Structure-based design of novel heterocycle-substituted ATDP analogs as non-nucleoside reverse transcriptase inhibitors with improved selectivity and solubility

Following on our recently developed biphenyl-ATDP non-nucleoside reverse transcriptase inhibitor ZLM-66 (SI = 2019.80, S = 1.9 μg/mL), a series of novel heterocycle-substituted ATDP derivatives with significantly improved selectivity and solubility were identified by replacement of the biphenyl moiety of ZLM-66 with heterocyclic group with lower lipophilicity. Evidently, the representative analog 7w in this series exhibited dramatically enhanced selectivity and solubility (SI = 12,497.73, S = 4472 μg/mL) in comparison with ZLM-66 (SI = 2019.80, S = 1.9 μg/mL). This new NNRTI conferred low nanomolar inhibition of wild-type HIV-1 strain and tested mutant strains (K103N, L100I, Y181C, E138K, and K103N + Y181C). The analog also demonstrated favorable safety and pharmacokinetic profiles, as evidenced by its insensitivity to CYP and hERG, lack of mortality and pathological damage, and good oral bioavailability in rats (F = 27.1%). Further development of 7w for HIV therapy will be facilitated by this valuable information.

The role of inflammation in heart failure with preserved ejection fraction / 生理学报

Heart failure with preserved ejection fraction (HFpEF) is a type of heart failure characterized by left ventricular diastolic dysfunction with preserved ejection fraction. With the aging of the population and the increasing prevalence of metabolic diseases, such as hypertension, obesity and diabetes, the prevalence of HFpEF is increasing. Compared with heart failure with reduced ejection fraction (HFrEF), conventional anti-heart failure drugs failed to reduce the mortality in HFpEF due to the complex pathophysiological mechanism and multiple comorbidities of HFpEF. It is known that the main changes of cardiac structure of in HFpEF are cardiac hypertrophy, myocardial fibrosis and left ventricular hypertrophy, and HFpEF is commonly associated with obesity, diabetes, hypertension, renal dysfunction and other diseases, but how these comorbidities cause structural and functional damage to the heart is not completely clear. Recent studies have shown that immune inflammatory response plays a vital role in the progression of HFpEF. This review focuses on the latest research progress in the role of inflammation in the process of HFpEF and the potential application of anti-inflammatory therapy in HFpEF, hoping to provide new research ideas and theoretical basis for the clinical prevention and treatment in HFpEF.

Picomolar inhibitor of reverse transcriptase featuring significantly improved metabolic stability

Considering the undesirable metabolic stability of our recently identified NNRTI 5 (t1/2 = 96 min) in human liver microsomes, we directed our efforts to improve its metabolic stability by introducing a new favorable hydroxymethyl side chain to the C-5 position of pyrimidine. This strategy provided a series of novel methylol-biphenyl-diarylpyrimidines with excellent anti-HIV-1 activity. The best compound 9g was endowed with remarkably improved metabolic stability in human liver microsomes (t1/2 = 2754 min), which was about 29-fold longer than that of 5 (t1/2 = 96 min). This compound conferred picomolar inhibition of WT HIV-1 (EC50 = 0.9 nmol/L) and low nanomolar activity against five clinically drug-resistant mutant strains. It maintained particularly low cytotoxicity (CC50 = 264 μmol/L) and good selectivity (SI = 256,438). Molecular docking studies revealed that compound 9g exhibited a more stable conformation than 5 due to the newly constructed hydrogen bond of the hydroxymethyl group with E138. Also, compound 9g was characterized by good safety profiles. It displayed no apparent inhibition of CYP enzymes and hERG. The acute toxicity assay did not cause death and pathological damage in mice at a single dose of 2 g/kg. These findings paved the way for the discovery and development of new-generation anti-HIV-1 drugs.

Recent development on COX-2 inhibitors as promising anti-inflammatory agents: The past 10 years

Cyclooxygenases play a vital role in inflammation and are responsible for the production of prostaglandins. Two cyclooxygenases are described, the constitutive cyclooxygenase-1 and the inducible cyclooxygenase-2, for which the target inhibitors are the non-steroidal anti-inflammatory drugs (NSAIDs). Prostaglandins are a class of lipid compounds that mediate acute and chronic inflammation. NSAIDs are the most frequent choices for treatment of inflammation. Nevertheless, currently used anti-inflammatory drugs have become associated with a variety of adverse effects which lead to diminished output even market withdrawal. Recently, more studies have been carried out on searching novel selective COX-2 inhibitors with safety profiles. In this review, we highlight the various structural classes of organic and natural scaffolds with efficient COX-2 inhibitory activity reported during 2011-2021. It will be valuable for pharmaceutical scientists to read up on the current chemicals to pave the way for subsequent research.

Epidemiological characteristics and influencing factor of non-occupational carbon monoxide poisoning during 2007—2018 in Shanghai / 环境与职业医学

Background Non-occupational carbon monoxide (CO) poisoning is a public health problem that seriously affect people’s health and lives. Objective To describe the prevalence of non-occupational CO poisoning during 2007—2018 in Shanghai, analyze its epidemiological characteristics and potential influencing factors, and explore effective prevention and control measures. Methods Daily reported non-occupational CO poisoning cases and meteorological factors from 2007 to 2018 were collected in Shanghai, epidemiological characteristics were analyzed by descriptive epidemiology methods, and a distributed lag nonlinear model was used to assess the association between temperature and non-occupational CO poisoning. Results A total of 2264 non-occupational CO poisoning events and 3866 cases from 2007 to 2018 were reported in Shanghai, including 59 death cases. More than half of the poisoning cases were female (56.3%), and young adults accounted for more cases than any other age group (54.8%). The poisoning events mainly occurred in winter (from December to next February); however, cases reported in summer increased in recent years. The peak period of the events was from 20:00 to 24:00. Households (85.2%) and restaurants (8.0%) were the common places of non-occupational CO poisoning events, and the main cause was improper use of gas water heater (36.9%). A nonlinear curve was found between daily average temperature of current day and the occurrence of non-occupational CO poisoning. Temperature was negatively associated with the risk of non-occupational CO poisoning when the temperature was lower than 9.6 ℃, while a positive association was found during 9.7-26.0 ℃. Conclusion Winter is a high season for non-occupational CO poisoning in Shanghai, rising cases reported in summer is also worthy of attention. Supervision should be strengthened to ban sales of unqualified gas water heaters, and health education on CO poisoning prevention and control should be conducted through multiple channels, in order to reduce the incidence of CO poisoning.

Characterization and phylogenetic analysis of the complete chloroplast genome of Lycopus europaeus / 药学学报

We intend to study the structural characteristics of Lycopus europaeus Linn. chloroplast genome and compare the evolutionary relationship of species from Lamiaceae with similar medicinal effects. The total DNA of Lycopus europaeus was sequenced using the Illumina Hiseq 4000 Sequencing platform and was assembled using NOVOplasty software. And then we annotated and analyzed the genome using the CPGAVAS2 online tool. We constructed the phylogenetic tree using the Stellera chamaejasme and Potentilla chinensis as the outgroup. The whole length of Lycopus europaeus chloroplast genome was 152 085 bp. A total of 132 genes were annotated including 88 protein-coding genes, 8 rRNA genes and 36 tRNA genes. Among them, 8 protein-coding genes (ndhB, rps7, rps12, rps19, rpl2, rpl23, ycf2, ycf15), 7 tRNA coding genes (trnM-CAU, trnL CAA, trnN-GUU, trnE-UUC, trnV-GAC, trnA-UGC, trnR-ACG) and 4 rRNA coding genes (rrn16s, rrn23s, rrn4.5s, rrn5s) are located in the IR region. There are 13 protein coding genes [rps16, rps19 (×2), atpF, rpoC1, rpl2 (×2), petB, petD, rpl16, ndhB (×2), ndhA] each contains one intron, two protein-coding genes (ycf3, clpP) each contain two introns, and 8 tRNA coding genes each contain one intron. A total of 34 SSRs were detected in the chloroplast genome of Lycopus europaeus. Phylogenetic analysis revealed that two species in the Lycopus genus, four species in the Dracocephalum genus, Glechoma longituba, two species in the Mentha genus and Prunella vulgari, in total 10 species are most related. The complete genome sequence of Lycopus europaeus was obtained and analyzed, which clarified the evolutional relationship between the species of Lycopus europaeus and in the Lamiaceae family.

Cardiac Protection Mechanism and Clinical Application of Dexmedetomidine / 中国医学科学院学报

Dexmedetomidine is an α2 adrenoceptor agonist and has cardioprotective effect,the mechanism of which is being studied.Increasing studies have proved the clinical value of dexmedetomidine in reducing postoperative complications and improving the prognosis of patients.Therefore,this review summarizes the cardiac protection mechanism of dexmedetomidine based on the existing studies and expounds the application of dexmedetomidine in the perioperative period of cardiovascular surgery.

Mediating effect of psychological resilience between perceived organizational support and presenteeism among medical staff in the prevention and control of COVID-19 / 中国职业医学

@#Objective （ ） To explore the influence of perceived organizational support POS and psychological resilience on （ - ）Methods presenteeism behavior in medical staff in the prevention and control of coronavirus disease COVID 19 . Doctors - - and nurses engaged in the front line work of prevention and control in the four designated hospitals for the treatment of COVID ， 19 in Guangdong Province Hunan Province and Jiangsu Province were selected as the research subjects using a random cluster ， - - sampling method. The Survey of Perceived Organizational Support Scale the 10 item Connor Davidson Resilience Scale and - ， Results Standford Presenteeism Scale 6 were used to investigate their POS psychological resilience and presenteeism. The ， （ ），（ ） （ ）， total scores of POS psychological resilience and presenteeism were 44.9±7.6 31.2±5.7 and 18.5±3.7 respectively. （ Both POS and psychological resilience had negative effect on presenteeism standardized regression coefficient were −0.59 ， P ） ［ and −0.38 both <0.01 . Psychological resilience played a partial mediating role between POS and presenteeism 95% （ - ）， ］ Conclusion confidence interval −0.22 −0.09 the mediating effect ratio was 23.4% . Both POS and psychological - ， resilience can directly affect the presenteeism behavior of medical staff in COVID 19 prevention and control and POS can also indirectly affect their presenteeism by affecting psychological resilience.

Mediating effect of psychological resilience between perceived organizational support and presenteeism among medical staff in the prevention and control of COVID-19 / 中国职业医学

@#Objective （ ） To explore the influence of perceived organizational support POS and psychological resilience on （ - ）Methods presenteeism behavior in medical staff in the prevention and control of coronavirus disease COVID 19 . Doctors - - and nurses engaged in the front line work of prevention and control in the four designated hospitals for the treatment of COVID ， 19 in Guangdong Province Hunan Province and Jiangsu Province were selected as the research subjects using a random cluster ， - - sampling method. The Survey of Perceived Organizational Support Scale the 10 item Connor Davidson Resilience Scale and - ， Results Standford Presenteeism Scale 6 were used to investigate their POS psychological resilience and presenteeism. The ， （ ），（ ） （ ）， total scores of POS psychological resilience and presenteeism were 44.9±7.6 31.2±5.7 and 18.5±3.7 respectively. （ Both POS and psychological resilience had negative effect on presenteeism standardized regression coefficient were −0.59 ， P ） ［ and −0.38 both <0.01 . Psychological resilience played a partial mediating role between POS and presenteeism 95% （ - ）， ］ Conclusion confidence interval −0.22 −0.09 the mediating effect ratio was 23.4% . Both POS and psychological - ， resilience can directly affect the presenteeism behavior of medical staff in COVID 19 prevention and control and POS can also indirectly affect their presenteeism by affecting psychological resilience.

Mediating effect of psychological resilience between perceived organizational support and presenteeism among medical staff in the prevention and control of COVID-19 / 中国职业医学

@#Objective （ ） To explore the influence of perceived organizational support POS and psychological resilience on （ - ）Methods presenteeism behavior in medical staff in the prevention and control of coronavirus disease COVID 19 . Doctors - - and nurses engaged in the front line work of prevention and control in the four designated hospitals for the treatment of COVID ， 19 in Guangdong Province Hunan Province and Jiangsu Province were selected as the research subjects using a random cluster ， - - sampling method. The Survey of Perceived Organizational Support Scale the 10 item Connor Davidson Resilience Scale and - ， Results Standford Presenteeism Scale 6 were used to investigate their POS psychological resilience and presenteeism. The ， （ ），（ ） （ ）， total scores of POS psychological resilience and presenteeism were 44.9±7.6 31.2±5.7 and 18.5±3.7 respectively. （ Both POS and psychological resilience had negative effect on presenteeism standardized regression coefficient were −0.59 ， P ） ［ and −0.38 both <0.01 . Psychological resilience played a partial mediating role between POS and presenteeism 95% （ - ）， ］ Conclusion confidence interval −0.22 −0.09 the mediating effect ratio was 23.4% . Both POS and psychological - ， resilience can directly affect the presenteeism behavior of medical staff in COVID 19 prevention and control and POS can also indirectly affect their presenteeism by affecting psychological resilience.

Research progress on functional assessment and rehabilitation treatment of vascular cognitive impairment / 中国基层医药

Vascular cognitive impairment is a common type of cognitive impairment. At present, there is no targeted treatment, especially for moderate to severe dementia. This review focuses on the early functional evaluation and rehabilitation treatment in patients with vascular cognitive impairment, in order to obtain optimal curative effects and improve the quality of daily living. Neuropsychological test is helpful for early screening of vascular cognitive impairment. Neuropsychological test, together with the results of neuroelectrophysiology and imaging examination as objective evidence, can further predict the disease progress and can be used to guide rehabilitation treatment and curative effect evaluation. Cognitive training, exercise training, non-invasive nerve regulation technology, acupuncture and moxibustion are currently effective rehabilitation treatments. Combined application of various methods has a better improvement effect than monotherapy. Among them, non-invasive nerve regulation technology shows a good application prospect. At present, more high-quality clinical research evidence is needed.

Analysis on the factors that influence the treatment outcome of Tibetan nationality new smear-positive pulmonary tuberculosis patients in Qinghai Province / 中华疾病控制杂志

@#Objective To analyze the treatment outcome and related influencing factors of Tibet- an nationality new smear-positive pulmonary tuberculosis patients in Qinghai Province，so as to provide evidence for tuberculosis control and treatment among Tibetan population． Methods Statistical analysis was conducted on 5 564 Tibetan nationality new smear-positive pulmonary tuberculosis cases in Qinghai province who were reported in the China Tuberculosis Information Management System and approved to receive treatment from 2008 to 2017． The main influencing factors were detected by unconditional Logistic regression model analysis，dependent variable was successful treatment or not，independent variables were other factors related to the treatment outcome． Ｒesults The treatment success rate of Tibetan nationality new smear-positive pulmonary tuberculosis cases was 87. 1% ( 4 848 /5 564) ，and the adverse outcome rate was 12. 9% ( 716 /5 564) ． Unconditional Logistic regression model analysis indicated that non-full- course supervision management，living in agricultural and pastoral area，having severe disease，floating population，and age older than 60 years were risk factors of adverse outcome． The odds ratio( OＲ) 95% confidence interval( CI) of the above risk factors were 13. 044( 10. 671-15. 944) ，2. 305( 1. 703-3. 119) ， 2. 090( 1. 346-3. 243) ，1. 967( 1. 443-2. 682) ，and 1. 909( 1. 410-2. 586) ． Clinical consultation，farmers and herdsmen were protective factors． The OＲ( 95% CI) were 0. 451( 0. 375-0. 543) ，and 0. 786( 0. 627- 0. 985) ． Conclusions Treatment success rate of Tibetan nationality new smear positive pulmonary tuberculosis cases was low． Therefore，the directly observed treatment short-course ( DOTS) strategy should be strictly implemented and the full-course supervision management should be strengthened to improve the treatment success rate． More attention should be paid to the elderly，severe，floating，agricultural and pastoral populations among the Tibetan population．

Advance in Sarcopenia-related Dysphagia (review) / 中国康复理论与实践

Sarcopenia is an age-related syndrome of extensive, aggressive muscle mass loss and function reducing, which seriously affects the quality of life and social participation of the elderly. Dysphagia can increase the prevalence of sarcopenia, in another hand, sarcopenia can also implicate swallow related muscles, to increase the risk of malnutrition and aspiration. In recent years, the concept of sarcopenic dysphagia has been widely recognized in many researches. Sarcopenia is mainly screened with CT, MRI, ultrasound, and other auxiliary examination, as well as consensus guidelines. Interventions for it mainly include functional training, nutrition management and drug therapy. Early identification and intervention are important for the outcome and quality of life of patients.

Progress of pathogenesis in Burkitt lymphoma / 白血病·淋巴瘤

Burkitt lymphoma (BL) is a highly aggressive B-cell non-Hodgkin lymphoma (NHL) derived from germinal center B cells, which can be divided into endemic, sporadic and immunodeficiency-associated types. BL is characterized by c-myc deregulation due to translocation of c-myc gene to an immunoglobulin enhancer region, resulting in excessive cell proliferation and rapid tumor progression, however the dysregulation of myc alone can't explain the pathogenesis and progression of BL. With the development of molecular biology technology in recent years, the further research on molecular mechanisms of BL pathogenesis may provide a theoretical basis of for clinical diagnosis and targeted drug therapy. This review discusses the progress of pathogenesis in BL.

Progress of pathogenesis in Burkitt lymphoma / 白血病·淋巴瘤

Burkitt lymphoma (BL) is a highly aggressive B-cell non-Hodgkin lymphoma (NHL) derived from germinal center B cells, which can be divided into endemic, sporadic and immunodeficiency-associated types. BL is characterized by c-myc deregulation due to translocation of c-myc gene to an immunoglobulin enhancer region, resulting in excessive cell proliferation and rapid tumor progression, however the dysregulation of myc alone canˊt explain the pathogenesis and progression of BL. With the development of molecular biology technology in recent years, the further research on molecular mechanisms of BL pathogenesis may provide a theoretical basis of for clinical diagnosis and targeted drug therapy. This review discusses the progress of pathogenesis in BL.

Noise attenuation analysis on auditory evoked potential based on maximum length sequence / 生物医学工程学杂志

The maximum length sequence (m-sequence) has been successfully used to study the linear/nonlinear components of auditory evoked potential (AEP) with rapid stimulation. However, more study is needed to evaluate the effect of the m-sequence order in terms of the noise attenuation performance. This study aimed to address this issue using response-free electroencephalogram (EEG) and EEGs with nonlinear AEPs. We examined the noise attenuation ratios to evaluate the noise variation for the calculations of superimposed averaging and cross-correlation, respectively, which constitutes the main process in the deconvolution method using the dataset of spontaneous EEGs to simulate the cases of different orders (order 5 to 12) of m-sequences. And an experiment using m-sequences of order 7 and 9 was performed in true cases with substantial linear and nonlinear AEPs. The results demonstrate that the noise attenuation ratio is well agreed with the theoretical value derived from the properties of m-sequences on the random noise condition. The comparison of waveforms for AEP components from two m-sequences showed high similarity suggesting the insensitivity of AEP to the m-sequence order. This study provides a more comprehensive solution to the selection of m-sequences which will facilitate the feasible application on the nonlinear AEP with m-sequence method.

Analysis of the results of Treponema Pallidum DNA in serum and vaginal fluid of patients with latent syphilis before and after treatment / 中华传染病杂志

Objective To investigate the infectivity of serum and vaginal fluid in early cases and late latent cases of syphilis .Methods From January 2015 to December 2015 ,sixty-eight female patients with latent syphilis were enrolled in the outpatient clinic of Ningbo Women and Children′s Hospital ,including 38 early cases and 30 late cases .Tolulized red unheated serum test (TRUST ) was detected by using kits and Treponema Pallidum DNA (TP-DNA) was detected by polymerase chain reaction .TP-DNA levels in serum and vaginal fluid were compared before and after benzathine penicillin treatment in patients with early and late latent syphilis .Chi square test was performed for count data analysis .Results TRUST negative conversion cases in early latent syphilis after 3 ,6 and 12 months of treatment were 11 (28 .9％ ) , 16 (42 .1％ ) and 27 (71 .0％ ) ,respectively .TRUST negative conversion cases in late latent syphilis after 3 ,6 and 12 months of treatment were 6 (20 .0％ ) ,12 (40 .0％ ) and 14 (46 .7％ ) ,respectively .There were no statistical differences in TRUST negative conversion rates after 3 months and 6 months after treatment between early cases and late cases (χ2= 0 .716 and 0 .031 ,respectively ,both P> 0 .05) ,while those after 12 months of treatment between early cases and late cases were statistical different (χ2=4 .164 ,P < 0 .05) .The vaginal fluid TP-DNA positive cases in early syphilis before and after 3 ,6 ,and 12 months of treatment were 4 (10 .5％ ) ,0 ,1 (2 .63％ ) and 1 (2 .63％ ) ,respectively ,with no statistical difference (χ= 6 .247 ,P> 0 .05) .The serum TP-DNA positive cases in early syphilis before and after 3 , 6 ,and 12 months of treatment were 18 (47 .3％ ) ,4 (10 .5％ ) ,5 (13 .2％ ) and 5 (13 .2％ ) ,respectively , with statistical difference (χ= 21 .217 , P < 0 .05 ) . The vaginal fluid TP-DNA positive cases in late syphilis before and after 3 ,6 , and 12 months of treatment were 2 (6 .7％ ) ,0 ,0 and 1 (3 .3％ ) , respectively ,with no statistical difference (χ2= 3 .761 , P> 0 .05) .The serum TP-DNA positive cases in late syphilis before and after 3 ,6 ,and 12 months of treatment were 8 (26 .7％ ) ,1 (3 .3％ ) ,1 (3 .3％ ) and 1 (3 .3％ ) ,respectively ,with statistical difference (χ2= 14 .712 , P < 0 .05) .Conclusions Standard treatment can reduce the level of TP in serum and vaginal fluid of latent syphilis women and improve the negative conversion rate of TRUST .Late latent syphilis is easier to create sero-resistance than early cases . The early cases have stronger infectivity than late cases before standard treatment .

Implementation and establishment of rapid response system for non-hospitalized patients / 中华护理杂志

We established the rapid response system for non-hospitalized patients from 2012 in order to improve the effectiveness of emergent critical care for non-hospitalized patients when emergency happened.From January 2013 to December 2016,there were 122 cases with RRS activation for non-hospitalized patients.The time to arrive was 3.16±0.41 min,and 107 cases(86.89％)were sent to the emergency department.Fifteen patients(14.02％)were classified as level 1,26(24.03％)as level Ⅱ,48(16.82％)as level Ⅲ,and 18(16.82％) as level ⅣV,and 83％ were critical patients.Rapid response system is important to cope with emergency in non-hospitalized patients.

Effect and prognosis of treatment of lobar pneumonia with latamoxet / 中国生化药物杂志

Objective To investigate the therapeutic effect of cefradine on lobar pneumonia and its influence on the prognosis of patients with lobar pneumonia. Methods 90 cases of lobar pneumonia patients from December 2015 to May 2017 were randomly divided into the study group and the control group, with 45 cases in each group. The study group was treated with latamoxef on the basis of routine treatment, the control group was treated with cefoperazone on the basis of routine treatment ,recorded in two groups after 2 weeks of treatment. The clinical efficacy,drug related adverse reactions occur of the two groups were recorded after two weeks of treatment. Results The total effective rate in the study group(93.33%) was significantly higher than that of the control group(73.33%)(P<0.05). There was no significant difference in the incidence of drug-related adverse reactions between the two groups during the treatment period. Conclusion The application of latamoxet in the treatment of lobar pneumonia can significantly improve the clinical efficacy of patients, and is conducive to the protection of their prognosis and quality of life.

Effect and prognosis of treatment of lobar pneumonia with latamoxet / 中国生化药物杂志

Objective To investigate the therapeutic effect of cefradine on lobar pneumonia and its influence on the prognosis of patients with lobar pneumonia. Methods 90 cases of lobar pneumonia patients from December 2015 to May 2017 were randomly divided into the study group and the control group, with 45 cases in each group. The study group was treated with latamoxef on the basis of routine treatment, the control group was treated with cefoperazone on the basis of routine treatment ,recorded in two groups after 2 weeks of treatment. The clinical efficacy,drug related adverse reactions occur of the two groups were recorded after two weeks of treatment. Results The total effective rate in the study group(93.33%) was significantly higher than that of the control group(73.33%)(P<0.05). There was no significant difference in the incidence of drug-related adverse reactions between the two groups during the treatment period. Conclusion The application of latamoxet in the treatment of lobar pneumonia can significantly improve the clinical efficacy of patients, and is conducive to the protection of their prognosis and quality of life.