Three 2,3-diketoquinoxaline alkaloids with hepatoprotective activity from Heterosmilax yunnanensis / 药学学报

Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors / 药学学报

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

Benzyl isothiocyanate induces cell cycle arrest and apoptosis in cervical cancer through activation of p53 and AMPK-FOXO1a signaling pathways / 中国药理学通报

Aim To investigate the effect of benzyl iso-thiocyanate (BITC) on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis. Methods The effect of BITC on U14 cell activity was detected by MTT, nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope, cell cycle and apoptosis were determined by flow cytometry, and the transcriptome database of U14 cells before and after BITC (20 μmol · L

The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Advances in clinical application of mass spectrometry for protein analysis / 中华检验医学杂志

In recent years, mass spectrometry-based protein analysis has emerged as a powerful tool in clinical laboratories, offering more reliable assessments than conventional laboratory tools and providing benefits for disease diagnosis and treatment. The use of targeted protein quantitation has gained widespread acceptance, particularly in the detection of insulin-like growth factor I, thyroglobulin, and monoclonal antibody therapeutics. Meanwhile, significant advancements have been made in non-targeted protein analysis, such as the diagnosis of amyloidosis, monoclonal gammopathies, and membranous nephropathy. High-resolution mass spectrometry has enabled the identification and differentiation of pathogenic proteins in these diseases, as well as the discovery of new proteins involved in disease onset and progression. As a result, clinical diagnosis and disease differentiation have improved, as well as our understanding of these diseases.

Progress in evaluating the risk of lymph node metastasis in early colorectal cancer / 中华胃肠外科杂志

Early colorectal cancers refer to invasive cancers that have infiltrated into the submucosa without invading muscularis propria, and approximately 10% of these patients have lymph node metastases that cannot be detected by conventional imaging. According to the guidelines of Chinese Society of Clinical Oncology (CSCO) Colorectal Cancer, early colorectal cancer cases with risk factors for lymph node metastasis (poor tumor differentiation, lymphovascular invasion, deep submucosal invasion and high-grade tumor budding) should receive salvage radical surgical resection; however, the specificity of this risk-stratification is inadequate, making most patients undergo unnecessary surgery. Firstly, this review focuses on the definition, oncological impact importance and controversy of the above "risk factors". Then, we introduce the progress of the risk stratification system for lymph node metastasis in early colorectal cancer, including the identification of new pathological risk factors, the construction of new risk quantitative models based on pathological risk factors, artificial intelligence and machine learning technology and the discovery of novel molecular markers associated with lymph node metastasis based on gene test or liquid biopsy. Aim to enhance clinicians' understanding of the risk assessment of lymph node metastasis in early colorectal cancer; we suggest to take the patient's personal situation, tumor location, anti-cancer intention and other factors into account to make individualized treatment strategies.

Correlation of anti-phosphatidylserine/prothrombin antibodies with unexplained recurrent miscarriages / 北京大学学报(医学版)

OBJECTIVE@#To investigate whether anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes were correlated with unexplained recurrent miscarriages.@*METHODS@#In our a single-center retrospective study, 283 patients with at least one unexplained miscarriage who visited the Third Hospital of Peking University between January 2021 and August 2023, aged between 18-40 years, and tested for anti-phosphatidylserine/prothrombin antibodies IgG or IgM subtypes, were included. The patients with either positive IgG or IgM anti-phosphatidylserine/prothrombin antibody were regarded as positive for anti-phosphatidylserine/prothrombin antibody. SPSS 26.0 software was used for statistical analysis. Chi-square test and Logistic regression analysis were used to study the correlation of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes with unexplained recurrent miscarriages. And the diagnostic sensitivity, specificity, the positive predictive value, the negative predictive value of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes in unexplained miscarriages was calculated with four-fold table.@*RESULTS@#Chi-square analysis showed that anti-phosphatidylserine/prothrombin antibodies and its IgM subtypes were correlated with recurrent miscarriages (both P < 0.05), while the IgG subtype was not correlated with recurrent miscarriages (P>0.05). After adjusting with anticardiolipin antibodies, anti-β2 glycoprotein antibodies, lupus anticoagulants, antinuclear antibodies, and age by Logistic regression analysis, anti-phosphatidylserine/prothrombin antibodies were correlated with unexplained recurrent miscarriages (OR=2.084, 95%CI 1.045-4.155, P < 0.05), and anti-phosphatidylserine/prothrombin antibody IgM subtypes were correlated with unexplained recurrent miscarriages (OR=2.368, 95%CI 1.187-4.722, P < 0.05).The sensitivity of anti-phosphatidylserine/prothrombin antibody in recurrent miscarriage was 65.43%, the specificity was 48.51%, the positive predictive value was 33.76%, and the negative predictive value was 77.78%. In the patients with recurrent miscarriages with negative classical antiphospholipid antibodies, the sensitivity of anti-phosphatidylserine/prothrombin antibody was 59.09%, the specificity was 63.23%, the positive predictive value was 40.63%, and the negative predictive value was 78.40%. The sensitivity of the anti-phosphatidylserine/prothrombin antibody IgM subtype for the diagnosis of recurrent miscarriage was 65.43%, the specificity was 50.99%, the positive predictive value was 34.87%, and the negative predictive value was 78.63%.@*CONCLUSION@#Anti-phosphatidylserine/prothrombin antibody and IgM subtype antibody are correlated with unexplained recurrent miscarriages in patients with at least one unexplained miscarriage. Whether positive anti-phosphatidylserine/prothrombin antibody or IgM subtype could predict future unexplained recurrent miscarriages warrants a prospective study.

Clinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients

INTRODUCTION@#Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity.@*METHOD@#Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases.@*RESULTS@#A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection.@*CONCLUSION@#This study demonstrates the benefit of early administration of the third dose among cancer patients.

The efficacy and side effects of rigosertib combined with chemotherapy in KRAS mutant colorectal cancer mice / 中华肿瘤杂志

Objective: To investigate the effect of rigosertib (RGS) combined with classic chemotherapy drugs including 5-fluorouracil, oxaliplatin, and irinotecan in colorectal cancer. Methods: Explore the synergy effects of RGS and 5-fluorouracil (5-FU), oxaliplatin (OXA), and irinotecan (IRI) on colorectal cancer by subcutaneously transplanted tumor models of mice. The mice were randomly divided into control group, RGS group, 5-FU group, OXA group, IRI group, 5-FU+ RGS group, OXA+ RGS group and IRI+ RGS group. The synergy effects of RGS and OXA on KRAS mutant colorectal cancer cell lines in vitro was detected by CCK-8. Ki-67 immunohistochemistry and TdT-mediated dUTP nick-end labeling (TUNEL) staining were performed on the mouse tumor tissue sections, and the extracted tumor tissue was analyzed by western blot. The blood samples of mice after chemotherapy and RGS treatment were collected, blood routine and liver and kidney function analysis were conducted, and H&E staining on liver sections was performed to observe the side effects of chemotherapy and RGS. Results: The subcutaneously transplanted tumor models were established successfully in all groups. 55 days after administration, the fold change of tumor size of OXA+ RGS group was 37.019±8.634, which is significantly smaller than 77.571±15.387 of RGS group (P=0.029) and 92.500±13.279 of OXA group (P=0.008). Immunohistochemical staining showed that the Ki-67 index of tumor tissue in control group, OXA group, RGS group and OXA+ RGS group were (100.0±16.8)%, (35.6±11.3)%, (54.5±18.1)% and (15.4±3.9)%, respectively. The Ki-67 index of OXA+ RGS group was significantly lower than that in control group (P=0.014), but there was no significant difference compared to OXA group and RGS group (OXA: P=0.549; RGS: P=0.218). TUNEL fluorescence staining showed that the apoptotic level of OXA+ RGS group was 3.878±0.547, which was significantly higher than 1.515±0.442 of OXA group (P=0.005) and 1.966±0.261 of RGS group (P=0.008). Western blot showed that the expressions of apoptosis related proteins such as cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 8 in the tumor tissues of mice in the OXA+ RGS group were higher than those in control group, OXA group and RGS group. After the mice received RGS combined with chemotherapy drugs, there was no significant effect on liver and kidney function indexes, but the combined use of oxaliplatin and RGS significantly reduced the white blood cells [(0.385±0.215)×10(9)/L vs (5.598±0.605)×10(9)/L, P<0.001] and hemoglobin[(56.000±24.000)g/L vs (153.333±2.231)g/L, P=0.001] of the mice. RGS, chemotherapy combined with RGS and chemotherapy alone did not significantly increase the damage to liver cells. Conclusions: The combination of RGS and oxaliplatin has a stronger anti-tumor effect on KRAS mutant colorectal cancer. RGS single agent will not cause significant bone marrow suppression and hepatorenal injury in mice, but its side effects may increase correspondingly after combined with chemotherapy.

Comparison of Thyroglobulin and Thyroid Function in Pregnant Women between Counties with a Median Urinary Iodine Concentration of 100-149 µg/L and 150-249 µg/L / 生物医学与环境科学（英文）

OBJECTIVE@#This study explored whether thyroglobulin and thyroid disease prevalence rates were higher in pregnant Chinese women with a median urinary iodine concentration of 100-149 µg/L, compared with those with a median urinary iodine concentration of 150-249 μg/L maintained through sustainable universal salt iodization.@*METHODS@#This was a cross-sectional study in which 812 healthy pregnant women were enrolled to collect samples of their household edible salt, urine, and blood during their routine antenatal care in the 18 counties in Fujian Province, China. The levels of salt iodine concentration, urinary iodine concentration (UIC), free triiodothyronine (FT3), free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroid peroxidase antibody and thyroglobulin antibody were assessed during the routine antenatal care visits.@*RESULTS@#The median UIC (mUIC) in pregnant women was 130.8 μg/L (interquartile range = 91.5-198.1 μg/L) in the counties with an mUIC of 100-149 μg/L (Group I), and 172.0 μg/L (interquartile range = 123.5-244.4 μg/L) in the counties with an mUIC of 150-249 μg/L (Group II). Goiter prevalence and thyroid nodule detection rates showed no difference between Group I and Group II ( P > 0.05). Except for FT4 values, the TSH, FT4, FT3, Tg and Tg values > 40 (μg/L) and the thyroid diseases prevalence rate (TDR) showed no significant differences between Group I and Group II ( P > 0.05), whether or not iodine supplementation measures were taken.@*CONCLUSION@#Compared with an mUIC of 150-249 μg/L, not only there was no difference in thyroid morphology, but also the Tg value, rate of Tg values > 40 µg/L, and TDR were not higher in pregnant women in the counties with an mUIC of 100-149 μg/L achieved through sustainable universal salt iodization in Fujian Province, China.

Isolation of Leclercia adecarboxylata Producing Carbapenemases in A Newborn Female / 生物医学与环境科学（英文）

Leclercia adecarboxylata is a Gram-negative bacterium belonging to the Enterobacteriaceae family. To our knowledge, this is the first report of a carbapenem-resistant L. adecarboxylata strain isolated from a healthy newborn. The L. adecarboxylata strain isolated in this study carried four plasmids that may serve as reservoirs for antibiotic resistance genes. Plasmids 2 and 4 did not harbor any antimicrobial resistance genes. Plasmid 3 is a novel plasmid containing three resistance genes. The bla IMP gene harbored in the strain was most similar to bla IMP-79 at the nucleotide level, with a similarity of 99.4% (737/741). This case highlights the importance of considering L. adecarboxylata as a potential cause of infections in children.

The role of mitochondria-associated endoplasmic reticulum membranes in age-related cardiovascular diseases / 生理学报

Mitochondria-associated endoplasmic reticulum membranes (MAMs) are the physical connection sites between mitochondria and endoplasmic reticulum (ER). As the compartments controlling substance and information communications between ER and mitochondria, MAMs were involved in the regulation of various pathophysiological processes, such as calcium homeostasis, mitochondrial morphology and function, lipid metabolism and autophagy. In the past decades, accumulating lines of evidence have revealed the pivotal role of MAMs in diverse cardiovascular diseases (CVD). Aging is one of the major independent risk factors for CVD, which causes progressive degeneration of the cardiovascular system, leading to increased morbidity and mortality of CVD. This review aims to summarize the research progress of MAMs in age-related CVD, and explore new targets for its prevention and treatment.

Three new anthraquinones from Prismatomeris tetrandra (Roxb.) K. Schum and their protective effects in neuroblastoma cells / 药学学报

Three new anthraquinones were isolated from the 80% ethanol extract of Prismatomeris tetrandra by silica gel, MCI, ODS column chromatography and high performance preparative liquid chromatography (HPLC). The structures of the new compounds were identified by mass spectrometry, nuclear magnetic resonance and other spectroscopic methods as 6-hydroxy-1,2,3-trimethoxy-7-methylanthracene-9,10-dione (1), 6-(hydroxymethyl)-1,2,3-trimethoxyanthracene-9,10-dione (2) and 7-hydroxy-6-(hydroxymethyl)-1,2-dimethoxyanthracene-9,10-dione (3). Compounds 1, 2 and 3 showed protective effects against monosodium glutamate-induced damage in SH-SY5Y neuroblastoma cells, with the cell survival rates elevated 18.45%, 4.31%, and 7.65%, respectively.

Mapping out the surgical anatomy of the lingual nerve:a systematic review and meta-analysis

Objectives@#Understanding the lingual nerve’s precise location is crucial to prevent iatrogenic injury. This systematic review seeks to determine the lingual nerve’s most probable topographical location in the posterior mandible. @*Materials and Methods@#Two electronic databases were searched, identifying studies reporting the lingual nerve’s position in the posterior mandible.Anatomical data in the vertical and horizontal dimensions at the retromolar and molar regions were collected for meta-analyses. @*Results@#Of the 2,700 unique records identified, 18 studies were included in this review. In the vertical plane, 8.8% (95% confidence interval [CI], 1.0%-21.7%) and 6.3% (95% CI, 1.9%-12.5%) of the lingual nerves coursed above the alveolar crest at the retromolar and third molar regions. The mean vertical distance between the nerve and the alveolar crest ranged from 12.10 to 4.32 mm at the first to third molar regions. In the horizontal plane, 19.9% (95% CI, 0.0%-62.7%) and 35.2% (95% CI, 13.0%-61.1%) of the lingual nerves were in contact with the lingual plate at the retromolar and third molar regions. @*Conclusion@#This systematic review mapped out the anatomical location of the lingual nerve in the posterior mandible, highlighting regions that warrant additional caution during surgeries to avoid iatrogenic lingual nerve injuries.

Effects of overexpression of IncRNA AC079466.1 on apoptosis of NSCLC cells through endoplasmic reticulum stress signaling pathway / 中国药理学通报

Aim To investigate the expression of IncRNA AC079466. 1 in non-small cell lung cancer (NSCLC) tissues and cells, and the effect of its overexpression on the proliferation, apoptosis, migration and invasion of A549 and H1299 cells. Methods Cancer tissues and corresponding adjacent tissues from 20 NSCLC patients were collected, and the expression of IncRNA AC079466. 1 in tissue and cells was detected by qRT-PCR. AC079466. 1 group was transfected with overexpression plasmid, NC group was transfected with empty plasmid, and no transfection was used in the Blank group. MTT, flow cytometry and Transwell were used to detect the effects of IncRNA AC079466. 1 overexpression on the viability, apoptosis, migration and invasion of A549 and HI299 cells. Western blot was used to detect the effect of overexpression of IncRNA AC079466. 1 on the expression of endoplasmic reticulum stress-related factors GRP78, PERK, eIF2a, ATF4, CHOP, Bax and caspase-3. Results Compared with adjacent tissues, the expression of IncRNA AC079466. 1 in cancer tissues significantly decreased. Compared with HBE cells, the expression of IncRNA AC079466. 1 significantly decreased in A549 and H1299 cells. Compared with the Blank group and NC group, the viability, migration and invasion abilities of A549 and H1299 cells in AC079466. 1 group all markedly decreased, the apoptosis rate apparently increased, and the expressions of endoplasmic reticulum stress-related factors GRP78, p-PERK, eIF2a, ATF4, CHOP, Bax and caspase-3 were significantly up-regulated. Conclusion The overexpression of IncRNA AC079466. 1 significantly inhibits the viability, migration and invasion of A549 and HI299 cells, and promotes cell apoptosis. The mechanism may be related to the promotion of endoplasmic reticulum stress-mediated cell apoptosis.

Regulation of Yes associated protein in diabetic nephropathy mice by Yishen Huashi Granule / 中国药理学通报

Aim To explore the protective effect of Yishen Huashi Granule (YSHS) on streptozotocin (STZ) - indueed diabetes nephropathy (DN) in mice and its possible mechanism. Methods The STZ induced DN mice model was established, which was randomly divided into model group, YSHS group and YAP inhibitor Vertepofin group, and the eontrol group was also established. The intervention was started eight weeks after the successful modeling with the course of four weeks. Urine protein concentration before and after intervention in each group as well as serum creatinine (Scr) and blood urea nitrogen (Bun) levels after intervention were measured. After the treatment, the mice were sacrificed, and the pathological changes of glomeruli were observed by light microscope HE staining. The protein expression of YAP, p-YAP S127 and CTGF were detected by Western blot, and the mRNA expressions of YAP, CTGF and podocyte functional proteins nephrin, podophyxin and WT1 were detected by RT-PCR. Results The biochemical indexes of YSHS group were better than those of model group, and HE staining showed that the pathological injury of glomeruli was improved. In the model group the protein expression of YAP, p-YAP (S127) and CTGF as well as the mRNA expression of YAP and CTGF increased, while the mRNA expression of nephrin, podocalyxin and WT1 decreased. After YSHS treatment, the protein expression of YAP, p-YAP S127, CTGF and the mRNA expression of YAP and CTGF decreased, while the mRNA expression of nephrin, podocalyxin and WT1 increased. Conclusions YSHS can reduce urinary protein, protect renal function and alleviate glomerular pathological injury in DN mice. Its possible mechanism may be related to the down-regulation of YAP in renal tissue, the reduction of CTGF expression level and the up-regulation of podocyte protein mRNA expression.

Construction of interferon alpha/beta receptor subunit 1 gene knockout Caco-2 cell line based on CRISPR/Cas9 system / 中国生物制品学杂志

@#Objective To knockout interferon alpha/beta receptor subunit 1(IFNAR1) gene in human colorectal adenocarcinoma cells Caco-2 using clustered regularly interspaced short palinmic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system to construct IFNAR1 knockout Caco-2 cell line.Methods The single guide RNA(sgRNA)sequence was designed to specifically recognize the exon region of IFNAR1 gene using CRISPR/Cas9 technology,and the LentiCRISPRv2-IFNAR1-sgRNA recombinant plasmid was constructed.Caco-2 cells were infected with the plasmid packaged by lentivirus and screened by puromycin resistance.The obtained monoclonal cell lines were cultured by limited dilution method,which were verified for the effect of IFNAR1 gene knockout by target gene sequencing and Western blot,and detected for the mRNA levels of CXC chemokine ligand 10(CXCL10)and interferon-stimulatd gene 20(ISG20)in IFNAR1knockout cells by adding exogenous IFNβ.Results Sequencing results of plasmid LentiCRISPRv2-IFNAR1-sgRNA showed that the insertion sites were all located at the sticky end of BsmBⅠenzyme digestion.Two IFNAR1 knockout monoclonal cell lines were obtained.The sequencing results showed that Caco-2-IFNAR1-KO1 had 5 bp deletion in the sixth exon of IFNAR1,and Caco-2-IFNAR1-KO2 had 18 bp deletion and 1 bp insertion in the seventh exon.Compared with wild-type Caco-2 cells,Caco-2-IFNAR1-KO1 and Caco-2-IFNAR1-KO2 cells showed no expression of IFNAR1 protein.Compared with no IFNβ stimulation,the mRNA levels of CXCL10 gene(t = 0.566 and 1.268 respectively,P>0.05)and ISG20 gene(t =1.522 and 1.733 respectively,P>0.05)in Caco-2-IFNAR1-KO1 and Caco-2-IFNAR1-KO2 cells stimulated by 50 ng/mL IFNβ showed no significant increase.While compared with those of wild-type Caco-2 cells,the mRNA levels of CXCL10gene(t = 6.763 and 6.777 respectively,P<0.05)and ISG20 gene(t = 5.664 and 5.65 respectively,P<0.05)in Caco-2-IFNAR1-KO1 and Caco-2-IFNAR1-KO2 cells decreased significantly under the stimulation of 50 ng/mL exogenous IFNβ.Conclusion Caco-2 cell line with IFNAR1 knockout was successfully constructed by using CRISPR/Cas9 technology,and the downstream molecules activated by IFNAR(interferon alpha/beta receptor)in this cell line were obviously inhibited,which provided a powerful tool for further exploration of the innate immune response and replication packaging mechanism of Caco-2 cells after virus infection.

Connexin 43: A new therapeutic target against blinding eye diseases / 国际眼科杂志(Guoji Yanke Zazhi)

The major blinding eye diseases, such as keratitis, cataract, glaucoma, diabetic retinopathy, seriously threaten human health and affect the quality of patients' life. Connexin 43(Cx43), as the most common connexin in vertebrates, is widely distributed in eye tissues and is involved in physiological processes such as embryonic development, metabolic regulation, tissue homeostasis, as well as pathological processes such as inflammation, oxidative stress, epithelial-mesenchymal transition, vascular leakage, and angiogenesis. Cx43 plays an important role in the occurrence and development of various blinding eye diseases. This article will review its role in the pathogenesis of the above-mentioned blinding eye diseases and the advances in targeting Cx43 therapy.

Mental Health Status and Influencing Factors of Pediatricians in Guangzhou / 中山大学学报(医学科学版)

ObjectiveTo investigate the mental health of pediatricians in Guangzhou and its influencing factors， and to provide countermeasures for improving the mental health of pediatricians. MethodsA stratified random sampling method was used to randomly select 400 pediatricians in 11 districts of Guangzhou， and they were surveyed using the Symptom Check List（SCL-90） and the Job Stressor Scale. ResultsThe top three job stressors scored by pediatricians in Guangzhou were external environment （3.23±0.59）， workload （3.19±0.56）， and organizational management （2.74±0.55）. All factor scores were higher than those of the clinician group except for career interest， and the difference was statistically significant （P<0.01）. The number of pediatricians with mental health problems was 109， accounting for 27.25%. All factor scores were higher than the physician norm except for anxiety and paranoia. The correlations between each factor of work stressors and each factor of SCL-90 were positive and statistically significant （P<0.05）， except for two pairs of factors， workload and terror as well as external environment and terror. The results of univariate analysis showed statistically significant differences in the mental health scores of pediatricians with different health status， years of work experience， job satisfaction， job stress， and career prospects （P<0.05）. The results of multiple linear regression showed that health status， years of work experience， professional interest， interpersonal relationship， and doctor-patient relationship were influential factors in the mental health of pediatricians （P<0.05）. ConclusionThe mental health of pediatricians in Guangzhou is unsatisfactory， and the factors affecting them are mainly external objective factors such as workload and organizational management.

Medication rules of traditional Chinese medicine compounds for pain / 中国中药杂志

The present study collected data on traditional Chinese medicine(TCM) compounds effective in relieving pain from the patent database of the State Intellectual Property Office(SIPO), sorted out the TCM compounds against pain in patents, and analyzed the medication rules to provide references for the research and development of new TCM drugs against pain. The data were subjected to frequency statistics, association rules, cluster analysis, and complex network analysis by IBM SPSS Modeler 18.3 and SPSS Statistical 26.0. The results showed that among the 101 oral prescriptions included in the statistics, the top 5 drugs were Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, Chuanxiong Rhizoma, and Salviae Miltiorrhizae Radix et Rhizoma, and among the 49 external prescriptions included in the statistics, the top 5 drugs were Myrrha, Olibanum, Angelicae Dahuricae Radix, Borneolum Syntheticum, and Chuanxiong Rhizoma. Whether oral or external prescriptions, the drugs were mainly warm in nature, and bitter, pungent, and sweet in flavor. According to TCM complex network analysis, the core drugs were Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, and Chuanxiong Rhizoma in oral prescriptions, and Olibanum, Myrrha, Glycyrrhizae Radix et Rhizoma, Chuanxiong Rhizoma, and Angelicae Sinensis Radix in external prescriptions. Overall, the therapeutic principles of oral prescriptions were mainly replenishing Qi, nourishing blood, and promoting Qi and blood circulation, while those of external prescriptions were activating blood, resolving stasis, promoting Qi flow, and relieving pain on the basis of the oral prescriptions. In the future research and development of TCM compounds against pain, the prescriptions should be modified with mind-tranquilizing and depression-relieving drugs. With the modernization of TCM, the development of new pain-relieving TCM compound patents based on ancient methods and clinical experience adhering to the guidance of TCM treatment based on syndrome differentiation can meet the new demand for pain treatment in the current society and give full play to the advantages of TCM in pain treatment.