Multidimensional evaluation of teaching strategies for pharmacology based on a comprehensive analysis involving 21,269 students.

Background: Given the limitations of traditional pharmacology pedagogical method, diverse novel teaching methods have been widely explored. In this study, we performed a network meta-analysis (NMA) to evaluate the effects of different strategies in pharmacology education. Methods: Literature databases were searched from their inception to November 2022, and the studies were screened according to predefined inclusion and exclusion criteria to extract important information. Outcomes, including theoretical test scores, experimental test scores, subjective test scores, satisfaction scores, and the proportion of satisfaction, were analyzed using R software (version 3.6.1) and STATA (version 15). The NMA was conducted with a random-effects model under the Bayesian framework to calculate odds ratios (ORs) or mean differences (MDs) with associated 95% credible intervals (95% CIs). Surface under the cumulative ranking curve (SUCRA) probability values were calculated to rank the teaching methods examined. Results: A total of 150 studies involving 21,269 students were included. This NMA systematically evaluated 24 teaching strategies, such as problem-based learning (PBL), team-based learning (TBL), case-based learning (CBL) and flipped classrooms (FC), etc., The results of the NMA showed that, PBL combined with CBL was most likely to improve students' theoretical and subjective test scores (SUCRA = 75.49 and 98.19%, respectively), TBL was most likely to improve the experimental test score (SUCRA = 92.38%) and the satisfaction score (SUCRA = 88.37%), while FC had the highest probability of being the best option for improving the proportion of satisfaction (SUCRA = 84.45%). Conclusion: The current evidence indicates that TBL, PBL combined with CBL, and FC might be optimal strategies for pharmacology education since they have a more beneficial effect on students.

Magnesium Isoglycyrrhizinate Attenuates Anti-Tuberculosis Drug-Induced Liver Injury by Enhancing Intestinal Barrier Function and Inhibiting the LPS/TLRs/NF-κB Signaling Pathway in Mice.

Liver injury caused by first-line anti-tuberculosis (anti-TB) drugs accounts for a high proportion of drug-induced liver injury (DILI), and gut microbiota and intestinal barrier integrity have been shown to be involved in the development of DILI. Magnesium isoglycyrrhizinate (MgIG) is the fourth-generation glycyrrhizic acid preparation, which is well documented to be effective against anti-TB DILI, but the underlying mechanism is largely unclear. In the present study, we established a BALB/c mice animal model of the HRZE regimen (39 mg/kg isoniazid (H), 77 mg/kg rifampicin (R), 195 mg/kg pyrazinamide (Z), and 156 mg/kg ethambutol (E))-induced liver injury to investigate the protective effect of MgIG against anti-TB DILI and underlying mechanisms. The results demonstrated that intraperitoneal injection of MgIG (40 mg/kg) significantly ameliorated HRZE-induced liver injury by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), and malondialdehyde (MDA) levels and improved liver pathological changes. Species composition analysis of gut microbiota showed that Lactobacillus was the only probiotic that was down-regulated by HRZE and recovered by MgIG. In addition, MgIG attenuated HRZE-induced intestinal pathology, significantly decreased HRZE-induced intestinal permeability by increasing the protein expression of tight junction protein 1 (ZO-1) and occludin, decreased HRZE-induced high lipopolysaccharide (LPS) levels, and further markedly attenuated mRNA expression levels of TNF-α, IL-6, TLR2, TLR4, and NF-κB. Supplementation with Lactobacillus rhamnosus JYLR-005 (>109 CFU/day/mouse) alleviated HRZE-induced liver injury and inflammation in mice. In summary, MgIG effectively ameliorated HRZE-induced liver injury by restoring the abundance of Lactobacillus, enhancing intestinal barrier function, and further inhibiting the activation of the LPS/TLRs/NF-κB signaling pathway. Regulating gut microbiota and promoting the integrity of intestinal barrier function may become a new direction for the prevention and treatment of anti-TB DILI.

[Isolation and identification of a new phytopathogen causing root rot of Rehmannia glutinosa].

Root rot was occurred widely in the production area of Rehmannia glutinosa, and which result in serious influence on the yield and quality of R. glutinosa. In the present work, a new phytopathogen was isolated from roots with root rot symptom in the production area of R. glutinosa. The colony of the pathogen growing on PDA medium was gray-black, the structure of hyphae was compact, the aerial hyphae was less developed, and the back of the colony was black. The hyphae of the pathogen were uneven in size, about 2 to 3 µm in diameter and twined with each other, the conidia of the pathogen were small, nearly round and about 1 µm in diameter. The healthy roots of R. glutinosa were inoculated with the pathogen in vitro, black-brown rot was observed at the inoculate sites after a few days' incubation. The rhizosphere soil of healthy R. glutinosa seedlings were inoculated in vivo, the leaves were wilted and the roots were black-brown rotted after several days' normal culture, the symptoms were consistent with those observed in the field. The genomic DNA of the pathogen was amplified by fungus rDNA-ITS universal primer ITS1/ITS4 and homologous analyzed, the pathogen was in a branch with Heterophoma sp., Phoma sp., P. novae-verbascicola and P. herbarum with the nuclear acid homology of 99.21% to 99.43%. The pathogen shown 97.00% to 98.02% nuclear acid homology with H. verbascicola, H. novae-verbascicola, H. poolensis, P. herbarum, H. sylvatica, H. verbascicola and H. verbasci-densiflori when amplified by the tub2 gene special primer Btub2 fd/Btub4 rd, and H. novae-verbascicola was the highest. The pathogen was in a branch with H. novae-verbascicola when amplified by the lsu gene special primer LR0 R/LR7. Based on the morphological characteristics, nucleotide sequence analysis and Koch's test results, the isolated pathogen causing root rot of R. glutinosa was identified as H. novae-verbascicola. This study is of great significance for the further theoretical research on root rot of R. glutinosa and root rot control in field.

Pharmacomicrobiomics: Exploiting the Drug-Microbiota Interactions in Antihypertensive Treatment.

Hypertension is a leading risk factor for cardiovascular diseases and can reduce life expectancy. Owing to the widespread use of antihypertensive drugs, patients with hypertension have improved blood pressure control over the past few decades. However, for a considerable part of the population, these drugs still cannot significantly improve their symptoms. In order to explore the reasons behind, pharmacomicrobiomics provide unique insights into the drug treatment of hypertension by investigating the effect of bidirectional interaction between gut microbiota and antihypertensive drugs. This review discusses the relationship between antihypertensive drugs and the gut microbiome, including changes in drug pharmacokinetics and gut microbiota composition. In addition, we highlight how our current knowledge of antihypertensive drug-microbiota interactions to develop gut microbiota-based personalized ways for disease management, including antihypertensive response biomarker, microbial-targeted therapies, probiotics therapy. Ultimately, a better understanding of the impact of pharmacomicrobiomics in the treatment of hypertension will provide important information for guiding rational clinical use and individualized use.

First-Line Pazopanib Treatment in Metastatic Renal Cell Carcinoma: Real-World Data From a Single Chinese Center.

The response to pazopanib in patients with metastatic renal cell carcinoma (mRCC) has been found to differ in Western and Eastern populations. Here, we analyzed the efficacy and side effects of pazopanib as first-line therapy in 31 consecutive patients with mRCC who were treated at a single Chinese center. Thirty-one consecutive patients with mRCC (20 males and 11 females, median age 59 years) were treated with pazopanib between October 2017 and July 2019. All patients had received a pathological diagnosis of RCC by prior radical nephrectomy or biopsy. All cases were treated with pazopanib (800 mg/day orally) as first-line therapy. Administration was continued until disease progression or unacceptable toxicities occurred. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety were evaluated. Twenty-nine patients were eligible for final analysis. At the median follow-up of 12.7 months, 34.5% (10/29) patients achieved a partial response (PR), 41.4% (12/29) patients had stable disease (SD), seven (24.1%) patients had disease progression (PD), and one patient had died. The ORR and DCR were 34.5% and 75.9%, respectively, and the median PFS was 10.1 months (95% confidence interval, 4.1-17.7 months). OS could not be determined. The most common side effects were fatigue (11 cases, 37.9%), hand-foot syndrome (10 cases, 34.5%), change of hair color (10 cases, 34.5%), elevated alanine transaminase (ALT)/aspartate transaminase (AST) (10 cases, 34.5%), hypertension (seven cases, 24.1%), neutropenia (three cases, 10.3%), anemia (three cases, 10.3%), thrombocytopenia (two cases, 6.9%), and diarrhea (one cases, 3.4%). Major (grade 3 or higher) adverse events included hand-foot syndrome (two cases, 6.9%) and thrombocytopenia (one case, 3.4%). Most adverse events were ameliorated by dose reduction or treatment interruption. Remissions occurred in almost all patients with local recurrence or pulmonary metastases, whereas PD occurred in patients with bone, liver or brain metastases. Our real-world data suggest that pazopanib is definitely efficacious as first-line therapy for mRCC, with well-tolerated side effects. Different metastatic lesions may have different sensitivity to pazopanib. An additional, large sample, multicenter, prospective study is needed to confirm our results.

Clinical Outcomes after Selective Fetal Reduction of Complicated Monochorionic Twins with Radiofrequency Ablation and Bipolar Cord Coagulation.

AIMS: To review pregnancy outcomes, complication rates and neonatal neural development of selective termination procedures for complicated monochorionic (MC) twins. METHODS: This was a retrospective review of the pregnancies that underwent selective reduction with radiofrequency ablation (RFA) and bipolar cord coagulation (BCC) in our institution. RESULTS: Forty-eight cases underwent selective reduction with BCC and the remaining 45 with RFA. Overall survival was not statistically different between the RFA and BCC groups (71.1 and 62.5%, p = 0.379). With regard to the indications, the survival rates were not significantly different for twin to twin transfusion syndrome, twin reversed arterial perfusion, discordant anomalies and selective intrauterine growth restriction. Preterm premature rupture of membrane was not statistically different between the BCC and RFA groups (47.9 and 33.3%, p = 0.153). Five foetuses presented with abnormal middle cerebral artery-peak systolic velocity in the BCC group and 4 in the RFA group (p = 0.829). In the BCC group, neurological injury was detected in 2 neonates, presenting with cerebral dysplasia on MR scanning. In the RFA group, intracranial haemorrhage Grade III was detected in one neonate with cranial ultrasound (p = 0.607). CONCLUSIONS: Overall survival and complication rates following selective reduction in complicated MC twin pregnancies is similar irrespective of whether the reduction was performed using RFA or BCC. Key Message: It seems that selective reduction in MC pregnancies with RFA does not carry a significant decrease in the overall survival and complication rates than the cases with BCC. According to our data, neurodevelopmental impairment of the co-twins is relatively seldom after selective reduction.

Bisphenol A stimulates human lung cancer cell migration via upregulation of matrix metalloproteinases by GPER/EGFR/ERK1/2 signal pathway.

Lung cancer is one of the leading causes of cancer deaths worldwide. Recent evidences indicated that bisphenol A (BPA), a wide contaminant with endocrine disrupting activity, could enhance the susceptibility of carcinogenesis. Although there are increasing opportunities for lung cells exposure to BPA via inhalation, there is no study concerning the effects of BPA on the development of lung cancer. The present study revealed that BPA less than 10(-4)M had limited effects on the proliferation of lung cancer A549 cells, however, BPA treatment significantly stimulated the in vitro migration and invasion of cells combing with the morphological changes and up regulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. G-protein-coupled estrogen receptor (GPER), while not estrogen receptor α/ß (ERα/ß), mediated the BPA induced up regulation of MMPs. Further, BPA treatment induced rapid activation of ERK1/2 via GPER/EGFR. GPER/ERFR/ERK1/2 mediated the BPA induced upregulation of MMPs and in vitro migration of lung cancer A549 cells. In summary, our data presented here revealed for the first time that BPA can promote the in vitro migration and invasion of lung cancer cells via upregulation of MMPs and GPER/EGFR/ERK1/2 signals, which mediated these effects. This study suggested that more attention should be paid on the BPA and other possible environmental estrogens induced development of lung cancer.

Construction of pendant-armed Schiff-base macrocyclic dinuclear zinc complexes and their selective recognition of acetate ions.

Two new flexible extended dialdehydes (H2hpdd and H2pdd) with different functional pendant arms (-CH2CH2PhOH and -CH2CH2Ph) have been synthesized and reacted with 1,2-bis(2-aminoethoxy)ethane to prepare Schiff-base macrocyclic complexes in the presence of a Zn(II)-ion template. As a result, two preorganized dinuclear Zn(II) intermediates (1 and 2), as well as two 42-membered folded [2+2] macrocyclic dinuclear Zn(II) complexes (3 and 4), were produced. The central zinc ions in compounds 1-4 showed distinguishable coordination patterns with the dialdehydes and the [2+2] macrocyclic ligands, in which a subtle pH-adjustment function of the two pendant arms (with or without the phenolic hydroxy group) was believed to play a vital role. Furthermore, cation- and anion-recognition experiments for complexes 3 and 4 revealed that they could selectively recognize acetate ions by the formation of 1:1 stoichiometric complexes, as verified by changes in their UV/Vis and MS (ESI) spectra and even by the naked eye.

Zinc halide template effects on the construction of [1 + 1] flexible Schiff-base macrocyclic complexes having pendant-armed dialdehyde components.

Two novel pendant-armed dialdehydes (1a and 1b) were prepared by a one-step reaction between 5-chloro-3-(chloromethyl)-2-hydroxybenzaldehyde/5-methyl-3-(chloromethyl)-2-hydroxybenzaldehyde and cyclohexylamine involving two nucleophilic substitutions, and they were used to react with 1,3-propanediamine to prepare Schiff-base macrocyclic complexes in the presence of ZnX2 salts (X = Cl, Br, and I). As a result, five dinuclear (2a, 2b, 3b, 4a, and 4b) and one mononuclear (3a) [1 + 1] flexible macrocyclic Zn(II) complexes have been structurally and spectrally characterized. The zinc centers in three pairs of macrocyclic complexes have the common four-coordinate tetrahedral geometry with one or two coordinated halide ions, where the template Zn(II) cations and the auxiliary halide anions with different sizes and coordination abilities are believed to play important roles in forming the resulting macrocyclic complexes. In addition, subtle alterations of electron-withdrawing and electron-donating substituted groups (Cl versus CH3) in the macrocyclic backbone result in different (1)H NMR and UV-vis spectra.

Expression and functional validation of Bombyx mori nucleopolyhedrovirus ORF29, a conserved Nudix motif protein.

Our previous study showed that Bombyx mori nucleopolyhedrovirus (BmNPV) orf29 encodes a 26 kDa protein expressed in the early stage of infection cycle. BmNPV ORF29, contains a conserved motif of Nudix (nucleotide diphosphate X) superfamily. It has the highest homology with ADP-ribose pyrophosphatase (ADPRase), a subfamily of Nudix pyrophosphatase. In this work, we purified the recombinant BmNPV ORF29 in Escherichia coli by metal chelating affinity chromatography. The amino acid sequence of recombinant protein was confirmed by mass spectroscopic analysis and found that the purified protein could be able to catalyze the breakdown of ADP-ribose to AMP and ribose 5-phosphate, with Km and Kcat values of 182 µmol/l and 5.3 s-1 respectively. The optimal activity was at alkaline pH (8.5) with Mg2+ (0.5-mmol/l) ions as the cofactor.

Comparative proteome analysis of silkworm in its susceptibility and resistance responses to Bombyx mori densonucleosis virus.

Bombyx mori densonucleosis virus (BmDNV) is one of the most disastrous viruses in cocoon production. Silkworm resistance to BmDNV has been examined previously using a number of traditional biochemical and molecular techniques. In this study, a near isogenic line, BC(6), was constructed to eliminate the difference in inherited background, which has 99.9% identity with the susceptible strain but carries a resistant gene. We utilized a proteomic approach involving two-dimensional differential gel electrophoresis and mass spectrometry to examine changes in the midgut proteins from the susceptible and resistant silkworm larvae infected with BmDNV. The protein profiles were compared and 9 differentially expressed proteins were identified by mass spectrometry. In the resistant strains, the heat-shock 70-kDa protein cognate, cytochrome P450, vacuolar ATP synthase subunit B, arginine kinase, vacuolar ATP synthase subunit D and glutathione S-transferase sigma were strongly upregulated and α-tubulin was downregulated. Our results imply that these upregulated genes and the downregulated genes might be involved in B. mori immune responses against BmDNV-Z infection.

Characterization of a late gene, ORF67 from Bombyx mori nucleopolyhedrovirus.

Open reading frame 67 of Bombyx mori nucleopolyhedrovirus (BmORF67) is a homologue of Autographa californica multiple NPV ORF81. The gene is conserved among all baculoviruses and is thus considered a baculovirus core gene. The transcript of BmORF67 was detected at 18-72 h post-infection (p.i.). Polyclonal antiserum raised to a His-BmORF67 fusion protein recognized BmORF67 in infected cell lysates from 24 to 72 h p.i., suggesting that BmORF67 is a late gene. BmORF67 was not detected either in budded viruses or occlusion-derived virus. Immunofluoresence analysis showed that the protein located in the cytoplasm and interacted with host protein actin A3. In conclusion, BmORF67 is a late protein localized in the cytoplasm of infected cells that interacts with host protein.

[The diagnosis and monitoring of transitional cell cancer of the urinary tract through nuclear matrix protein 22].

OBJECTIVE: To evaluate the urinary nuclear matrix protein (NMP22) as an adjuvant diagnostic index for transitional cell carcinoma of urinary tract and monitoring the state of disease. METHODS: Urinary samples were collected from 262 patients with transitional cell carcinoma, 198 non-transitional cell carcinoma of the urinary tract and 65 patients with benign diseases. Urinary NMP22 concentration was determined through enzyme linked immunosorbent assay (ELISA). RESULTS: The urinary NMP22 concentration had significant difference among the three groups (Kruskal Wallis, chi(2) = 197.17 P < 0.001). The detection sensitivity and specificity of urinary NMP22 to transitional cell carcinoma were 71.37% and 87.69% respectively. The NMP22 concentration showed significant difference among three groups divided according to the pathological grade (Kruskal-Wallis test, chi(2) = 34.06 P < 0.01). The NMP22 concentration was significant lower in the recovery patients after the operation than the peoples of pre-operation and recurrence (Kruskal-Wallis test, chi(2) = 37.53, P < 0.001). CONCLUSION: MP22 is a helpful tumor marker for the diagnosis of transitional cell carcinoma and monitoring the state of illness with increased efficacy.

[Effects of NKG2D and its ligands RAE-1 and H60 on graft-versus-tumor response].

The study was purposed to explore the effects of NKG2D receptor and its ligands RAE-1 and H60 on graft-versus-tumor (GVT) response induced by MHC haploidentical bone marrow/spleen cell transplantation. Female (BALB/c x C57BL/6) F1 mice (CB6F1, H-2K(b/d)) inoculated with H22 cells to develop a solid tumor model were the recipients, and bone marrow mixed with spleen cells of the healthy male C57BL/6 (H-2K(b)) mice were the donor cells. GVT response was observed after transplantation that from donor cells T and NK cells were purged with anti-CD3 and anti-NK monoclonal antibody, and the NKG2D receptor was blocked with anti-NKG2D monoclonal antibody, the expression levels of RAE-1 and H60 mRNA in tumor tissue were measured by means of semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) at different time points after transplantation. The results showed that the GVT response of transplantation was reduced after in vitro depletion of T and NK cells or blocking NKG2D receptor in donor cells of the graft, the expression levels of RAE-1 and H60 mRNA in tumor tissue increased after transplantation of haploidential bone marrow mixed with spleen cells. It is concluded that NKG2D and its ligands RAE-1 and H60 may play important roles in GVT response.

Cloning and characterization of Bombyx mori PP-BP a gene induced by viral infection.

The ENF peptide family, so termed after the consensus sequence in their amino termini (Glu-Asn-Phe-), is assumed to play multiple important roles in defense reactions, growth regulation, and homeostasis of Lepidopteran insects. The paralytic peptide of Bombyx mori (BmPP) is one such peptide that is involved in the paralytic and plasmatocyte-spreading activities in the hemocyte immune reaction. The growth-blocking peptide of Pseudaletia separata (PsGBP), which is also a member of the ENF peptide family, has similar functions that can reportedly be attenuated by the growth-blocking peptide-binding protein (GBP-BP). Using the fluorescent differential display (FDD) technique, the differential expression pattern of genes in highly susceptible silkworm strain 306 were analyzed, following infection with B. mori nuclear polyhedrosis virus (BmNPV), and a differential band (G12(782)) was obtained from the hemolymph RNA pools. Using 5'-RACE with a specially designed primer based on the FDD study, a 1,401 bp cDNA clone was obtained containing a 1,311 bp open reading frame (ORF, GenBank accession number DQ306881). The deduced protein was highly homologous in primary structure to GBP-BP and was termed B. mori paralytic peptide-binding protein (PP-BP). The B. mori PP-BP gene is organized into two exons and only one intron, using bioinformatics searches.Using RT-PCR analysis, it was found that the B. mori PP-BP gene was expressed almost exclusively in the hemolymph. Real-time quantitative PCR analysis indicated that the B. mori PP-BP mRNA level in B. mori strain 306 exposed to BmNPV was much higher than that in B. mori strain without the virus infection. This result implies that the B. mori PP-BP is related to the cellular immune response after BmNPV invades the hemolymph.