RN486, a Bruton's Tyrosine Kinase inhibitor, antagonizes multidrug resistance in ABCG2-overexpressing cancer cells.

Background and Objectives: Overcoming ATP-binding cassette subfamily G member 2 (ABCG2)-mediated multidrug resistance (MDR) has attracted the attention of scientists because one of the critical factors resulting in MDR in cancer is the overexpression of ABCG2. RN486, a Bruton's Tyrosine Kinase (BTK) inhibitor, was discovered to potentially reverse ABCB1-mediated MDR. However, there is still uncertainty about whether RN486 has a reversal off-target impact on ABCG2-mediated MDR. Methods: MTT assay was used to detect the reversal effect of RN486 on ABCG2-overexpressing cancer cells. The ABCG2 expression level and subcellular localization were examined by Western blotting and immunofluorescence. Drug accumulation and eflux assay and ATPase assay were performed to analyze the ABCG2 transporter function and ATPase activity. Molecular modeling predicted the binding between RN486 and ABCG2 protein. Results: Non-toxic concentrations of RN486 remarkably increased the sensitivity of ABCG2-overexpressing cancer cells to conventional anticancer drugs mitoxantrone and topotecan. The reversal mechanistic studies showed that RN486 elevated the drug accumulation because of reducing the eflux of ABCG2 substrate drug in ABCG2-overexpressing cancer cells. In addition, the inhibitory efect of RN486 on ABCG2-associated ATPase activity was also verified. Molecular docking study implied a strong binding afinity between RN486 and ABCG2 transporter. Meanwhile, the ABCG2 subcellular localization was not altered by the treatment of RN486, but the expression level of ABCG2 was down-regulated. Conclusions: Our studies propose that RN486 can antagonize ABCG2-mediated MDR in cancer cells via down-regulating the expression level of ABCG2 protein, reducing ATPase activity of ABCG2 transporter, and inhibiting the transporting function. RN486 could be potentially used in conjunction with chemotherapy to alleviate MDR mediated by ABCG2 in cancer.

Analysis of short-term efficacy of one-stage posterior sparing laminectomy for single level thoracolumbar tuberculosis / 重庆医学

Objective To explore the feasibility and short-term clinical efficacy of single segment thora-columbar tuberculosis treated with one-stage posterior approach lamina-sparing decompression.Methods A total of 11 patients with single segment thoracolumbar tuberculosis who underwent one-stage posterior ap-proach preservation of vertebral plate lesion removal,bone graft fusion,and internal fixation treatment in this hospital from September 2021 to June 2022 were selected.C-reactive protein(CRP)and erythrocyte sedimen-tation rate(ESR)were monitored to evaluate tuberculosis bacteremia and activity control,visual analogue scale(VAS)score and Oswestry disability index(ODI)were followed up to evaluate the improvement of clin-ical function,and the American Spinal Injury Association(ASIA)injury scale was used to evaluate neurologi-cal function,and the correction of kyphosis was followed up.Results All 11 patients were fully followed up.The average surgical duration is(270.91±45.98)minutes,and the average surgical bleeding is(522.72± 194.11)mL.During the follow-up period,none of the 11 patients experienced tuberculosis recurrence,and all 11 patients achieved bone graft fusion.The fusion time was 6-9 months after surgery with an average of(7.36±1.12)months.Two patients with preoperative nerve damage recovered after surgery.During the fol-low-up period,11 patients did not experience any complications related to surgery.The average CRP,ESR,ODI score,and VAS score of postoperative patients decreased compared to preoperative levels,and further de-creased at 12 months after surgery;The patient's kyphosis caused by thoracolumbar tuberculosis was correc-ted,and no obvious angle loss was found at the last follow-up(P＞0.05).Conclusion One-stage posterior ap-proach lamina-sparing decompression is a safe and effective method for treating single segment thoracolumbar tuberculosis.

Advances on reprogramming of fatty acid metabolism in pulmonary fibrosis / 基础医学与临床

Pulmonary fibrosis is a progressive interstitial fibrotic lung disease with high mortality.Its pathogenesis is complex and involves the reprogramming of fatty acid metabolism.This reprogramming includes changes in de novo fatty acid synthesis,uptake,oxidation,and derivatives.It crucially influences alveolar epithelial cell survival,macrophage polarization,and fibroblast activation,thereby playing a significant role in either exacerbating or miti-gating the disease.Understanding and intervening in the reprogramming of fatty acid metabolism offers potential strategies for prevention,diagnosing and treatment of pulmonary fibrosis.

A virtual simulation system-based teaching method for the experimental course of oral local nerve block anesthesia / 中华医学教育探索杂志

Objective:To investigate the effect of the virtual simulation system-based teaching method for the experimental course of oral local nerve block anesthesia in improving the effect of traditional teaching methods.Methods:One hundred and eighteen undergraduate dental students were randomly divided into two groups, the experimental group was taught using a virtual simulation-based system, and the control group was taught using traditional teaching. The results of the teaching were comprehensively evaluated through course feedback questionnaires, analysis of theoretical test scores, evaluations of the trainees administering and receiving anesthesia on the current anesthesia, and faculty evaluations of the success of the anesthesia, and t-tests and chi-square tests were performed using SPSS 23.0.Results:There was no significant difference in baseline level between the two groups. The students in the experimental group thought that the learning was more vivid ( t=4.24, P=0.005) and had more self-confidence in local anesthesia ( t=4.99, P<0.001). The students in the experimental group felt less needle tip jitter during injection ( t=2.22, P=0.048) and better contact with the medial surface of the mandible ( t=2.22, P=0.020). The students who received anesthesia reported less pain during injection ( t=1.99, P=0.029) and better anesthesia of the inferior alveolar nerve ( t=3.36, P=0.039) in the experimental group. Teacher assessment revealed that the experimental group had a significantly lower failure rate of inferior alveolar nerve block than the control group ( χ2=4.40, P=0.036). Conclusions:The virtual simulation system can optimize the experimental teaching of oral local nerve block anesthesia and can achieve a satisfactory teaching effect.

HbBIN2 Functions in Plant Cold Stress Resistance through Modulation of HbICE1 Transcriptional Activity and ROS Homeostasis in Hevea brasiliensis.

Cold stress poses significant limitations on the growth, latex yield, and ecological distribution of rubber trees (Hevea brasiliensis). The GSK3-like kinase plays a significant role in helping plants adapt to different biotic and abiotic stresses. However, the functions of GSK3-like kinase BR-INSENSITIVE 2 (BIN2) in Hevea brasiliensis remain elusive. Here, we identified HbBIN2s of Hevea brasiliensis and deciphered their roles in cold stress resistance. The transcript levels of HbBIN2s are upregulated by cold stress. In addition, HbBIN2s are present in both the nucleus and cytoplasm and have the ability to interact with the INDUCER OF CBF EXPRESSION1(HbICE1) transcription factor, a central component in cold signaling. HbBIN2 overexpression in Arabidopsis displays decreased tolerance to chilling stress with a lower survival rate and proline content but a higher level of electrolyte leakage (EL) and malondialdehyde (MDA) than wild type under cold stress. Meanwhile, HbBIN2 transgenic Arabidopsis treated with cold stress exhibits a significant increase in the accumulation of reactive oxygen species (ROS) and a decrease in the activity of antioxidant enzymes. Further investigation reveals that HbBIN2 inhibits the transcriptional activity of HbICE1, thereby attenuating the expression of C-REPEAT BINDING FACTOR (HbCBF1). Consistent with this, overexpression of HbBIN2 represses the expression of CBF pathway cold-regulated genes under cold stress. In conclusion, our findings indicate that HbBIN2 functions as a suppressor of cold stress resistance by modulating HbICE1 transcriptional activity and ROS homeostasis.

A Chinese Herb Prescription "Fang-gan Decoction" Protects Against Damage to Lung and Colon Epithelial Cells Caused by the SARS-CoV-2 Spike Protein by Regulating the TGF-ß/Smad2/3 and NF-κB Pathways.

Objective To explore the effects and mechanisms of a traditional Chinese medicine (TCM) prescription, "Fang-gan Decoction" (FGD), in protecting against SARS-CoV-2 spike protein-induced lung and intestinal injuries in vitro and in vivo.Methods Female BALB/c mice and three cell lines pretreated with FGD were stimulated with recombinant SARS-CoV-2 spike protein (spike protein). Hematoxylin-eosin (HE) staining and pathologic scoring of tissues, cell permeability and viability, and angiotensin-converting enzyme 2 (ACE2) expression in the lung and colon were detected. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of inflammatory factors in serum and cell supernatant. The expression of NF-κB p65, p-NF-κB p65, p-IκBα, p-Smad2/3, TGF-ß1, Caspase3, and Bcl-2 was evaluated by Western blotting.Results FGD protected against the damage to the lung and colon caused by the spike protein in vivo and in vitro according to the pathologic score and cell permeability and viability (P<0.05). FGD up-regulated ACE2 expression, which was reduced by the spike protein in the lung and colon, significantly improved the deregulation of inflammatory markers caused by the spike protein, and regulated the activity of TGF-ß/Smads and NF-κB signaling.Conclusion Traditional Chinese medicine has a protective effect on lung and intestinal tissue injury stimulated by the spike protein through possible regulatory functions of the NF-κB and TGF-ß1/Smad pathways with tissue type specificity.

N,N-dimethylacetamide targets neuroinflammation in Alzheimer's disease in in-vitro and ex-vivo models.

Alzheimer's disease (AD) is a chronic degenerative brain disorder with no clear pathogenesis or effective cure, accounting for 60-80% of cases of dementia. In recent years, the importance of neuroinflammation in the pathogenesis of AD and other neurodegenerative disorders has come into focus. Previously, we made the serendipitous discovery that the widely used drug excipient N,N-dimethylacetamide (DMA) attenuates endotoxin-induced inflammatory responses in vivo. In the current work, we investigate the effect of DMA on neuroinflammation and its mechanism of action in in-vitro and ex-vivo models of AD. We show that DMA significantly suppresses the production of inflammatory mediators, such as reactive oxygen species (ROS), nitric oxide (NO) and various cytokines and chemokines, as well as amyloid-ß (Aß), in cultured microglia and organotypic hippocampal slices induced by lipopolysaccharide (LPS). We also demonstrate that DMA inhibits Aß-induced inflammation. Finally, we show that the mechanism of DMA's effect on neuroinflammation is inhibition of the nuclear factor kappa-B (NF-κB) signaling pathway and we show how DMA dismantles the positive feedback loop between NF-κB and Aß synthesis. Taken together, our findings suggest that DMA, a generally regarded as safe compound that crosses the blood brain barrier, should be further investigated as a potential therapy for Alzheimer's disease and neuroinflammatory disorders.

Abnormal expression of miRNA-122 in cerebral infarction and related mechanism of regulating vascular endothelial cell proliferation and apoptosis by targeting CCNG1.

OBJECTIVE: To analyze the value of serum miRNA-122 expression in the diagnosis, severity, and prognosis of Acute Cerebral Infarction (ACI) and the correlation mechanism of serum miRNA-122 on the proliferation and apoptosis of vascular endothelial cells in ACI. METHOD: A total of 60 patients with ACI who were admitted to the emergency department of the Taizhou People's Hospital from January 1, 2019, to December 30, 2019, and 30 healthy controls during the same period were selected. General clinical data of all patients at admission were collected. Including age, sex, medical history, and inflammatory factors (C-Reactive Protein [CRP], Interleukin-6 [IL-6], Procalcitonin [PCT], Neutrophil Gelatinase-Associated Lipid carrier protein [NGAL]). The National Institutes of Health Stroke Scale (NIHSS) score at admission and short-term prognosis (the Modified Rankin Score [mRS]) score at 3 months after onset were recorded. The expression level of miRNA-122 in the serum of patients with ACI and normal controls was detected by reverse-transcription quantitative Real-Time Polymerase Chain Reaction (RT-QPCR), and the correlation between the expression level of miRNA-122 in the serum of patients with ACI and the level of inflammatory factors, NIHSS and mRS scores were analyzed. The expression levels of miRNA-122 in the serum of patients with ACI, normal people, and Human Umbilical cord Endothelial Cells (HUVECs) cultured in a blank control group were detected by RT-QPCR and statistically analyzed. MTT and flow cytometry was used to compare the proliferation and apoptosis of vascular endothelial cells in the miRNA-122 mimics and inhibitors transfection groups and the corresponding negative control group. The mRNA and protein levels of apoptosis-related factors Bax, Bcl-2, Caspase-3, and angiogenesis-related proteins Hes1, Notch1, Vascular Endothelial Growth Factors (VEGF), and CCNG1 were detected by RT-QPCR and Western blot. Bioinformatics methods predicted CCNG1 to be the target of miRNA-122, and the direct targeting relationship between CCNG1 and miRNA-122 was verified by a dual-luciferase reporting assay. RESULT: Serum miRNA-122 expression in patients with ACI was significantly higher than that in healthy controls, with an area under the receiver operating characteristic curve of 0.929, 95% Confidence Interval of 0.875‒0.983, and an optimal cut-off value of 1.397. The expression levels of CRP, IL-6, and NGAL in patients with ACI were higher than those in healthy control groups, p < 0.05; miRNA-122 was positively correlated with CPR, IL-6, NIHSS score, and mRS score. At 48h and 72h, the proliferation rate of HUVECs cells in the miRNA-122 mimics group decreased and the apoptosis rate increased. Cell proliferation rate increased, and apoptosis rate decreased significantly in the groups transfected with miRNA-122 inhibitors. The mRNA and protein levels of pro-apoptotic factors Bax and caspase-3 were significantly increased in the miRNA-122 mimics transfection group, while those of anti-apoptotic factor Bcl-2 were significantly decreased compared to those of the control group. The expression of Bax and Caspase-3 decreased, and the expression of anti-apoptotic factor Bcl-2 increased in the transfected miRNA-122 inhibitors group. mRNA expression levels of Hes1, Notch1, VEGF, and CCNG1 in the miRNA-122 mimic transfected group were significantly decreased, while mRNA expression levels in the miRNA-122 inhibitors transfected group were significantly increased. Bioinformatics showed that there was a miRNA-122 binding site in the 3'UTR region of CCNG1, and dual luciferase assay confirmed that CCNG1 was the target of miRNA-122. CONCLUSION: Serum miRNA-122 increased significantly after ACI, which may be a diagnostic marker of ACI. miRNA-122 may be involved in the pathological process of ACI and is related to the degree of neurological impairment and short-term prognosis in patients with ACI. miRNA-122 may play a regulatory role in ACI by inhibiting cell proliferation, increasing apoptosis, and inhibiting vascular endothelial cell regeneration through the CCNG1 channel.

Pneumonia risk prediction in patients with acute alcohol withdrawal syndrome through evaluation of sarcopenia index as a prognostic factor.

OBJECTIVE: This study aimed to explore the relationship between the sarcopenia index (SI) and the risk of pneumonia in hospitalized patients with acute alcohol withdrawal syndrome (AWS). STUDY DESIGN: We have performed a retrospective study of individuals with AWS from a teaching hospital in western China. Patients' data were retrieved from the medicinal record databases. Patients' primary (upon admission) blood serum creatinine (Cr) and cystatin C (CysC) levels were incorporated into the records. Participants were separated into low and high SI cohorts based on the three-quarter digit of SI (SI = serum Cr/serum CysC ratio × 100). The association between SI and the risk of pneumonia in hospitalized patients with AWS was assessed by logistic regression analysis. RESULT: Three hundred and twelve patients with acute AWS were included in this retrospective analysis. Among hospitalized patients with acute AWS, the incidence of pneumonia was 13.78%. The average median age of acute AWS patients with pneumonia was 55.28 (10.65) years, and the mean age of acute AWS individuals without pneumonia was 51.23 (10.08) years. In the univariate analysis, the high SI group (SI > 87.91) had a lower incidence of pneumonia than the low SI group (SI ≤ 87.91) (high SI vs. low SI, 6.41% vs. 16.24%, p = 0.029). Further logistic regression analysis showed that the high SI group demonstrated a poorer risk of pneumonia (OR = 0.353, 95%CI: 0.134-0.932, p = 0.036). After adjusting for possible confounders, the risk of pneumonia remained low in the high SI group (OR = 0.358, 95%CI: 0.132-0.968, p = 0.043). CONCLUSION: Our results showed that SI was linked with the risk of pneumonia in hospitalized individuals with acute AWS. We further suggest that it could be a pneumonia risk factor, especially in medical centers where sarcopenia diagnosis is unavailable.

Abnormal expression of miRNA-122 in cerebral infarction and related mechanism of regulating vascular endothelial cell proliferation and apoptosis by targeting CCNG1

Abstract Objective: To analyze the value of serum miRNA-122 expression in the diagnosis, severity, and prognosis of Acute Cerebral Infarction (ACI) and the correlation mechanism of serum miRNA-122 on the proliferation and apoptosis of vascular endothelial cells in ACI. Method: A total of 60 patients with ACI who were admitted to the emergency department of the Taizhou People's Hospital from January 1, 2019, to December 30, 2019, and 30 healthy controls during the same period were selected. General clinical data of all patients at admission were collected. Including age, sex, medical history, and inflammatory factors (C-Reactive Protein [CRP], Interleukin-6 [IL-6], Procalcitonin [PCT], Neutrophil Gelatinase-Associated Lipid carrier protein [NGAL]). The National Institutes of Health Stroke Scale (NIHSS) score at admission and short-term prognosis (the Modified Rankin Score [mRS]) score at 3 months after onset were recorded. The expression level of miRNA-122 in the serum of patients with ACI and normal controls was detected by reverse-transcription quantitative Real-Time Polymerase Chain Reaction (RT-QPCR), and the correlation between the expression level of miRNA-122 in the serum of patients with ACI and the level of inflammatory factors, NIHSS and mRS scores were analyzed. The expression levels of miRNA-122 in the serum of patients with ACI, normal people, and Human Umbilical cord Endothelial Cells (HUVECs) cultured in a blank control group were detected by RT-QPCR and statistically analyzed. MTT and flow cytometry was used to compare the proliferation and apoptosis of vascular endothelial cells in the miRNA-122 mimics and inhibitors transfection groups and the corresponding negative control group. The mRNA and protein levels of apoptosis-related factors Bax, Bcl-2, Caspase-3, and angiogenesis-related proteins Hes1, Notch1, Vascular Endothelial Growth Factors (VEGF), and CCNG1 were detected by RT-QPCR and Western blot. Bioinformatics methods predicted CCNG1 to be the target of miRNA-122, and the direct targeting relationship between CCNG1 and miRNA-122 was verified by a dual-luciferase reporting assay. Result: Serum miRNA-122 expression in patients with ACI was significantly higher than that in healthy controls, with an area under the receiver operating characteristic curve of 0.929, 95% Confidence Interval of 0.875‒0.983, and an optimal cut-off value of 1.397. The expression levels of CRP, IL-6, and NGAL in patients with ACI were higher than those in healthy control groups, p < 0.05; miRNA-122 was positively correlated with CPR, IL-6, NIHSS score, and mRS score. At 48h and 72h, the proliferation rate of HUVECs cells in the miRNA-122 mimics group decreased and the apoptosis rate increased. Cell proliferation rate increased, and apoptosis rate decreased significantly in the groups transfected with miRNA-122 inhibitors. The mRNA and protein levels of pro-apoptotic factors Bax and caspase-3 were significantly increased in the miRNA-122 mimics transfection group, while those of anti-apoptotic factor Bcl-2 were significantly decreased compared to those of the control group. The expression of Bax and Caspase-3 decreased, and the expression of anti-apoptotic factor Bcl-2 increased in the transfected miRNA-122 inhibitors group. mRNA expression levels of Hes1, Notch1, VEGF, and CCNG1 in the miRNA-122 mimic transfected group were significantly decreased, while mRNA expression levels in the miRNA-122 inhibitors transfected group were significantly increased. Bioinformatics showed that there was a miRNA-122 binding site in the 3′UTR region of CCNG1, and dual luciferase assay confirmed that CCNG1 was the target of miRNA-122.

A Chinese Herb Prescription "Fang-gan Decoction" Protects Against Damage to Lung and Colon Epithelial Cells Caused by the SARS-CoV-2 Spike Protein by Regulating the TGF-β/Smad2/3 and NF-κB Pathways / 中国医学科学杂志(英文版)

Objective To explore the effects and mechanisms of a traditional Chinese medicine (TCM) prescription, "Fang-gan Decoction" (FGD), in protecting against SARS-CoV-2 spike protein-induced lung and intestinal injuries in vitro and in vivo.Methods Female BALB/c mice and three cell lines pretreated with FGD were stimulated with recombinant SARS-CoV-2 spike protein (spike protein). Hematoxylin-eosin (HE) staining and pathologic scoring of tissues, cell permeability and viability, and angiotensin-converting enzyme 2 (ACE2) expression in the lung and colon were detected. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of inflammatory factors in serum and cell supernatant. The expression of NF-κB p65, p-NF-κB p65, p-IκBα, p-Smad2/3, TGF-β1, Caspase3, and Bcl-2 was evaluated by Western blotting.Results FGD protected against the damage to the lung and colon caused by the spike protein in vivo and in vitro according to the pathologic score and cell permeability and viability (P<0.05). FGD up-regulated ACE2 expression, which was reduced by the spike protein in the lung and colon, significantly improved the deregulation of inflammatory markers caused by the spike protein, and regulated the activity of TGF-β/Smads and NF-κB signaling.Conclusion Traditional Chinese medicine has a protective effect on lung and intestinal tissue injury stimulated by the spike protein through possible regulatory functions of the NF-κB and TGF-β1/Smad pathways with tissue type specificity.

Identification of SARS-CoV-2 through combined 2nd and 3rd generation sequencing technology / 中国人兽共患病学报

To rapidly and accurately identify novel SARS-CoV-2 variants,we used combined 2nd and 3rd generation sequen-cing technology to sequence and analyze the viral genomes of two specimens from SARS-CoV-2 infection cases imported into Fujian Province.Nanopore and Illumina techniques were used to perform whole genome sequencing of SARS-CoV-2.A pangolin system was used to determine the virus type.Evolutionary analysis software was used to construct the phylogenetic tree.Next-clade was used to analyze the whole genome variation,and estimate ACE2 receptor affinity and immune escape ability.Two complete genome sequences of SARS-CoV-2 were obtained from respiratory specimens from the two cases,with lengths of 29 665 bp and 29 682 bp.The average genome coverage were＞99.0％,and the virus typing results all indicated Omicron BQ.1 lineage.Phylogenetic analysis demonstrated that the two viruses were located in the same cluster of the Omicron BQ.1 line-age.On the basis of these findings and epidemiological data,we speculated that the two cases might have originated from the same infection.Variation analysis indicated that the two viruses shared all 77 mutation sites;except for S:A27S and S:24-26del,all were characteristic mutation sites of the BQ.1 lineage.The predicted ACE2 receptor affinity and immune escape abili-ty scores of the two viruses were both＞0.6,thus suggesting significant changes in their biological characteristics and requiring continuous monitoring and warning.The combined 2nd and 3rd generation sequencing technology was successfully applied to i-dentify the first BQ.1 lineage of the SARS-CoV-2 imported into Fujian Province,considering the timeliness and accuracy of whole genome sequencing,thus providing a technical reference for SARS-CoV-2 variant monitoring.

Geniposide promotes skin ulcer wound healing in diabetic rats through the PI3K/Akt pathway / 中国比较医学杂志

Objective To investigate the protective effect of geniposide against diabetic rats with skin ulcer and the mechanism.Methods Rats were divided into a normal group,model group,and geniposide subgroups(Gen(L):200 mg/kg;Gen(H):500 mg/kg).Diabetic rats were treated with normal saline or geniposide by intragastric administration(n=6).Treatments were administered once a day,and the wound healing and inflammation of each group were recorded every day.After 7 days of treatment for diabetic skin ulcers,the wound area,tissue sections,TUNEL staining and Western blot were used to quantitatively analyze changes in wound healing,apoptosis,and related regulatory protein expression.Results Compared with the model group,the group receiving orally administered geniposide(200 and 500 mg/kg)showed significantly improved wound healing and increased contraction of the injured area.In terms of skin wound apoptosis in diabetic rats,TUNEL-positive cells were significantly reduced in geniposide subgroups(P<0.05).Geniposide significantly inhibited skin inflammation and promoted wound repair,which may be related to promotion of PI3K and Akt phosphorylation.Conclusions Geniposide promoted skin wound repair in diabetic rats by inhibiting inflammatory responses and apoptosis.

Feasibility assessment of Halcyon 3.0 dual-isocenter IMRT plan in postoperative radiotherapy of radical mastectomy for left side of breast cancer / 中国医学装备

Objective:To assess the feasibility of the designed dual-isocenter IMRT plans based on Halcyon 3.0 linear accelerator in postoperative radiotherapy of radical mastectomy for left side of breast cancer.Methods:A total of sixteen patients received the postoperative radiotherapy of radical mastectomy for left side of breast cancer at Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from December 2022 to June 2023 were retrospectively selected.The dual-isocenter plans based respectively on Halcyon 3.0 linear accelerator and Truebeam linear accelerator were designed,and the dosimetric parameters included conformity index(CI)values of target region,homogeneity index(HI)values and doses to organs at risk(OAR)of the two plans were calculated as statistic method.And then,the dosimetric performance of Halcyon 3.0 dual-isocenter plan was compared and analyzed.Utilizing two dose verification tools,ArcCHECK and Portal Dosimetry,to assess the precision of beam delivery of Halcyon 3.0 dual-isocenter plan.Results:The Halcyon dual-isocenter plan and the Truebeam single-isocenter plan had similar plan quality.There were not statistically significant differences(P>0.05)in dosimetric parameters such as CI,HI,exposure dose to 2%of the target volume(D2%)and exposure dose to 98%of the target volume(D98%).Compared to the average monitor unit(MU)of Truebeam single-isocenter plan,the MU values of Halcyon 3.0 dual-isocenter plan increased by 366 MU,while the difference was not statistically significant(P>0.05).The Halcyon 3.0 dual-isocenter plan provided comprehensive protection for OAR,which was better than that of the Truebeam single-isocenter plan.The values of the left side of lung volume(V20)that were covered by 20 Gy dose of the Halcyon 3.0 dual-isocenter plan and the Truebeam single-isocenter plan were respectively 20.41%±1.56%and 24.88%±2.95%,and the difference was statistically significant(t=6.413,P<0.05).There were not significant differences in other OAR dosimetric parameters between the two kinds of plans(P>0.05).The verification pass rates of the Halcyon 3.0 dual-isocenter plans on the ArcCHECK and Portal Dosimetry platforms were respectively 97.6%-98.9%and 98.1%-100%when the ratio of dose tolerance(DT)to distance to agreement(DTA)was set at 2%/2 mm.The verification pass rates of the Halcyon 3.0 dual-isocenter plans on the ArcCHECK and Portal Dosimetry platforms were respectively 99.1%-100%and 99.7%-100%when DT/DTA was set at 3%/3 mm.The beam delivery precision of the Halcyon 3.0 dual-isocenter plan could meet verification standards of clinical treatments.Conclusion:The Halcyon 3.0 dual-isocenter IMRT plan demonstrates a higher feasibility in the postoperative radiotherapy of radical mastectomy for left side of breast cancer.The precision of dose delivery of plan is high,and the dose of target area is sufficient,uniform and favorable conformability.It can effectively limit the OAR exposure dose at the same time.

Construction of a dual fluorescent reporter system for tracing horizontal transfer of mcr-1-carrying plasmid / 中华预防医学杂志

The green fluorescent reporter gene was inserted into the gene interval of polymyxin resistant mcr-1-carrying plasmid (pSH13G841) by homologous recombination of suicide plasmid. At the same time, E. coli J53 with red fluorescent reporter gene was constructed. Using the ability of spontaneous conjugation of drug resistant plasmid (pSH13G841), pSH13G841-GFP plasmid was transferred into J53 RFP bacteria to construct a double fluorescent labeled donor bacterium. The two light-emitting systems could stably and spontaneously express fluorescence without mutual interference. The dual fluorescence report system constructed can be used for visual tracing horizontal transfer of mcr-1-carrying plasmid, the subsequent model can study the colonization, transfer and prognosis of drug-resistant bacteria/drug-resistant genes mcr-1 by using mouse in vivo imaging technology.

Design for online monitoring of occupational hazard factors based on internet of things / 中华劳动卫生职业病杂志

At present, there are disadvantages with the detection for occupational hazard factors, such as insufficient monitoring data, poor timeliness, weak representativeness, long detection cycles, and inability to continuously monitor. Taking advantages of internet of things technology, an online monitoring platform for occupational hazard factors has been designed. The platform collects the concentration (intensity) of hazard factors through sensors, transmits the occupational hazards data collected online in realtime. The online monitoring cloud center for occupational hazard factors processes and analyzes online monitoring data in realtime, stores the hazard factors data to form database management, and provides user application services to form an intelligent online monitoring service model for occupational hazard factors. Based on the online monitoring platform of occupational hazard factors, multi-level government health supervision departments and employers can grasp the status of hazard factors in real time, which is conducive to improving the level of occupational hazard supervision.

Metal artifact reduction and clinical verification in oral and maxillofacial region based on deep learning / 中华口腔医学杂志

Objective: To construct a kind of neural network for eliminating the metal artifacts in CT images by training the generative adversarial networks (GAN) model, so as to provide reference for clinical practice. Methods: The CT data of patients treated in the Department of Radiology, West China Hospital of Stomatology, Sichuan University from January 2017 to June 2022 were collected. A total of 1 000 cases of artifact-free CT data and 620 cases of metal artifact CT data were obtained, including 5 types of metal restorative materials, namely, fillings, crowns, titanium plates and screws, orthodontic brackets and metal foreign bodies. Four hundred metal artifact CT data and 1 000 artifact-free CT data were utilized for simulation synthesis, and 1 000 pairs of simulated artifacts and metal images and simulated metal images (200 pairs of each type) were constructed. Under the condition that the data of the five metal artifacts were equal, the entire data set was randomly (computer random) divided into a training set (800 pairs) and a test set (200 pairs). The former was used to train the GAN model, and the latter was used to evaluate the performance of the GAN model. The test set was evaluated quantitatively and the quantitative indexes were root-mean-square error (RMSE) and structural similarity index measure (SSIM). The trained GAN model was employed to eliminate the metal artifacts from the CT data of the remaining 220 clinical cases of metal artifact CT data, and the elimination results were evaluated by two senior attending doctors using the modified LiKert scale. Results: The RMSE values for artifact elimination of fillings, crowns, titanium plates and screws, orthodontic brackets and metal foreign bodies in test set were 0.018±0.004, 0.023±0.007, 0.015±0.003, 0.019±0.004, 0.024±0.008, respectively (F=1.29, P=0.274). The SSIM values were 0.963±0.023, 0.961±0.023, 0.965±0.013, 0.958±0.022, 0.957±0.026, respectively (F=2.22, P=0.069). The intra-group correlation coefficient of 2 evaluators was 0.972. For 220 clinical cases, the overall score of the modified LiKert scale was (3.73±1.13), indicating a satisfactory performance. The scores of modified LiKert scale for fillings, crowns, titanium plates and screws, orthodontic brackets and metal foreign bodies were (3.68±1.13), (3.67±1.16), (3.97±1.03), (3.83±1.14), (3.33±1.12), respectively (F=1.44, P=0.145). Conclusions: The metal artifact reduction GAN model constructed in this study can effectively remove the interference of metal artifacts and improve the image quality.

Efficacy Evaluation of Apparent Diffusion Coefficient in the Treatment of Uterine Fibroid by Magnetic Resonance Guided Focused Ultrasound Surgery / 中山大学学报(医学科学版)

ObjectiveTo assess the value of apparent diffusion coefficient （ADC） in the treatment of uterine fibroid using magnetic resonance guided focused ultrasound surgery （MRgFUS）. MethodsThe MRI and clinical data of 56 patients with uterine fibroid before， at 3 and 6 months after MRgFUS treatment， at Foshan Hospital of Traditional Chinese Medicine from December 2018 to October 2022， were retrospectively analyzed. The correlation between the ADC value and lesion volume， symptoms severity score （SSS） and uterine fibroid symptoms quality of life questionnaire （UFS-QOL） were analyzed. ANOVA was used to compare the differences in related parameters before and after treatment， and Pearson’s method was performed to analyze data correlation. ResultsThere were significant differences in ADC value ［（1.11±0.13）， （1.84±0.09）， （2.12±0.24），×10-3/（mm2/s）］， lesion volume （102±35.30， 56.70±18.88， 46.93±18.99，cm3）， SSS （36.73±11.74， 21.77±10.21， 17.66±9.30） and UFS-QOL score （59.05±17.48， 76.54±16.50， 82.46±12.37） between before treatment and each time point after treatment （F value was 557.837， 73.589， 53.976 and 37.606， respectively， all P<0.05）. The ADC values were negatively correlated with lesion volume and SSS， and positively correlated with UFS-QOL score， with correlation coefficients of -0.586， -0.630 and 0.592， respectively （all P<0.05）. ConclusionThe ADC value has clinical significance for the treatment of uterine fibroid using MRgFUS.

Bisphenol A induces testicular oxidative stress in mice leading to ferroptosis / 亚洲男科学杂志(英文版)

Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.

The Failure Patterns of Nasopharygeal Carcinoma After Intensity-Modulated Radiotherapy and Implications for Surveillance.

Objective: To investigate the treatment outcomes, failure patterns and surveillance strategy in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). Methods: A cohort of patients with NPC who had received the full course of IMRT between 2008 and 2012 were retrospectively analyzed. The failure patterns, time to recurrence, and detection methods were recorded. The survival was calculated using the Kaplan-Meier method. Multivariate proportional hazard regression models were used to test the prognostic factors. Results: In total, 2607 patients with NPC treated with IMRT were recruited. After the median follow-up of 112 months, 402 (15.4%) patients experienced distant metastasis, 225 (8.6%) patients had local recurrence, and 77 (3.0%) patients had regional recurrences. The 10-year overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 74.5%, 90.1%, and 79.3%, respectively. The factors of male sex, age >50 years, lactate dehydrogenase >245 IU/L, advanced T classification, and advanced N classification were associated with poor OS. The N disease classification was the most important factor in predicting distant metastasis, and advanced T disease classification for high risk of local recurrence. For patients with T1 disease, the incidence of local recurrence was less than 2%, and the incidence of distant metastasis was less than 5% for patients with N0 disease. About 83% of the recurrence occurred in the first 5 years, and 20% of the recurrences showed no symptoms. Conclusion: High rate of local-regional control can be achieved for patients with NPC after IMRT, while distant metastasis remains as the major cause of failures. Patients with advanced N classification has high risk to develop distant metastasis, and most occurred within 5 years. Developing rational and individualized surveillance strategies based on the high risk factors of recurrence is helpful to balance the survival benefit and medical cost.