Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

OBJECTIVE: The medicinal mushroom Sanghuangporus vaninii produces pharmaceutically valuable hispidin polyphenols in natural habitats. However, due to the slow growth in nature, S. vaninii grown in the field (sclerotia) is not reliable for pharmaceutical purposes. Although higher biomass of fungal mycelia can be obtained in submerged cultures, the accumulation of hispidin polyphenols is rare. METHODS: In this study, the polyunsaturated fatty acids (PUFAs), linoleic acid (LA), linolenic acid (ALA), and methyl jasmonate (MeJa) were employed as the stimulant agents to coordinate the accumulation of biomass and hispidin polyphenols in its submerged cultures. RESULTS: The addition of LA and ALA promoted the mycelial accumulation, while the addition of MeJa inhibited the growth of S. vaninii concomitant with reduced total polyphenols. UPLC-Triple-TOF-MS analysis revealed an increased production of hispidin, phellinstatin, pinnilidine, and its derivatives upon the addition of LA and ALA, and hypholomine B and its isomer, 3,14'-bihispidinyl, and phelligridin E upon the addition of MeJa on day 13. Intriguingly, total polyphenols from the MeJa-supplementing cultures harbored a high capacity in scavenging free radicals. Chemical structural analysis showed that hispidin polyphenols had higher antioxidant activity due to more hispidin moieties induced by MeJa. CONCLUSION The supplement of PUFAs affects the synthesis and composition of hispidin polyphenols in S. vaninii. Our results provide a possibility to coordinate the production of hispidin polyphenols via submerged cultures of S. vaninii.

Objective:To screen plasma exosomal protein molecular markers in patients with spinal cord injury (SCI) by applying Label-Free quantification and bioinformatics analysis.Methods:Fifty plasma specimens from the First Affiliated Hospital of Nanjing Medical University (from January 2021 to June 2022) were collected from SCI patients and healthy people, respectively. Plasma exosomes were isolated using ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis and western blot. Plasma exosomal differentially expressed proteins (DEPs) were analyzed using Label-Free quantitative proteomics, and DEPs were characterized, annotated, and enriched based on Gene Ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) databases. The screened DEPs were validated by western blot and enzyme linked immunosorbent assay (ELISA) using plasma exosomal specimens.Results:According to the spinal cord injury classification of the American Spinal Injury Association, 14 cases were grade A, 19 cases were grade B, 12 cases were grade C, and 5 cases were grade D. Plasma exosomes of SCI patients and control groups showed typical cup-like morphology, with diameters mainly ranging from 30-200 nm. A total of 493 exosomal proteins were identified by Label-Free quantification, and 126 proteins were screened for differential expression, of which 38 were up-regulated and 88 were down-regulated. GO annotation revealed that DEPs were mainly involved in functions such as protein activation cascade, complement activation and immune response. KEGG pathway analysis revealed that DEPs were involved in biological pathways such as complement and coagulation cascade reactions, proteasome and neurodegenerative disease pathways. Two candidate proteins, APOB and S100A9, were initially screened based on quantitative results from proteomics and bioinformatics analyses. Western blot results showed that the relative expression of S100A9 protein in plasma exosomes of 30 SCI patients (1.62±0.19) was elevated compared with that of 30 control groups (0.86±0.24), and the difference was statistically significant ( t=8.55, P<0.001), while the relative expression of APOB protein (1.06±0.13 and 1.02±0.23) were not statistically significant ( t=0.46, P=0.653). The results of ELISA analysis showed that the expression of S100A9 in plasma exosomes of patients with different degrees of SCI (grade A 197.7±11.7 pg/ml, grade B 151.7±15.2 pg/ml, grade C 136.3±14.7 pg/ml) had statistical significance ( F=69.94, P<0.001), the higher the severity of SCI, the higher the expression of S100A9 in plasma exosomes (A vs. B, q=13.11, P<0.001; A vs. C, q=15.66, P<0.001; B vs. C, q=4.19, P=0.005). Conclusion:S100A9 is a potentially valid plasma exosomal molecular marker for assessing the severity of SCI.

Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.

Objectives:To explore health-related quality of life (HRQoL) and identify its associated variables in Chinese patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to adult patients with MPNs to assess symptom burden measured by MPN-10 and HRQoL measured by Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) .Results:The data from 1405 respondents with MPNs, including 645 (45.9%) with essential thrombocythemia (ET) , 297 (21.1%) with polycythemia vera (PV) , and 463 (33.0%) with myelofibrosis (MF) , were analyzed. 646 (46.0%) respondents were male. The median age was 56 (range, 18-99) years. The mean MPN-10 scores were 13.0±12.7, 15.0±14.7, and 21.0±16.6 ( P<0.001) , and the physical component summary (PCS) and mental component summary (MCS) scores were 48.0±8.5, 47.0±9.0, and 42.0±10.0 ( P<0.001) and 51.0±11.0, 50.0±10.8, and 49.0±11.1 ( P=0.002) for respondents with ET, PV, and MF, respectively. Respondents with MF reported the lowest score of physical functioning, role functioning, emotional functioning, cognitive functioning, social function, and global health status (all P<0.01) and the highest score of fatigue, pain, dyspnea, appetite loss, diarrhea, and financial problems (all P<0.05) in EORTC QLQ-C30. Multivariate analyses revealed that higher MPN-10 scores were significantly associated with lower PCS (-0.220 to -0.277, P<0.001) and MCS (-0.244 to -0.329, P<0.001) scores; increasing age (-1.923 to -4.869; all P<0.05) , lower PCS score. Additionally, comorbidity (ies) , symptom at diagnosis, splenomegaly, anemia, unknown driver gene, and higher annual out-of-pocket cost were significantly associated with lower PCS and/or MCS scores. However, age ≥ 60 years, urban household registration, concomitant medication, and receiving ruxolitinib therapy in respondents with MF were associated with higher MCS scores. Weak correlations were found between MPN-10 score (except the subscale of appetite loss and constipation) and EORTC QLQ-C30 score in majority of subscales in respondents with ET (| r| = 0.193-0.457, all P<0.001) , PV (| r| = 0.192-0.529, all P<0.01) , and MF (| r| = 0.180-0.488, all P<0.001) , respectively. Conclusions:HRQoL in patients with MPN was significantly reduced, especially in patients with MF. Sociodemographic and clinical variables were significantly associated with the HRQoL in patients with MPNs.

Objective:To compare the effects of paliperidone palmitate and olanzapine in the treatment of schizophrenia and its influence on the metabolism of patients.Methods:From February 2017 to February 2019, 86 patients with schizophrenia admitted to the Second People's Hospital of Taizhou were divided into observation group(43 cases) and control group(43 cases) according to random number table method.The observation group was injected paliperidone palmitate into deltoid muscle, while the control group was given olanzapine orally.Both two groups were treated for 12 weeks.The changes of PANSS and CGI scores, body mass, glucose metabolism, lipid metabolism and serum prolactin were compared between the two groups before and after treatment.Results:Before treatment, there were no statistically significant differences in the PANSS score, CGI score, body mass, glucose metabolism, lipid metabolism and serum prolactin between the two groups(all P>0.05). After treatment, the PANSS score and CGI score in the control group were (37.25±3.78)points and (2.51±0.36)points, respectively, which in the observation group were (37.28±4.35)points and (2.63±0.43)points, respectively, which were lower than before treatment(control group: t=29.010 and 11.817, observation group: t=36.257 and 13.503, all P<0.05), there were no statistically significant differences between the two groups(all P>0.05). After treatment, the body weight of the observation group was (62.18±3.56)kg, which was lower than that of the control group[(68.27±4.35)kg] ( t=7.105, P<0.05). After treatment, the fasting blood glucose(FBG) and HbA1c of the control group were (5.91±0.27)mmol/L, (8.94±0.78)%, respectively, which were higher than those of the observation group [(5.39±0.34)mmol/L and (7.65±0.63)%] ( t=7.854, 8.437, all P<0.05). The levels of TC, LDL-C and TG in the control group were (4.27±0.42)mmol/L, (3.27±0.43)mmol/L, (1.87±0.28)mmol/L, respectively, which in the observation group were (3.54±0.48)mmol/L, (2.56±0.54)mmol/L, (1.35±0.36)mmol/L, respectively, the differences were statistically significant between the two groups ( t=7.505, 6.745, 7.477, all P<0.05). After treatment, the serum level of prolactin of the control group was (84.35±12.41)μg/L, which was higher than that of the observation group [(59.87±9.53)μg/L]( t=10.259, P<0.05). Conclusion:Paliperidone palmitate is as effective as olanzapine in the treatment of schizophrenia, but it has little effect on body weight, glucose metabolism, lipid metabolism and prolactin level.

Objective:To analyze the trend of smoking prevalence and its risk factors among adults in Shaanxi province from 2007 to 2015.Methods:We used data from China Chronic Disease and Risk Factor Surveillance in 2007, 2010, 2013 and 2015. The current smoking prevalence and trends of the four surveys were calculated. Its risk factors were analyzed by multivariate logistic regression from each survey and then from all pooled data of the three surveys.Results:The number of participants in 2007, 2010, 2013 and 2015 was 1 542, 3 000, 10 166 and 6 330, respectively. The current smoking prevalence dropped from 34.34 % in 2007 to 26.22 % in 2013, but increased to 28.33 % in 2015 (trend χ2 test: Z=2.53, P=0.01). The results from four pooled data showed that the current smoking prevalence of men was higher than that of women ( OR=75.03, 95 %CI: 63.57-88.55). The current smoking prevalence of people aged 45-59 was higher than that of people aged 18-44 ( OR=1.28, 95 %CI: 1.15-1.41). In addition, the current smoking prevalence of those who were educated for 7-9 years and more than 9 years were higher than those who were educated for less than 6 years (people with education for 7-9 years OR=1.44, 95 %CI: 1.29-1.61; people with education >9 years OR=1.43, 95 %CI: 1.26-1.63). The current smoking prevalence of the single was lower than those of married/cohabitants ( OR=0.54, 95 %CI: 0.37-0.77). The current smoking prevalence of retirees were lower than those of employees ( OR=0.46, 95 %CI: 0.38-0.57) and smoking prevalence of alcohol drinkers were higher than those of non-drinkers ( OR=2.92, 95 %CI: 2.67-3.19). Conclusion:From 2007 to 2015, the current smoking prevalence of Shaanxi population was high and the trends remained stable. It is necessary to strengthen smoking control and health education for men, people over 45 years old, people with education level 7 years and above, and working personnel in Shaanxi province.

Objective To study the correlation between characteristic parameters of photoplethysmography( PPG)and severity of coronary artery lesions.Methods Two hundred and twenty-six CHD patients who underwent CAG in our hospital from August 2018to November 2018were divided into single-vessel lesion group(n=55),double-vessel lesion group(n=74)and multi-vessel lesion group(n=97)according to their CAG.Their stiffness index(SI),crest time(CT),normalized crest time(NCT)and crest time ratio(CTR)were recorded by PPG and analyzed by correlation analysis.Results The SI was significantly different in single-vessel lesion group,double-vessel lesion group and multi-vessel lesion group(6.479±0.819m/s,6.692±1.051m/s and 6.943±1.096m/s,P=0.024).No significant difference was detected in CT,NCT and CTR among single-vessel lesion group,double-vessel lesion group and multi-vessel lesion group(P＞0.05).The SI was positively correlated with the severity of coronary artery lesions(r=0.162,P=0.015).Conclusion The SI is correlated with the severity of coronary artery lesions,which is of a certain value in predicting the severity of coronary artery lesions.

Objective: To explore the prevalence of chronic diseases and related risk factors in Shaanxi province. Methods: Multi-stage stratified cluster random sampling was used to collect the sample from permanent residents in 10 national surveillance points in Shaanxi province in 2015. Behavioral risk factors (smoking, drinking, diet and physical activity) were investigated by face-to-face interviews and biological risk factors (BMI, blood pressure, blood glucose and blood lipid) were collected by physical measurements and laboratory tests. Designed weight, no response weight and post hierarchical weight were taken into account in the data analysis. Binary logistic regression models were used to examine the pair-wise associations among 8 risk factors. Results: A total of 6 174 persons were included in the analysis. The following weighted prevalence were noticed in Shaanxi province in 2015, that including current smoking as 28.19%, harmful use of alcohol as 6.20%, inadequate intake of vegetables and fruits as 55.62%, physical inactivity as 19.56%, overweight and obesity as 46.82%, hypertension as 31.12%, raised fasting blood glucose as 4.27%, and raised total cholesterol as 20.96%. Eight risk factors were found to be associated with each other. The mean numbers of risk factors were 2.41 per male and 1.85 per female, 1.94 per urban resident and 2.28 per rural resident. Conclusions Risk factors for chronic diseases among adults aged 18 or older were more than the national levels in Shaanxi province in 2015. Male and rural residents presented more risk factors than their counterparts. Correlations between risk factors implied that a combined package of interventions was needed to reduce these risk factors.

OBJECTIVE:To adopt SIMPLE pharmaceutical care mode in chronic disease management of bronchial asthma and COPD patients,and to evaluateits the effect. METHODS:By random sampling,a total of 200 bronchial asthma and COPD patientsselected from respiration department in the First Affiliated Hospital of Soochow University during Sept. 2016-Jun. 2017 were divided into control group(100 cases)and intervention group(100 cases)by simple randomization. Control group received routine treatment. Intervention group additionally received education on quitting smoking,effective use of the inhaler,monitoring detection indexes, selecting drugs correctly,scientific life style. Inhaled device scores,lung function indexes (FEV1％,FEV1/FVC),the number of patients with acute attack/exacerbation,clinical effective control rates,ADR occurrence rates,compliance of using apparatus(MMAS-8 score)were compared between 2 groups before enrollment,3 and 6 months after enrollment. RESULTS:Commpared with during enrollment,inhaled device score,clinical effective control rate and MMAS-8 score of intervention group incereased significantly 3,6 months after enrollment,while patients with acute attack/exacerbation ≥2 times decreased significantly,with statistical significance (P<0.05). Compared with control group,inhaled device score,clinical effective control rate,MMAS-8 score and FEV1％ of intervention group increased significantly,patients with acute attack/exacerbation ≥2 times decreased significantly 3 and 6 months after enrollment with statistical significance (P<0.05);the ADR occurrence rate was lower than control group,with statistical significance (P<0.05). CONCLUSIONS:Chronic disease management of bronchial asthma and COPD patients with SIMPLE pharmaceutical care mode can improve medication compliance and clinical efficacy,and reduce ADR.