Mediating effect of cognitive emotion regulation strategy on stress overload and stress response of palliative care nurses / 中国实用护理杂志

Objective:To explore the current status and correlation between stress overload, different cognitive emotion regulation strategies and stress response in palliative care nurses, and to provide reference for reducing stress reaction of hospice nurses.Methods:A total of 448 palliative care nurses from Beijing City, Jiangsu Province, Hunan Province and Anhui Province were selected as subjects by convenience sampling method in February 2022. The general information questionnaire, Stress Overload Scale, Cognitive Emotion Regulation Questionnaire and Stress Response Questionnaire were used to conduct a cross-sectional survey. After analyzing their scores, correlation analysis and mediating effect analysis were conducted.Results:The stress overload score of palliative care nurses was 66.00 (55.00, 67.00), and the stress response score was 80.00 (63.00, 84.00). The stress overload was positively correlated with the stress response ( r=0.735, P<0.05), and the positive emotion regulation strategy was negatively correlated with the stress response ( r=-0.440, P<0.05), negative emotion regulation strategy was positively correlated with stress response ( r=0.747, P<0.05). The cognitive emotion regulation strategy had a partial mediating effect between the stress overload and the stress response, accounting for 29.6% of the total effect. Conclusions:Cognitive emotion regulation is the mediating variable between stress overload and stress response of palliative care nurses. Managers should pay more attention to the stress level and mental health status of palliative care nurses, and guide them to choose appropriate emotional regulation strategies, so as to reduce stress response and maintain physical and mental health.

Expression of RPL32 gene in breast cancer tissues and its effect on proliferation of breast cancer cells / 中华内分泌外科杂志

Objective:To investigate the differences between the expression levels of ribosomal protein L32 (RPL32) in human breast cancer tissue and normal breast tissue and the effects on the proliferation of breast cancer cells.Methods:Paraffin samples of breast cancer tissues and adjacent tissues (more than 3 cm from the tumor margin) were collected from 56 breast cancer patients in the Department of Thyroid and Breast Surgery of the First People's Hospital of Shangqiu City from July 2020 to May 2022. The expression of RPL32 in 56 breast cancer patients and their corresponding paracancer tissues was detected by immunohistochemistry. MCF7 cells were divided into experimental group (ribosomal protein L32, RPL32) and control group (negative control, NC). MCF7 cells in experimental group were transfected with RPL32-siRNA vector, while MCF7 cells in control group were transfected with scramble siRNA vector. RPL32 mRNA content in each group was detected by RT-PCR. The expressions of RPL32 and P53 in the experimental group and control group were detected by western blot. The proliferative ability of cells in each group was detected by CCK8 assay. The clonogenesis ability of each group of cells was detected by clone formation experiment.Results:The positive rate of RPL32 in breast cancer patients was 8.93% (5/56), and the expression rate of RPL32 in paracancer tissues was 78.57% (44/56). The expression rate of RPL32 in breast cancer patients was significantly higher than that in paracancer tissues, with statistical significance ( P=0.007). After transfection with siRNA vector, the mRNA content of RPL32 in MCF7 cells of experimental group and control group decreased, and the protein expression level of RPL32 was 1.09±0.21 and 0.40±0.11, respectively. The expression levels of P53 protein were 1.24±0.32 and 0.37±0.09, respectively. The absorbance of CCK8 at 120 h was 1.11±0.24 and 2.19±0.28, respectively, and the proliferation ability of MCF7 cells in the experimental group was significantly decreased ( P=0.043). The results of clone formation experiment showed that the cell clone formation rate of the experimental group and the control group was (21.11±3.46) % and (58.75±4.29) %, respectively, and the cell clone formation of the experimental group was decreased ( P=0.026) . Conclusions:The expression of RPL32 is significantly increased in breast cancer, which may be related to the malignant degree of breast cancer. Inhibition of RPL32 expression in breast cancer cells affects its proliferation ability.

Effects of combining inspiratory muscle training with diaphragm resistance training on the motor and balance functioning of stroke survivors / 中华物理医学与康复杂志

Objective:To explore the effect of combining inspiratory muscle training with diaphragm resistance training on the respiratory, motor and balance functioning of stroke survivors.Methods:Eighty-eight stroke survivors were randomly divided into a respiratory muscle training group and a control group, each of 44. Both groups received routine rehabilitation, but the respiratory muscle training group also received daily inspiratory muscle and diaphragm resistance training, five days a week for 4 weeks. The respiratory muscle strength, motor function and balance of the two groups were evaluated using the inspiratory muscle strength index, the Fugl-Meyer assessment scale and the Berg balance scale before and after the treatment.Results:After the treatment, the average inspiratory muscle strength index of the respiratory muscle training group was 61.80%, its average Fugl-Meyer score was 75 and its average Berg balance score was 38. All were significantly better than before the treatment and better than the control group′s averages at the same time point. Spearman correlation analysis found significant correlation among the three measurements.Conclusions:Combining inspiratory muscle training with diaphragm resistance training can significantly improve the inspiratory muscle strength of stroke survivors, and promote the recovery of their motor and balance functions.

Competency oriented construction of "Extreme Environment Medicine" Course / 中华医学教育探索杂志

Objective:To construct the curriculum content system of Extreme Environmental medicine based on the trainees' competency.Methods:After analysis of Chinese doctors' post competency demand, and the characteristics of military students, qualitative and quantitative methods were used to construct the curriculum system. The consistency of expert opinions was represented by Kendall's W coefficient, using chi-square test. The hierarchy and weights of all items were analyzed by the analytic hierarchy process, using consistency ratio ( CR) , which was incorporated into this system after passing the test ( CR<0.1) . Results:The selective experts were all authoritative and positivity, the assessments were consistency. Finally, it formed 5 primary items, 15 secondary items, and 54 third items of educational materials and 13 knowledge modules and 1 comprehensive seminar.Conclusions:Based on the demand of Chinese doctors' post competency, a curriculum system of extreme environment medicine has been constructed, through combined application of qualitative and quantitative research methods.

Combination of Antiviral Drugs to Inhibit SARS-CoV-2 Polymerase and Exonuclease as Potential COVID-19 Therapeutics

SARS-CoV-2 has an exonuclease-based proofreader, which removes nucleotide inhibitors such as Remdesivir that are incorporated into the viral RNA during replication, reducing the efficacy of these drugs for treating COVID-19. Combinations of inhibitors of both the viral RNA-dependent RNA polymerase and the exonuclease could overcome this deficiency. Here we report the identification of hepatitis C virus NS5A inhibitors Pibrentasvir and Ombitasvir as SARS-CoV-2 exonuclease inhibitors. In the presence of Pibrentasvir, RNAs terminated with the active forms of the prodrugs Sofosbuvir, Remdesivir, Favipiravir, Molnupiravir and AT-527 were largely protected from excision by the exonuclease, while in the absence of Pibrentasvir, there was rapid excision. Due to its unique structure, Tenofovir-terminated RNA was highly resistant to exonuclease excision even in the absence of Pibrentasvir. Viral cell culture studies also demonstrate significant synergy using this combination strategy. This study supports the use of combination drugs that inhibit both the SARS-CoV-2 polymerase and exonuclease for effective COVID-19 treatment.

Sofosbuvir Terminated RNA is More Resistant to SARS-CoV-2 Proofreader than RNA Terminated by Remdesivir

SARS-CoV-2 is responsible for COVID-19, resulting in the largest pandemic in over a hundred years. After examining the molecular structures and activities of hepatitis C viral inhibitors and comparing hepatitis C virus and coronavirus replication, we previously postulated that the FDA-approved hepatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) might inhibit SARS-CoV-2.1 We subsequently demonstrated that Sofosbuvir triphosphate is incorporated by the relatively low fidelity SARS-CoV and SARS-CoV-2 RNA-dependent RNA polymerases (RdRps), serving as an immediate polymerase reaction terminator, but not by a host-like high fidelity DNA polymerase.2,3 Other investigators have since demonstrated the ability of Sofosbuvir to inhibit SARS-CoV-2 replication in lung and brain cells;4,5 additionally, COVID-19 clinical trials with EPCLUSA6 and with Sofosbuvir plus Daclatasvir7 have been initiated in several countries. SARS-CoV-2 has an exonuclease-based proofreader to maintain the viral genome integrity.8 Any effective antiviral targeting the SARS-CoV-2 RdRp must display a certain level of resistance to this proofreading activity. We report here that Sofosbuvir terminated RNA resists removal by the exonuclease to a substantially higher extent than RNA terminated by Remdesivir, another drug being used as a COVID-19 therapeutic. These results offer a molecular basis supporting the current use of Sofosbuvir in combination with other drugs in COVID-19 clinical trials.

A Library of Nucleotide Analogues Terminate RNA Synthesis Catalyzed by Polymerases of Coronaviruses Causing SARS and COVID-19

SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 worldwide pandemic. We previously demonstrated that five nucleotide analogues inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), including the active triphosphate forms of Sofosbuvir, Alovudine, Zidovudine, Tenofovir alafenamide and Emtricitabine. We report here the evaluation of a library of additional nucleoside triphosphate analogues with a variety of structural and chemical features as inhibitors of the RdRps of SARS-CoV and SARS-CoV-2. These features include modifications on the sugar (2 or 3 modifications, carbocyclic, acyclic, or dideoxynucleotides) or on the base. The goal is to identify nucleotide analogues that not only terminate RNA synthesis catalyzed by these coronavirus RdRps, but also have the potential to resist the viruses exonuclease activity. We examined these nucleotide analogues with regard to their ability to be incorporated by the RdRps in the polymerase reaction and then prevent further incorporation. While all 11 molecules tested displayed incorporation, 6 exhibited immediate termination of the polymerase reaction (Carbovir triphosphate, Ganciclovir triphosphate, Stavudine triphosphate, Entecavir triphosphate, 3-O-methyl UTP and Biotin-16-dUTP), 2 showed delayed termination (Cidofovir diphosphate and 2-O-methyl UTP), and 3 did not terminate the polymerase reaction (2-fluoro-dUTP, 2-amino-dUTP and Desthiobiotin-16-UTP). The coronavirus genomes encode an exonuclease that apparently requires a 2 -OH group to excise mismatched bases at the 3-terminus. In this study, all of the nucleoside triphosphate analogues we evaluated form Watson-Cricklike base pairs. All the nucleotide analogues which demonstrated termination either lack a 2-OH, have a blocked 2-OH, or show delayed termination. These nucleotides may thus have the potential to resist exonuclease activity, a property that we will investigate in the future. Furthermore, prodrugs of five of these nucleotide analogues (Brincidofovir/Cidofovir, Abacavir, Valganciclovir/Ganciclovir, Stavudine and Entecavir) are FDA approved for other viral infections, and their safety profile is well known. Thus, they can be evaluated rapidly as potential therapies for COVID-19.

Triphosphates of the Two Components in DESCOVY and TRUVADA are Inhibitors of the SARS-CoV-2 Polymerase

SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. We previously demonstrated that four nucleotide analogues (specifically, the active triphosphate forms of Sofosbuvir, Alovudine, AZT and Tenofovir alafenamide) inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Tenofovir and emtricitabine are the two components in DESCOVY and TRUVADA, the two FDA-approved medications for use as pre-exposure prophylaxis (PrEP) to prevent HIV infection. This is a preventative method in which individuals who are HIV negative (but at high-risk of contracting the virus) take the combination drug daily to reduce the chance of becoming infected with HIV. PrEP can stop HIV from replicating and spreading throughout the body. We report here that the triphosphates of tenofovir and emtricitabine, the two components in DESCOVY and TRUVADA, act as terminators for the SARS-CoV-2 RdRp catalyzed reaction. These results provide a molecular basis to evaluate the potential of DESCOVY and TRUVADA as PrEP for COVID-19.

Nucleotide Analogues as Inhibitors of SARS-CoV-2 Polymerase

SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously demonstrated that three nucleotide analogues inhibit the SARS-CoV RNA-dependent RNA polymerase (RdRp). Here, using polymerase extension experiments, we have demonstrated that the active triphosphate form of Sofosbuvir (a key component of the FDA approved hepatitis C drug EPCLUSA), is incorporated by SARS-CoV-2 RdRp, and blocks further incorporation. Using the same molecular insight, we selected the active triphosphate forms of three other anti-viral agents, Alovudine, AZT (an FDA approved HIV/AIDS drug) and Tenofovir alafenamide (TAF, an FDA approved drug for HIV and hepatitis B) for evaluation as inhibitors of SARS-CoV-2 RdRp. We demonstrated the ability of these three viral polymerase inhibitors, 3-fluoro-3-deoxythymidine triphosphate, 3-azido-3-deoxythymidine triphosphate and Tenofovir diphosphate (the active triphosphate forms of Alovudine, AZT and TAF, respectively) to be incorporated by SARS-CoV-2 RdRp, where they also terminate further polymerase extension. These results offer a strong molecular basis for these nucleotide analogues to be evaluated as potential therapeutics for COVID-19.

Nucleotide Analogues as Inhibitors of SARS-CoV Polymerase

SARS-CoV-2, a member of the coronavirus family, has caused a global public health emergency.1 Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously reasoned that the FDA-approved heptatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) should inhibit coronaviruses, including SARS-CoV-2.2 Here, using model polymerase extension experiments, we demonstrate that the activated triphosphate form of Sofosbuvir is incorporated by low-fidelity polymerases and SARS-CoV RNA-dependent RNA polymerase (RdRp), and blocks further incorporation by these polymerases; the activated triphosphate form of Sofosbuvir is not incorporated by a host-like high-fidelity DNA polymerase. Using the same molecular insight, we selected two other anti-viral agents, Alovudine and AZT (an FDA approved HIV/AIDS drug) for evaluation as inhibitors of SARS-CoV RdRp. We demonstrate the ability of two HIV reverse transcriptase inhibitors, 3-fluoro-3-deoxythymidine triphosphate and 3-azido-3-deoxythymidine triphosphate (the active triphosphate forms of Alovudine and AZT), to be incorporated by SARS-CoV RdRp where they also terminate further polymerase extension. Given the 98% amino acid similarity of the SARS-CoV and SARS-CoV-2 RdRps, we expect these nucleotide analogues would also inhibit the SARS-CoV-2 polymerase. These results offer guidance to further modify these nucleotide analogues to generate more potent broad-spectrum anti-coronavirus agents.

Nucleotide Analogues as Inhibitors of Viral Polymerases

Coronaviruses such as the newly discovered virus from Wuhan, China, 2019-nCoV, and the viruses that cause SARS and MERS, have resulted in regional and global public health emergencies. Based on our molecular insight that the hepatitis C virus and the coronavirus use a similar viral genome replication mechanism, we reasoned that the FDA-approved drug EPCLUSA (Sofosbuvir/Velpatasvir) for the treatment of hepatitis C will also inhibit the above coronaviruses, including 2019-nCoV. To develop broad spectrum anti-viral agents, we further describe a novel strategy to design and synthesize viral polymerase inhibitors, by combining the ProTide Prodrug approach used in the development of Sofosbuvir with the use of 3-blocking groups that we have previously built into nucleotide analogues that function as polymerase terminators.

Repair of infective foot ulcer of small area with free peroneal artery perforator flap / 中华显微外科杂志

Objective To investigate the clinical effect of infective foot ulcer and soft tissue defects of small area with free peroneal artery perforator flap.Methods From February,2016 to Apirl,2017,9 cases of infective foot ulcer and soft tissue defect of small area were repaired with peroneal artery perforator flap.Cause of infection:injury in 6 cases,diabetes in 2 cases,spinal cord injury subsequent pressure sore in 1 case.Infective ulcer part:4 cases on plantar metatarsophalangeal joint,2 cases on dorsal metatarsophalangeal joint,2 cases on interior of the first metatarsophalangeal joint and 1 case on the heel.Defect area:3.0 cm×2.0 cm-5.0 cm×3.0 cm;flap area:4.0 cm×3.5 cm-7.0 cm×4.5 cm.The donor sites were sutured directly.All the flaps contained lateral sural cutaneous nerve.In order to rebuild the sensation of flaps,nerves between surgical area and receiving area were received end-to-side anastomosis.Outpatient follow-up was used in all patients.Results All the flaps survived,and all the wounds were primary healed,without recurrence of infection.All patients were followed-up from 6 to 24 months with an average of 16 months.The appearance of flaps was good with slight bloated.The texture and color of the flaps were close to the recipient site.Flap feel was good except the cases of diabetes and spinal cord injury pressure sore.The AOFAS score at last follow-up time was 80.05±7.80,which was excellent in 5 cases,good in 2 cases,and fair in 2 cases.Conclusion The free peronerl artery perforator flap has many advantages,such as vascular anatomy constant,blood supply is reliable,thickness moderate,easy to get,strong resistance to infection,small district damage,etc.It is a useful clinical method to repair foot infection ulcer and soft issue defects of small area.

Precision repairing of compound tissue defect at limbs by 3-Dimentional contrast printing and fibular head compound tissue flap transplantation / 中华显微外科杂志

Objective To explore the clinical application and effect of fibular head compound soft tissue flap transplantation on precision repairing of compound tissue defect at limb joints assisted by 3-Dimensional contrast printing technology.Methods From March,2014 to September,2017,9 patients with bone and soft tissue defect at limb joints were selected.In which,2 were distal radius bone defect with joint capsule and ligament defect,2 were lower segment tibia bone and soft tissue defect,2 were femur under section of the bone and soft tissue defect,2 were medial malleolus bone and ligament defect,and 1 was external ankle ligament and bone defect.Using 3-Dimensional printing to conduct bilateral mirror-image contrast prior to the operation,morphology of bone defect at limb joints was acquired.Based on the texture printed out,corresponding fibular head compound blocks with blood vessels were removed from the donor site and transplanted to the recipient site before anastomosing the blood vessels and restoring the blood flow.The regular post-operative followed-up was performed.Results The 9 transplanted tissue blocks survived.The donor sites and the recipient sites were healed.The followed-up for restoration of limb function was from 9 to 35 (average,17.5) months.The ankle function was assessed according Kofoed scale,resulted in 2 excellent and 1 good;The wrist function was assessed according Mayo scale,resulted in 1 excellent and 1 good.The medial malleolus bone defect and criteria bone defect were healed at 6 months.The patients were satisfied with the efficacy.Conclusion The application of 3-Dimensional contrast printing of fibular head compound tissue flap transplantation in repairing compound tissue defects at limb joints can reduce damage to the donor site,realizing precise repairing on limb tissue defect,and make good function restoration.

Research of Unidirectional Ion Ejection in Printed-Circuit-Board Ion Trap / 分析化学

Printed-circuit-board ion trap (PCBIT) is a novel ion trap mass analyzer,which is capable of optimizing its internal electric field distributions by adjusting the radio frequency (RF) voltage-divided ratio to improve its analytical performance.This work introduced odd electric field components into the trapping volume to achieve unidirectional ion ejection by applying asymmetric RF voltages to x electrode pairs of PCBIT.In this case,the center of ion vibration was displaced away from the geometrical center of PCBIT and ions were ejected predominantly through one of x electrode pairs.The relationship between asymmetric voltage-divided ratio (AV) and internal electric field distributions was investigated by simulation software SIMION and AXSIM.At the same time,the ion trajectories and simulated mass spectrum peaks were calculated.The results showed that,for ions with m/z 609 Th,a mass resolution over 2500 and an ion unidirectional ejection efficiency of over 90％ were achieved in PCBIT with AV=20％ at an appropriate frequency of AC.Using this method,ion unidirectional ejection efficiency of PCBIT can be significantly improved while maintaining a high mass resolution,which makes the PCBIT more suitable for developing miniaturized mass spectrometer.

Co-word clustering analysis for hot research areas of human caring based on PubMed / 中华护理杂志

Objective To identify hot research areas of nursing human caring in PubMed from 2012 to 2016, and to explore the present research status and development directions. Methods PubMed was searched using key words human caring. BICOMB 2.0 and SPSS 11.5 software were used to analyze high-frequency keywords and conduct co-word clustering analysis. Results We searched for 3088 related articles and extracted 42 high-frequency keywords (30.97%). Seven hot research areas were identified,including:human caring in nursing practice;nursing models,nursing theories;nursing education of human caring;hospice care;relationship between human caring and nurse-patient relation;human caring of cancer patients;family system,social support and human caring. Conclusion Analysis of research areas of nursing human caring in past 5 years is beneficial to understanding the present research status and development directions,and providing references for practice,research and education of human caring.

The effect of triamcinolone acetonide dental paste in the treatment of erosive oral lichen planus / 实用口腔医学杂志

60 patients with pathologically diagnosed erosive lichen planus of bilateral buccal mucosa were included.The lesion on one side was treated by local application of triamcinolone acetonide dental paste(test group),the lesion on the other side without treatment was used in the control group.7,1 4,21 and 28 d after treatment the pain level and the lesion situation scores in the test group decreased significantly (P <0.001 ),and lower than those in the control group at the same time point(P <0.05).No adverse reaction was found in the 2 groups. Triamcinolone Acetonide Dental Paste is effective in the treatment of erosive oral lichen planus.

Design and application research of PE right ventricular catheter for mice / 重庆医学

Objective To establish a simple ,low cost and stable method to detect right ventricular pressure in mice .Methods A PE-50 duct length 15 cm(outside diameter :0 .9 mm ,inner diameter :0 .5 mm) was bent on one terminal and the other terminal was inserted into a 7# syringe needle to connect to a pressure transducer .This duct was intubated into right ventricle via right external jugular vein to detect right ventricular pressure in 80 SPF grade male C57BL/6 mice .Successful cases and operation time were re-corded .Besides ,40 SPF grade male C57BL/6 mice were randomized into the control group (n=20) and chronic hyperbaric hypoxia group(n= 20) .Mice in chronic hyperbaric group were raised in a hyperbaric chamber of simulated 5 000 m high altitude for 4 weeks .The control group was raised outside the chamber simultaneously .Right ventricular systolic pressure was detected with the PE duct .Left and right ventricles were detached and weighed ,and Hermann-Willson index was calculated .Results With this PE duct ,right ventricular intubation success rate was 90% (72/80) ,the operation cost approximately 3 to 5 min each mouse from the separation of blood vessels to detect the time needed for the right ventricle waveform .right ventricular systolic pressure[(39 .52 ± 4 .34 )mm Hg] and Hermann-Willson index(0 .356 ± 0 .039)of chronic hyperbaric hypoxia group were significantly higher than that of control group [(21 .24 ± 2 .7)mm Hg and (0 .256 ± 0 .020)] ,which has significant positive correlation (P<0 .01) .Conclusion It is simple ,fast ,stable ,costing low and of high success ratio to detect right ventricular pressure with this method .

On the segmentation of malignant halo in ultrasound images of breast tumor / 生物医学工程学杂志

The method for segmenting malignant halo of malignant breast tumor in ultrasound image is useful in providing evidence for the differential diagnosis of breast tumor. In this respect, we adopt an improved anisotropic diffusion filtering method to preprocess the breast tumor ultrasound image, and then apply an improved LBF model with combination of Otsu and morphology methods to extract internal and external contours for obtaining malignant halo based on LBF model proposed by Li. We compare our data of malignant halo with doctor's manual-sketched malignant halo, and make quantitative analysis. The result shows that the malignant halo segmented by the proposed methods in this paper is in accordance with the manual-sketched malignant halo.

A Comparison of some bioactivitiex of A Ⅱ made in China and oversedas / 中国药理学通报

The bioactive identity of A Ⅱ made in China and overseas was demonstrated in different levers including receptor, organ and whole body in this report. Therefore, the A Ⅱ made in China can be used in various pharmacological researches in stead of imports.