that previous biliary disorders ( OR=1.303, 95% CI 1.032-1.645, P=0.026), previous history of hyperlipidemia ( OR=2.631, 95% CI 1.580-4.379, P<0.001), and the etiology of hyperlipidemia ( OR=1.773, 95% CI 1.465-2.145, P<0.001) were independent risk factors for RAP. Conclusions:RAP may often occur in middle-aged men and hyperlipidemia is the main cause of RAP, previous history of hyperlipidemia and biliary disease are risk factors for RAP.

Preclinical evaluation of RQ3013, a broad-spectrum mRNA vaccine against SARS-CoV-2 variants

The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike(S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the Wild-type, B.1.1.7, B.1.351, B.1.617.2, and the omicron B.1.1.529 variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. We also proved the safety of RQ3013 in NHP models. Our results provided key support for the evaluation of RQ3013 in clinical trials.

Preferential expansion of cross-reactive pre-existing switched memory B cells that recognize the SARS-CoV-2 Omicron variant Spike protein

In previously unvaccinated and uninfected individuals, non-RBD SARS-CoV-2 spike-specific B cells were prominent in two distinct, durable, resting, cross-reactive, "pre-existing" switched memory B cell compartments. While pre-existing RBD-specific B cells were extremely rare in uninfected and unvaccinated individuals, these two pre-existing switched memory B cell compartments were molded by vaccination and infection to become the primary source of RBD-specific B cells that are triggered by vaccine boosting. The frequency of wild-type RBD-binding memory B cells that cross-react with the Omicron variant RBD did not alter with boosting. In contrast, after a boost, B cells recognizing the full-length Omicron variant spike protein expanded, with pre-existing resting memory B cells differentiating almost quantitatively into effector B cell populations. B cells derived from "ancient" pre-existing memory cells and that recognize the full-length wild-type spike with the highest avidity after boosting are the B cells that also bind the Omicron variant spike protein. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/21268554v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1de97acorg.highwire.dtl.DTLVardef@b7ab7forg.highwire.dtl.DTLVardef@5c38dcorg.highwire.dtl.DTLVardef@99106c_HPS_FORMAT_FIGEXP M_FIG C_FIG

Inhibitory effects and mechanisms of cryptotanshinone on the growth of tamoxifen resistant breast cancer cells / 药学学报

This study investigated the inhibitory effect and mechanisms of cryptotanshinone (CPT) on tamoxifen resistant cell MCF7-TAMR. The inhibitory effect of CPT on the viability of MCF7-TAMR cells was evaluated using the MTT assay. We found that CPT significantly inhibited the growth of MCF7-TAMR cells in a dose- and time-dependent manner. The half inhibitory concentration (IC50) is 15.14 ± 2.82 μmol·L-1 at 24 h. CPT induced cell cycle arrest of MCF7-TAMR cells at G0/G1 phase, and promoted apoptosis of MCF7-TAMR cells by upregulating intracellular levels of reactive oxygen species (ROS). Transwell results showed that CPT significantly inhibited the migration of MCF7-TAMR cells. Furthermore, CPT decreased the CD24-/lowCD44+ cell population in MCF7-TAMR cell-derived microspheres. Western blot results showed that CPT effectively inhibited the phosphorylation of estrogen receptor α (ER-α), and reduced the expression of phosphatidylinositol 3-kinase (PI3K-p85), serine-threonine protein kinase (Akt) and multidrug transporter ATP-binding cassette superfamily G member 2 (ABCG2). These results showed that CPT can induce cell apoptosis, cause cell cycle arrest, inhibit cell migration and inhibit ER-α phosphorylation, inhibit PI3K/Akt signaling pathway, reduce the number of CD24-/lowCD44+ cells and the expression of ABCG2, overcome cell drug resistance.

Simultaneous determination of ten phenols in Polygoni Cuspidati Rhizoma by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry / 国际中医中药杂志

Objective:This study aimed to determinate ten phenols (polydatin, resveratrol, rhein, emodin, chrysophanol, physcion, oxyresveratrol, 2,3,5,4'-tetera-hydroxystilbene-2-O-β-D-glucoside, (＋)-catechin and (-)-epicatechin) in Polygoni Cuspidati Rhizoma simultaneously based on the high-resolution multiple reaction monitoring (MRMHR) mode of ultra- performance liquid chromatography- quadrupole/time-of-flight mass spectrometry. Methods:The assay was performed on Waters ACQUITY UPLC BEH C18 (2.1 mm× 100 mm, 1.7 μm) column using acetonitrile-0.1% formic acid as the mobile phase. The flow rate was 0.2 ml/min. The MRMHR mode was adopted for quantification.Results:The analyzed compounds showed good linearity relationships ( r2>0.999). The intra- and inter-batch relative standard deviations were all <5% and the recovery rate was between 96.28%-103.23%. The content of polydatin was the highest, followed by resveratrol and emodin. However, the contents of chrysophanol and oxyresveratrol were relatively low and some batches were unqualified. The contents of analyzed compounds varied significantly among the ten batches. Conclusion:The proposed UPLC-Q/TOF-MS method was successfully established to determinate ten phenols in Polygoni Cuspidati Rhizoma simultaneously, which could provide technical support for the quality evaluation of Polygonum cuspidatum.

Vaccine serologic responses among transplant patients associate with COVID-19 infection and T peripheral helper cells

BackgroundTherapeutically immunosuppressed transplant recipients exhibit attenuated responses to COVID-19 vaccines. To better understand the immune alterations that determined poor vaccine response, we correlated quantities of circulating T and B cell subsets at baseline with longitudinal serologic responses to SARS-CoV-2 mRNA vaccination in heart and lung transplant recipients. MethodsSamples at baseline and at approximately 8 and 30 days after each vaccine dose for 22 heart and lung transplant recipients with no history of COVID-19, four heart and lung transplant recipients with prior COVID-19 infection, and 12 healthy controls undergoing vaccination were analyzed. Anti-spike protein receptor binding domain (RBD) IgG and pseudovirus neutralization activity were measured. Proportions of B and T cell subsets at baseline were comprehensively quantitated. ResultsAt 8-30 days post vaccination, healthy controls displayed robust anti-RBD IgG responses, whereas heart and lung transplant recipients showed minimally increased responses. A parallel absence of activity was observed in pseudovirus neutralization. In contrast, three of four (75%) transplant recipients with prior COVID-19 infection displayed robust responses at levels comparable to controls. Baseline levels of activated PD-1+ HLA-DR+ CXCR5- CD4+ T cells (also known as T peripheral helper [TPH] cells) and CD4+ T cells strongly predicted the ability to mount a response. ConclusionsImmunosuppressed patients have defective vaccine responses but can be induced to generate neutralizing antibodies after SARS-CoV-2 infection. Strong correlations of vaccine responsiveness with baseline TPH and CD4+ T cell numbers highlights a role for T helper activity in B cell differentiation into antibody secreting cells during vaccine response.

Expansion of Cytotoxic CD4+ T cells in the lungs in severe COVID-19

The contributions of T cells infiltrating the lungs to SARS-CoV-2 clearance and disease progression are poorly understood. Although studies of CD8+ T cells in bronchoalveolar lavage and blood have suggested that these cells are exhausted in severe COVID-19, CD4+ T cells have not been systematically interrogated within the lung parenchyma. We establish here that cytotoxic CD4+ T cells (CD4+CTLs) are prominently expanded in the COVID-19 lung infiltrate. CD4+CTL numbers in the lung increase with disease severity and progression is accompanied by widespread HLA-DR expression on lung epithelial and endothelial cells, increased apoptosis of epithelial cells and tissue remodeling. Based on quantitative evidence for re-activation in the lung milieu, CD4+ CTLs are as likely to drive viral clearance as CD8+ T cells and may also be contributors to lung inflammation and eventually to fibrosis in severe COVID-19. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/21253885v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@198a382org.highwire.dtl.DTLVardef@16b3cdorg.highwire.dtl.DTLVardef@769032org.highwire.dtl.DTLVardef@1f4cd1c_HPS_FORMAT_FIGEXP M_FIG C_FIG In BriefIn severe COVID-19 cytotoxic CD4+ T cells accumulate in draining lymph nodes and in the lungs during the resolving phase of the disease. Re-activated cytotoxic CD4+ T cells and cytotoxic CD8+ T cells are present in roughly equivalent numbers in the lungs at this stage and these cells likely collaborate to eliminate virally infected cells and potentially induce fibrosis. A large fraction of epithelial and endothelial cells in the lung express HLA class II in COVID-19 and there is temporal convergence between CD4+CTL accumulation and apoptosis in the lung. HighlightsO_LIIn severe COVID-19, activated CD4+ CTLs accumulate in the lungs late in disease C_LIO_LIThese cells likely participate in SARS-CoV-2 clearance, collaborating with CD8+ T cells many of which exhibit an exhausted phenotype C_LIO_LIT cells likely contribute to the late exacerbation of inflammation C_LIO_LICD4+CTLs have been linked to fibrosis in many disorders and could also be responsible for the eventual induction of fibrosis in a subset of COVID-19 patients C_LI SummaryThe contributions of T cells infiltrating the lungs to SARS-CoV-2 clearance and disease progression are poorly understood. Although studies of CD8+ T cells in bronchoalveolar lavage and blood have suggested that these cells are exhausted in severe COVID-19, CD4+ T cells have not been systematically interrogated within the lung parenchyma. We establish here that cytotoxic CD4+ T cells (CD4+CTLs) are prominently expanded in the COVID-19 lung infiltrate. CD4+CTL numbers in the lung increase with disease severity and progression is accompanied by widespread HLA-DR expression on lung epithelial and endothelial cells, increased apoptosis of epithelial cells and tissue remodeling. Based on quantitative evidence for re-activation in the lung milieu, CD4+ CTLs are as likely to drive viral clearance as CD8+ T cells and may also be contributors to lung inflammation and eventually to fibrosis in severe COVID-19.

Screening of Differential Genes for Endometriosis and Expression Validation of the Potential Target GAS6 / 中国生物化学与分子生物学报

Growth arrest specific protein 6 (GAS6) plays an important role in the occurrence and development of tumors, and its signal transduction is involved in cell proliferation, adhesion and migration, but its related functions and molecular mechanisms in endometriosis (EMs) are still unclear. In this study, we searched and downloaded the transcriptome datasets of EMs from GEO database and performed GEO online analysis, and then screened out the differentially expressed genes and performed cluster analysis based on GO and KEGG pathway. The mRNA levels of the differentially expressed genes shared by more than three datasets were verified by qRT-PCR in the endometrium of ten women with no endometriosis and no clear disease and the ectopic endometrium of 11 patients with ovarian chocolate cysts. Immunohistochemistry and qRT-PCR were used to verify the expression of GAS6 and epithelial mesenchymal transition (EMT) marker genes, and immunofluorescence was used to co-label GAS6 and E-cadherin in endometriosis clinical samples. In this study, a total of 47 differentially expressed genes were screened out of the four transcriptome datasets, which were mainly enriched in processes such as cell migration and related signal pathways such as MAPK, PI3K-AKT, and tight junction. The mRNA levels of the nine differentially expressed genes shared by more than three datasets in endometriosis patients were consistent with the results of bioinformatics analysis. GAS6 expression levels in ectopic endometrium of EMs patients are higher than the control group (P < 0. 05), and EMs patients have the characteristics of EMT in the ectopic endometrial tissue, that is, the expression of E-cadherin is down-regulated (P < 0. 05) and the expression of vimentin is up-regulated (P < 0. 01). The expression of E-cadherin in the ectopic endometrial glandular epithelial cells of EMs patients is low while the expression of GAS6 is up-regulated, suggesting that GAS6 may mediate the EMT process in endometriosis. In conclusion, this study reveals that GAS6 is highly expressed in endometriosis patients and may mediate the EMT process to participate in the occurrence and development of endometriosis, providing a potential target for clinical treatment of endometriosis.

Naringenin protects ischemia-reperfusion-induced acute kidney injury by nuclear factor κB / 中华肾脏病杂志

Objective:To explore the effect and involved mechanism of naringenin on acute kidney injury (AKI) induced by ischemia-reperfusion (IR).Methods:The IR-AKI rat model was constructed using the classic bilateral renal pedicle clamping method, then renal function and pathological change were assessed, as well as inflammation-associated genes were detected by quantitative real-time PCR. The hub genes were selected through differential gene analysis and protein-protein interaction network analysis, and their transcription factors were predicted, which constructed a protein library together. The proteins binding to naringenin were selected by reverse molecular docking analysis and further their binding patterns were predicted to explore the mechanism of naringenin. Finally, the results of bioinformatics were verified by experimental methods.Results:Compared with the AKI group, the kidney pathology of the rats in the naringenin pretreatment group was significantly improved, and the renal tubular injury score was reduced ( P<0.01); meanwhile the serum creatinine level and the mRNA expression of the kidney injury molecule 1 (KIM-1) were significantly decreased (both P<0.05). Compared to sham group, IR-AKI increased the level of nuclear factor κB (NF-κB), tumor necrosis factor-α and interleukin-1β (all P<0.05), which reversed by naringenin indicated that naringenin inhibited inflammation in IR-AKI. Differential gene analysis was performed on the GSE98622 data set, and 359 differential genes were obtained. In reverse molecular docking, the proteins with smallest binding energy including NFKBIA, BCL3, NFKB2 and RELA were considered to be related to the preventive effect of naringenin, which were mainly enriched in NF-κB-related inflammation pathways. Domain functional analysis of NF-κB-related genes showed that naringenin could stably bind to its key domain. According to quantitative real-time PCR results, naringenin increased BCL3 level after AKI ( P<0.05), and further decreased the expression level of RELA and NFKB2 (both P<0.05). Conclusion:Naringenin protects IR-AKI by alleviating inflammation, and its mechanism is related to increasing BCL3 and thereby inhibiting the NF-κB pathway.

Research progress of STAT3 inhibitors / 药学实践杂志

Signal transducer and activator of transcription 3 (STAT3) is a signal transcription protein that exists in the cytoplasm. The abnormal activation of STAT3 is closely related to cell proliferation, differentiation, and canceration. It has abnormal expression in cancer stem cells such as breast cancer, pancreatic cancer, lymphoma, and lung cancer. Therefore, inhibiting the abnormal expression of STAT3 has become a new approach for antitumor therapy.

Synthesis of the active ingredient rosavin of Rhodiola rosea / 药学实践杂志

Objective To establish the chemical synthesis of the active ingredient rosavin of Rhodiola rosea. Methods β-D-pentaacetylglucose, 1-hydroxy-2,3,4-triacetylarabinose and cinnamyl alcohol were used as starting materials. The target compound was prepared by 1-position selective of β-D-pentaacetylglucose deacetylation, glycosylation reaction, glucose 6-OH selective protection and deprotection and other 8-step reactions. Results The target product, rosavage, was successfully obtained with high yield. The structure was confirmed by ESI-MS, 1H-NMR and 13C-NMR. The protection of 6-OH with high selectivity and high yield of tert-butyldiphenyl chlorosilane played a vital role in the synthesis process,. Conclusion The synthetic route has the advantages of simple operation, high yield, and good safety.

Periprostatic fat thickness measured on MRI correlates with lower urinary tract symptoms, erectile function, and benign prostatic hyperplasia progression / 亚洲男科学杂志(英文版)

This study investigated the correlation between periprostatic fat thickness (PPFT) measured on magnetic resonance imaging and lower urinary tract symptoms, erectile function, and benign prostatic hyperplasia (BPH) progression. A total of 286 treatment-naive men diagnosed with BPH in our department between March 2017 and February 2019 were included. Patients were divided into two groups according to the median value of PPFT: high (PPFT >4.35 mm) PPFT group and low (PPFT <4.35 mm) PPFT group. After the initial evaluation, all patients received a combination drug treatment of tamsulosin and finasteride for 12 months. Of the 286 enrolled patients, 244 completed the drug treatment course. Patients with high PPFT had larger prostate volume (PV; P = 0.013), higher International Prostate Symptom Score (IPSS; P = 0.008), and lower five-item version of the International Index of Erectile Function (IIEF-5) score (P = 0.002) than those with low PPFT. Both high and low PPFT groups showed significant improvements in PV, maximum flow rate, IPSS, and quality of life score and a decrease of IIEF-5 score after the combination drug treatment. The decrease of IIEF-5 score was more obvious in the high PPFT group than that in the low PPFT group. In addition, more patients in the high PPFT group underwent prostate surgery than those in the low PPFT group. Moreover, Pearson's correlation coefficient analysis indicated that PPFT was positively correlated with age, PV, and IPSS and negatively correlated with IIEF-5 score; however, body mass index was only negatively correlated with IIEF-5 score.

Worldwide tracing of mutations and the evolutionary dynamics of SARS-CoV-2

Understanding the mutational and evolutionary dynamics of SARS-CoV-2 is essential for treating COVID-19 and the development of a vaccine. Here, we analyzed publicly available 15,818 assembled SARS-CoV-2 genome sequences, along with 2,350 raw sequence datasets sampled worldwide. We investigated the distribution of inter-host single nucleotide polymorphisms (inter-host SNPs) and intra-host single nucleotide variations (iSNVs). Mutations have been observed at 35.6% (10,649/29,903) of the bases in the genome. The substitution rate in some protein coding regions is higher than the average in SARS-CoV-2 viruses, and the high substitution rate in some regions might be driven to escape immune recognition by diversifying selection. Both recurrent mutations and human-to-human transmission are mechanisms that generate fitness advantageous mutations. Furthermore, the frequency of three mutations (S protein, F400L; ORF3a protein, T164I; and ORF1a protein, Q6383H) has gradual increased over time on lineages, which provides new clues for the early detection of fitness advantageous mutations. Our study provides theoretical support for vaccine development and the optimization of treatment for COVID-19. We call researchers to submit raw sequence data to public databases.

Acetabular reaming and sartorius muscle pedicle iliac bone grafting in the treatment of developmental dysplasia of the hip in older children: a retrospective study of 15 patients with more than two years follow-up.

PURPOSE: Despite the early diagnosis and treatment of developmental dysplasia of the hip (DDH), some older children still need open reduction. It is usually difficult to get a satisfactory reduction particularly in patients with acetabular defect. The purpose of this study was to evaluate the short-term outcomes of acetabulum reaming and sartorius muscle pedicle iliac bone grafting in the treatment of older children with DDH and acetabular defect. METHODS: The records of 15 patients with DDH (mean age 113.9 months (sd 29); 17 hips) who were treated with the reported technique between February 2015 and January 2017 were retrospectively reviewed. All patients acquired regular clinical and radiographic follow-ups, and alterations in the acetabular index, centre-edge angle and acetabular head index were measured. Joint function and radiographic results were evaluated with McKay and Severin modified criteria, respectively. RESULTS: A total of 15 patients were followed up for mean 32.4 months (sd 6.9). The percentages of excellent and good conditions were 94.1% (16/17) according to the Severin modified criteria and 88.2% (15/17) according to the McKay modified criteria. Avascular necrosis of the femoral head and redislocation only occurred in one hip. No cases of ankylosis or bone graft absorption occurred during the follow-up. CONCLUSION: Reaming the acetabulum and sartorius muscle pedicle iliac bone grafting for repairing the acetabular defect can recover the arcuate structure by increasing the volume of the acetabulum, which is beneficial for achieving a concentric reduction. The short-term outcome was satisfactory, while the long-term results need to be further observed. LEVEL OF EVIDENCE: IV - retrospective study.