Study on French medical insurance payment policy for innovative medical products paid under DRG / 中国药房

OBJECTIVE To analyze the implementation experience of France’s additional list system for innovative medical products， and to provide reference for China to support medical institutions to use innovative medical products. METHODS Taking France as a case study， using policy analysis method， this paper systematically studied the practice of establishing additional list system to compensate for innovative medical products in France under diagnosis-related group （DRG） payment， including the establishment background， selection procedure and implementation effect. The suggestions were provided on the medical insurance payment methods for innovative medical products in China. RESULTS & CONCLUSIONS The additional list system established a compensation and payment system for innovative medical products with significant clinical efficacy but high treatment cost， covering four stages： application， evaluation， payment and adjustment， which effectively reduced the drug burden on medical institutions， promoted the use of innovative pharmaceutical products by medical institutions， and stimulated the innovation drive of the pharmaceutical industry， but at the same time brought payment pressure to the medical insurance fund. With the rapid spread of our DRG/diagnosis-intervention packet payment reform of China， some regions have also explored the establishment of a compensation and payment mechanism for innovative medical products， but there are still imperfections. We can refer to the implementation experience of the French additional list system and establish an effective compensation and payment system for innovative medical products starting from the establishment of selection criteria， the selection of compensation mode and the implementation of dynamic adjustment.

Monitoring of foodborne pathogens in some ready-to-eat fruits and vegetables in Shanghai in 2021 / 上海预防医学

ObjectiveThe contamination of foodborne pathogens in ready-to-eat fruits and vegetables in Shanghai was analyzed to provide a scientific basis for food safety， risk assessment and related supervision. MethodsFrom June to September 2021， a total of 143 batches of12 kinds of ready-to-eat fruits and vegetables such as lettuce， chicory， and cherry tomatoes were collected from farmers’ markets， supermarkets， and e-commerce platforms. The total number of bacterial colonies， Salmonella， Listeria monocytogenes， Staphylococcus aureus， Cronobacter spp. and Shiga toxin-producing Escherichia coli in the samples were tested according to National Food Contamination and Harmfulness Risk Monitoring Manual. ResultsAmong the 143 batches， foodborne pathogens were detected in 68 batches， with a total detection rate of 47.55% （68/143）. A total of 79 strains of foodborne pathogens were detected. The detection rate of Staphylococcus aureus was the highest （32.87%， 47/143）， followed by Cronobacter spp. （20.98%， 30/143）， Salmonella （0.70%， 1/143）， Listeria monocytogenes （0.70%， 1/143）， Shiga toxin-producing Escherichia coli （0.00%）. Furthermore， the detection rate was higher in different ready-to-eat fruits and vegetables： chicory （17.33%）， cucumber （17.14%）， cherry tomatoes （16.00%）， and honeydew melon （15.38%）， respectively. Meanwhile， the contamination rate of pathogens in ready-to-eat fruits and vegetables from farmers’ markets， supermarkets， and e-commerce platforms was relatively high. ConclusionReady-to-eat fruits and vegetables in Shanghai are contaminated by foodborne pathogens. The prevention and control of the contamination of post-harvest fruits and vegetables should be strengthened to reduce the risk of foodborne disease outbreaks.

Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.

Clinical and molecular characteristics of a family with familial hypercholesterolemia with LDLRAP1 and ABCG8 gene abnormality / 中华检验医学杂志

Objective:To study the clinical and molecular characteristics of a family with familial hypercholesterolemia (FH) with LDLRAP1 and ABCG8 gene abnormality.Methods:In September 2020, one case of FH was included in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; peripheral venous blood samples of members of the family were collected to detect serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) indicators; use high-performance liquid chromatography to detect serum stigmasterol and sitosterol content; perform second-generation gene sequencing to detect gene mutations in probands and family members; use Pymol software to detect gene mutations point for pathogenicity analysis, and use Uniprot Modelling software to perform protein structure modeling.Results:The patient presented with anemia, multiple xanthomas and early-onset acute coronary syndrome. The coronary angiography showed severe coronary artery lesions; abdominal ultrasound showed splenomegaly; blood smear showed shaped erythrocytes and large platelets. The level of serum TC, LDL-C, stigmasterol and sitosterol was 8.54 mmol/L (2.3-5.7 mmol/L), 4.84 mmol/L (range of normal value 1.3-4.3 mmol/L), 44 μmol/L (1.0-10 μmol/L), 28 μmol/L (1.0-15 μmol/L), respectively; LDLRAP1 gene mutation was found: exon4 c.415C>T:p.Q139X; the truncated protein formed by this homozygous mutation lost multiple stable protein structure regions, which can not have a normal function. At the same time, ABCG8 gene mutations were also found: exon13 c.1895T>C (p.V632A) and exon8 c.1199C>A:p.T400K . Two cases of family members had a mild increase in HDL-C (Ⅱ5: 2.33 mmol/L, Ⅱ6∶2.96 mmol/L), 3 cases carrying the ABCG8 gene mutations had a slight increase in stigmasterol (Ⅱ8: 23 μmol/L, Ⅱ7: 24 μmol/L, Ⅰ2: 18 μmol/L) and sitosterol (Ⅱ8: 41 μmol/L, Ⅱ7: 33 μmol/L, Ⅰ2: 45 μmol/L), suggesting that its association with the concentration of plant sterols. Conclusions:FH patients with LDLRAP1 and ABCG8 gene abnormalities may have abnormal plant sterol concentrations, and their clinical manifestations are more complicated. Therefore, family history, LDL-C, plant sterol levels, and genetic test results should be considered comprehensively.

Inspiration from International Experience on Risk Sharing Agreements of Medical Insurance Access for CAR-T Products / 中国药房

OBJECTIVE：To learn from the experience of foreign listed chimeric antigen receptor T lymphocyte （CAR-T） products in signing risk sharing agreements in medical insurance access ，so as to provide references for relevant decisions of medical insurance departments in China. METHODS ：Taking 9 risk sharing agreements of CAR-T products marketed in the United Kingdom，France，Italy and Germany as samples ，the international experience of medical insurance payment of CAR-T products were analyzed from six dimensions ，such as agreement types ，monitoring indicators ，data collection metho ds，agreement periods ， payment conditions and payment methods. Some suggestions were put forward for the medical insurance access of these products in China. RESULTS & CONCLUSIONS ：Four sample countries generally signed risk sharing agreements of medical insurance access （financial agreement and performance-based agreement ）with pharmaceutical enterprises ；the indicators such as progressive disease and progression-free survival were collected by using data collection system or clinical research data ，so as to monitor the efficacy and safety of CAR-T products. The agreement periods and payment conditions were determined according to different agreement types；“medical insurance advance payment ”or“pharmaceutical enterprise advance payment ”combined with “staged payments ” were adopted for risk control. Solving the risk of medical insurance funds caused by “efficacy uncertainty ”is the core issue of CAR-T product access. The induction of risk sharing agreements may be the way to solve this problem ，and the scientific design of the various elements of risk sharing agreements is a prerequisite to ensure that the agreement is operational.

Single-nucleus transcriptomic landscape of primate hippocampal aging

The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing. Here, we reported a variety of new aging-associated phenotypic changes of the primate hippocampus. These include, in particular, increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. To understand their cellular and molecular causes, we established the first single-nucleus transcriptomic atlas of primate hippocampal aging. Among the 12 identified cell types, neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging. In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis. This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases.

Advances in research on etiology, diagnosis and treatment of non-obstructive myocardial infarction / 中国医师杂志

Myocardial infarction refers to severe coronary artery stenosis, which leads to continuous and complete occlusion of coronary artery and myocardial necrosis. Coronary artery stenosis (>50%) or occlusion can be seen in 90% of patients undergoing coronary angiography, but 10% of patients have no obvious stenosis, that is, non obstructive myocardial infarction (MINOCA). The incidence rate of MINOCA was about 6%, showing an upward trend year by year, with an average age of 55 years, of which 40% of women. Its etiology is complex, the onset is urgent, and the clinical manifestations are complex and changeable. The incidence of major adverse cardiovascular events (MACE) is very high, and the mortality rate within one year is as high as 3.5%. There is no unified diagnosis and treatment plan at present. In this paper, the etiology, diagnosis and treatment of MINOCA were reviewed.

Efficacy analysis of decitabine monotherapy or combined with arsenic trioxide in treatment of myelodysplastic syndromes / 白血病·淋巴瘤

Objective To analyze the therapeutic effect and tolerability of decitabine monotherapy or combined with arsenic trioxide for the treatment of patients with myelodysplastic syndromes (MDS). Methods Clinical characteristics of 32 patients with primary MDS in North Hospital of Ruijin Hospital Affiliated to Medical College of Shanghai Jiaotong University from January 2014 to April 2017 were retrospectively analyzed. The clinical data of these patients were collected, and the patients were followed up. Decitabine combined with arsenic trioxide was used in 23 cases, decitabine (20 mg·m-·2d-1) and arsenic trioxide (0.16 mg/kg) were administrated from day 1 to day 5 and was repeated every 4-6 weeks. For the remaining 9 cases, only decitabine was applied, decitabine(20 mg·m-2·d-1) was administrated from day 1 to day 5 and was repeated every 4-6 weeks. The clinicopathological characteristics and the effect of genetic mutations on the efficacy of treatment were investigated. Results Of the 32 patients with primary MDS, 18 were male and 14 were female. The patients were 17-72 years old with a median age of 56 years old. Genetic analysis revealed 10 cases with TP53 mutations, 8 cases with TET2 mutations, 4 cases with U2AF1 mutations, 3 cases with RUNX1 mutations, 3 cases with ASXL1 mutations, 2 cases with NRAS mutations, 2 cases with DNMT3A mutations and 1 case with JAK2 V617 mutation. The follow﹣up time was 2-23 months with a median follow﹣up time of 8 months. A total of 21 cases (65.6%) attained treatment response. Among them, there were 10 cases (31.3%) with complete remission (CR), 5 cases (15.6%) with bone marrow complete remission (MCR), and 6 cases (18.7%) with hematological improvement. There was no significant difference in the efficiency and CR rate between the combination group and the monotherapy group (P＝0.441, P＝0.681). Ten cases were found to have TP53 mutations, of which 7 cases had CR. Multivariate analysis demonstrated that TP53 mutation was an independent risk factor for CR (P＝ 0.037). All patients developed myelosuppression after treatment, of which 16 cases developed pulmonary infection. Conclusions Decitabine combined with arsenic trioxide in the treatment of MDS is effective and well tolerated. The therapeutic effects of decitabine monotherapy or decitabine combined with arsenic trioxide for treatment of patients with TP53 mutations are better than the average levels.

Bibliometric analysis on research hotspots on HIV post-exposure prophylaxis related articles in the world, 2000-2017 / 中华流行病学杂志

Objective To analyze and reveal the distribution,research hotspots and study trend of worldwide published articles correlated with HIV/AIDS post-exposure prophylaxis (PEP),and provide information for related studies in China.Methods CiteSpace software 5.1 was used to visualize all related papers in the web of science database published during 2000-2017.Results The average growth rate of international PEP-related papers was 10.78％,and number of published papers in 2016 was highest (n=34),relevant research hotspots have shifted from the prevention of occupational HIV exposure to the prevention of non-occupational HIV exposure in group at high risk,such as MSM,in recent years.Clustering analysis classified research hotspots into three categories,including risk reduction through enhanced intervention,current status of global HIV PEP and German-Austrian Recommendation.Conclusions Non-occupational HIV PEP in groups at high-risk,especially MSM,has received increasing attention in recent years,the research of PEP mainly focus on improving the awareness and use of PEP in MSM and compliance in the course of medication.In the context of severe HIV epidemic in MSM without effective control in China,PEP should be strengthened to assess and explore the risk of HIV infection in MSM to provide reference for medical personnel and related departments to implement HIV non-occupation exposure blockade and formulate PEP medication.

The study of the relapsed patients with major depressive disorder based on spectral dynamic causal modeling / 实用放射学杂志

Objective To explore the effects of abnormal effective connectivity within the default mode network (DMN)in relapsed patients with major depressive disorder.Methods Resting-state functional magnetic resonance imaging (rs-fMRI)data were collected from 21 patients of first-episode depression and 16 patients with relapsed depression,and 37 matched healthy controls.The effective connectivity within the DMN was investigated with spectral dynamic causal modeling (spDCM)method.Results spDCM analysis showed that the effective connections from left parietal cortex(LPC)to right parietal cortex(RPC)and medial frontal cortex(mPFC)were significantly decreased,while the connection from posterior cingulate cortex(PCC)to mPFC was increased in patients of first episode depression compared to healthy controls.Furthermore,the connectivity between mPFC and LPC were enhanced in patients with recurrent depression compared withhealthy control subjects,as well as PCC.Meanwhile,the connectivity between mPFC and PCC was enhanced in patients with relapse depression compared with patients of first episode depression.Conclusion Both first-episode and relapsed patients demonstrated abnormal effective connectivity of LPC,implicating that abnormal LPC connectivity may be associated with the neural substrates of depression.In contrast,the patients with relapsed depression showed aberrant connectivity with the mPFC,suggesting that abnormal effective connectivity of the mPFC may play an important role in the relapse of depression.

Effects of the abnormalities in functional connectivity of the affective network on the relapse of major depressive disorder / 实用放射学杂志

Objective To explore abnormalities in functional connectivity of the affective network (AN) in relapse of major depressive disorder (MDD) after antidepressant treatment combined with resting state functional connectivity analysis.Methods Eleven recurrent MDD subjects after treatment,seventeen non recurrent MDD subjects after treatment and seventy-two healthy controls underwent fMRI scan.The amygdala,the pallidum,the insular cortex and the anterior cingulate cortex of the AN were selected as the template.Group independent component analysis (ICA) was performed to decompose the fMRI images into spatially independent components and the independent component which fit this template best was selected as AN.Two-sample t-tests were performed to investigate the changes in functional connectivity of the AN.Finally,the right amygdala and the medial prefrontal cortex were defined as seed regions.Results Compared with healthy control subjects and non-recurrent MDD group,recurrent MDD group showed significantly increased functional connectivity in the right amygdala in AN(P＜0.001).Meanwhile,the functional connectivity between the right amygdala and the medial prefrontal cortex was significantly decreased in recurrent MDD group(P ＜0.05).Conclusion Abnormal resting-state functional connectivity of the right amygdala after antidepressant treatment in MDD was found,suggesting that altered amygdala functional connectivity may serve as a predicator of relapse of the MDD.

Bibliometric analysis on research hotspots on HIV post-exposure prophylaxis related articles in the world, 2000-2017 / 中华流行病学杂志

Objective To analyze and reveal the distribution,research hotspots and study trend of worldwide published articles correlated with HIV/AIDS post-exposure prophylaxis (PEP),and provide information for related studies in China.Methods CiteSpace software 5.1 was used to visualize all related papers in the web of science database published during 2000-2017.Results The average growth rate of international PEP-related papers was 10.78％,and number of published papers in 2016 was highest (n=34),relevant research hotspots have shifted from the prevention of occupational HIV exposure to the prevention of non-occupational HIV exposure in group at high risk,such as MSM,in recent years.Clustering analysis classified research hotspots into three categories,including risk reduction through enhanced intervention,current status of global HIV PEP and German-Austrian Recommendation.Conclusions Non-occupational HIV PEP in groups at high-risk,especially MSM,has received increasing attention in recent years,the research of PEP mainly focus on improving the awareness and use of PEP in MSM and compliance in the course of medication.In the context of severe HIV epidemic in MSM without effective control in China,PEP should be strengthened to assess and explore the risk of HIV infection in MSM to provide reference for medical personnel and related departments to implement HIV non-occupation exposure blockade and formulate PEP medication.

Research development of human infection with H5N6 avian influenza virus / 军事医学

Avian influenza virus is a new recombinant virus , which can cause severe respiratory symptoms ,such as short course,acute disease,and a high mortality rate.The purpose of this paper was to summarize the current status of this virus in terms of its epidemiology ,genetic evolution and virulence .By introducing the advancement in the research of this subtype virus, we hope to provide data and evidence ,for effective surveillance and prevention of this virus .

Design, synthesis and anti-platelet aggregation activities of ligustrazine-tetrahydroisoquinoline derivatives / 药学学报

Abstract: Fifteen novel ligustrazine-tetrahydroisoquinoline derivatives were designed and synthesized according to the association principle of pharmaceutical chemistry. The structures were identified by IR, NMR and ESI-MS. The inhibitory activities of platelet aggregation induced by ADP and AA have been measured by Bron method. Preliminary pharmacological results showed that compounds 7g, 7h and 7n had potent inhibitory activity against platelet aggregation induced by AA, and the compound 7o showed significant inhibitory activity against platelet aggregation induced by ADP.

The relationship between serum cystatin C concentration and the severity of ACS patients with lesions degree and PCI treatment prognosis / 国际检验医学杂志

Objective To explore the relationship between serum cystatin C concentration and severity of coronary artery disease and prognosis after peripheval component interconnet(PCI)treatment.Methods 352 patients diagnosed as ACS and received PCI treatment successfully were enrolled in the study as ACS group.In addition to that,60 people who underwent coronary angiography and the test results was good were recruited as control group.The serum lipids,cystatin C concentrations were tested,and the rela-tionship between the number of coronary lesions,Gensini score and cystatin C concentrations were analyzed.The risks of major car-diovascular events in different cystatin C concentration groups were analyzed.Results Cystatin C concentrations of ACS group were significant higher than control group (P <0.05).Cystatin C concentrations were significantly different among patients with different number of diseased branches(P <0.05).The patients with higher number of diseased branches were with higher concen-tration of cystatin C.There was a positive correlation between cystatin C concentration and Gensini score (r=0.84,P <0.05).The risk of major cardiovascular events in high cystatin C concentration group within 1 year after PCI treatment increased significantly compared with control group,the OR values were 16.63(95%CI :3.87-71.49,P <0.05).Conclusion Cystatin C correlated with the severity of coronary artery disease and the occurrence of major cardiovascular events within one year after PCI treatment.

Design, synthesis and antitumor activity of valproic acid salicylanilide esters / 药学学报

A series of valproic acid salicylanilide esters were designed and synthesized based on the principle of prodrug. The structures of the target compounds were confirmed by MS, 1H NMR and 13C NMR. Anti-tumor activities of these compounds against K562, A549, A431 cells in vitro were investigated by MTT assay and SRB assay. The results indicated that the compounds 6h-6j were found to have stronger cell growth inhibitory action than gefitinib, and comparable to niclosamide, which are worth to be intensively studied further.

Design, synthesis and Na+/H+ exchanger isoform-1 inhibitory activity of feruloylagmatine analogues / 药学学报

In order to search for novel inhibitors of Na+/H+ exchanger isoform-1 (NHE-1), nine feruloylagmatine analogues were designed and synthesized from ferulic acid and agmatine. The structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR and mass spectra, among which compounds 5f-5i were novel compounds. The results of preliminary pharmacological test showed that some of the compounds possessed strong NHE-1 inhibitory activity, among which compounds 5a, 5b and 6c were more potent than cariporide in NHE-1 inhibition.

Synthesis of ferulic acid derivatives and their inhibitory effect on platelet aggregation / 药学学报

Ferulic acid, an useful compound of Chinese traditional medicine, was used as leading compound. Six ferulic acid derivatives were designed and synthesized based on bioisosterism. Their structures were characterized by IR, 1H NMR, 13C NMR and mass spectra. In vivo experiment showed that ferulic acid derivatives had good inhibitory effects on adenosine diphosphate (ADP) induced platelet aggregation, which were significantly higher than that of Ozagrel.