BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

Objective To observe the effect of Qixian Tongluo Formula on contralateral corticospinal tract(CST)remodeling and motor functional recovery in rats with cerebral infarction,and to explore its potential molecular mechanism from the perspective of regulating factors related to never remodeling.Methods The rat middle cerebral artery occlusion(MCAO)model was established by silk thread ligation.Fifty model rats were randomly divided into model group,citicoline group(0.054 g·kg-1),Qixian Tongluo Formula low-,medium-and high-dose(7.83,15.66,31.32 g·kg-1)groups,and sham operation group,with 10 rats in each group.The intervention administration was started on the 3rd day after operation once a day for 26 consecutive days.On the 3rd,14th and 28th day after operation,the gross motor function was evaluated by Longa score,and the fine motor function was evaluated by beam-walking test(BWT)score.The contralateral motor cortex was injected with the nerve tracer biotin dextran amine(BDA)on the 14 th day after operation to anterogradely trace the CST.On the 28th day after operation,the expression of axonal growth associated protein-43(GAP-43)and BDA positive fibers in the contralateral motor cortex and cervical spinal cord were detected by immunohistochemistry.The co-localization areas of BDA positive fibers and presynaptic marker protein vesicular glutamate transporter 1(VGLUT1)in the cervical spinal cord gray matter were detected by immunofluorescence.The expressions of brain-derived neurotrophic factor(BDNF),glial cell-derived neurotrophic factor(GDNF),nerve growth factor(NGF)and nerve remodeling-associated inhibitory factor[Nogo-A,oligodendrocyte myelin glycoprotein(OMgp)and myelin-associated glycoprotein(MAG)]in the contralateral motor cortex were detected by Western Blot.Pearson correlation analysis was used to analyze the correlation between Longa score or BWT score and BDA/VGLUT1 co-localization area,respectively.Results Compared with the sham operation group,rats in the model group had obvious symptoms of motor function deficits,and the Longa scores were significantly increased(P＜0.01)and the BWT scores were significantly decreased(P＜0.05,P＜0.01)at each time point.The expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was up-regulated(P＜0.05),the number of edge-crossing fibers from the posterior funiculus in cervical cord was increased(P＜0.05),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was increased(P＜0.05),the expressions of BDNF,GDNF and NGF in the contralateral motor cortex were up-regulated(P＜0.05),while the expressions of Nogo-A,OMgp and MAG were down-regulated(P＜0.05).Compared with the model group,the Longa scores in each administration group on the 14th and 28th day after MCAO operation were significantly decreased(P＜0.01),the BWT scores were significantly increased(P＜0.01),the expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was significantly up-regulated(P＜0.01).The number of edge-crossing fibers from the posterior funiculus in cervical cord was significantly increased(P＜0.01),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was significantly increased(P＜0.01).The expressions of BDNF,GDNF and NGF in the contralateral motor cortex were significantly up-regulated(P＜0.01,P＜0.05),while the expressions of Nogo-A,OMgp and MAG were significantly down-regulated(P＜0.05),and the most significant effect was observed in the high dose group.The Longa score was negatively correlated with the co-localization area of BDA/VGLUT1(r=-0.89,P＜0.01),and the BWT score was positively correlated with the co-localization area of BDA/VGLUT1(r=0.84,P＜0.01).Conclusion Qixian Tongluo Formula can improve motor function through promoting contralateral CST remodeling in MCAO rats after cerebral infarction,and the molecular mechanism may be related to the regulation of the expression of nerve remodeling-associated factor in the contralateral motor cortex.

Chronic myeloid leukemia(CML)is a hematological system malignant tumor characterized by the appearance of Ph chromosomes and the formation of BCR-ABL fusion gene.With the emergence of tyrosine kinase inhibitors,the efficacy and survival of CML have been improved significantly.However,there are still some patients with inevitable disease progression and recurrence.In CML patients,the body's own an-ti-tumor immunity can play a role in monitoring,recognizing and eliminating the leukemia cells,which is closely correlated with the occurrence,development,curative efficacy and prognosis of the disease.The immune cells such as natural killer(NK)cells,T cells,dendritic cells,Treg and MDSC play a key role in anti-tumor immunity.Therefore,this article reviews the characteristics of CML immune cells,correlation between the body's own anti-tumor immune status and therapeutic effect,and the recent progress of CML immunotherapy.

The construction of "New Medicine" is the leader of the innovative development of medical education in China in the new era. Strengthening the cross-integration of medicine and science is helpful to promote the training of top-notch interdisciplinary innovative talents under the multidisciplinary background of "Medicine + X". The applied psychology major in medical colleges has unique advantages in education and teaching resources. How to combine the advantages to construct the education model of the integration of medicine and science is still in the exploration stage. This paper analyzes the current situation of talent training of the applied psychology major in medical colleges and the new requirements for discipline-major construction under the background of "New Medicine" construction, demonstrates the measures to strengthen the deep integration of medicine and science from the aspects of curriculum system setting, teacher team construction, practice teaching, and teaching method reform, and puts forward the innovative education model of the integration of medicine and science in applied psychology-medicine interdisciplinary training.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective:To observe the effect of bacteroides fragilis BF839 intervention on learning, memory and social novelty of fragile X-mental retardation gene 1 ( Fmr1) knockout (KO) mice. Methods:Thirty three-week-old Fmr1 KO mice were randomly divided into Fmr1 KO group ( n=15) and Fmr1 KO+BF839 group ( n=15). Mice in the Fmr1 KO group freely drank autoclaved tap water everyday; mice in the Fmr1 KO+BF839 group drank BF839 bacterial liquid (10 mL/d) everyday;11 wild-type mice freely drank autoclaved tap water everyday were set as controls (WT group). After 4 weeks of intervention, Morris water maze test was used to observe the differences in escape latency and frequencies of crossing the original platform among mice in each group; Three-chamber Social Interaction Test was used to observe the differences in contact frequencies and contact durations with unfamiliar mice among mice in each group. Results:On the 4 th d of experiment, the escape latency of mice in the Fmr1 KO group ([46.06±10.29] s) was significantly longer than that in the WT group ([33.39±12.02] s, P<0.05); the escape latency of mice in the Fmr1 KO+BF839 group ([28.39±9.07] s) was significantly shorter than that in the Fmr1 KO group ( P<0.05); the escape latency of mice in the Fmr1 KO+BF839 group was slightly shorter than that in the WT group without significant difference ( P>0.05). The frequencies of crossing through the original platform of mice in Fmr1 KO group (0.00[0.00, 1.00] time) was slightly less than that in WT group (1.00 [0.00, 1.00] time) without significant difference ( P>0.05); that in the Fmr1 KO+BF839 group (1.50[1.00, 2.00] times) was significantly larger than that in the Fmr1 KO group and WT group ( P<0.05). The contact frequencies of the mice in the Fmr1 KO group with unfamiliar mice (5.50[0.50, 12.75] times) was less than that in the WT group (7.00[4.00, 17.00] times) without significant difference ( P>0.05); that in the Fmr1 KO+BF839 group (23.00[16.00, 36.00] times) was significantly increased as compared with that in the Fmr1 KO group and WT group ( P<0.05). The contact duration of mice in the Fmr1 KO group with unfamiliar mice (9.50[0.50, 41.95] s) was significantly shorter than that in the WT group (142.00[65.00, 171.60] s, P<0.05); Fmr1 KO+BF839 group had significantly longer contact duration with unfamiliar mice (69.60 [50.40, 98.40] s) than Fmr1 KO group ( P<0.05); the contact duration of mice in Fmr1 KO+BF839 group with unfamiliar mice was shorter than that in WT group without significant difference ( P>0.05). Conclusion:Early BF839 intervention can significantly improve the learning, memory abilities and social novelty of Fmr1 KO mice, and even restore the Fmr1 KO mice to normal levels, which suggests that BF839 may become a new tool for treatment of fragile X syndrome and autism.

Objective:To analyze the risk factors of Intensive Care Unit-Acquired Weakness, and to develop and verify the model.Methods:A total of 247 patients admitted to ICU patients from November 2018 to October 2019 were selected, and risk factors between ICU acquired weakness group ( n=106) and non-ICU acquired weakness group( n=141)were compared using logistic regression for model construction.The Hosmer-Lemeshow test was used to verify the goodness of fit of the model. The area under the ROC curve was used to test the model to predict the effects. From November 2019 to May 2020, 106 patients were recruited for application of the model. Results:The incidence of ICU acquired weakness in this study was 42.91%(106/247), and 44.34%(47/106),the study finally included age ( OR=1.043) ,mechanical ventilation time ( OR=1.140) , APACHE II score ( OR=1.081) , blood sugar ( OR=1.117) , lactic acid( OR=1.459) ,and neuromuscular blockers ( OR=3.499) to construct the risk prediction. The model formula was P=1/1+exp (- Z) =1/1+exp (8.808-0.042×age -1.252×neuromuscular blockers-0.078×APACHE II score -0.110×blood sugar -0.378×lactic acid -0.131×mechanical ventilation time. The area under the ROC curve of this model was 0.896 (95% CI: 0.824-0.914) , the maximum value of the Youden index was 0.577, and the corresponding sensitivity was 0.754,the specificity was 0.823,the cutoff value was 0.503. The model verification results the sensibility of 70.2%, the specificity of 88.1%, and the accuracy of 80.2%. Conclusion:The predictic model of ICU acquired weakness couducted in this study has satisfactory prediction effect, which can provide a reference for clinical screening of high-risk patients.

Objective:To investigate the clinical practice of chronic kidney disease-mineral and bone disorder (CKD-MBD) in maintenance hemodialysis patients in Shanghai, and to better understand the changes of clinical practice for CKD-MBD.Methods:Sixty-four hospitals with qualified dialysis center in Shanghai were selected for questionnaire survey as of March 2019. The survey questionnaire included the number of hemodialysis and peritoneal dialysis patients, the implementation of CKD-MBD guidelines, the learning of CKD-MBD guidelines, the detection and distribution of CKD-MBD biochemical indicators, the treatment of hyperphosphatemia, the treatment of secondary heperparathyroidism (SHPT) and renal bone disease, and the concentration of calcium ion in dialysate. The results were compared with previous survey data in 2011.Results:There were sixty-three hospitals included in this study, with 10 168 maintenance hemodialysis patients and 4 610 maintenance peritoneal dialysis patients in Shanghai. 84.1%(53/63) hospitals implemented the guidelines smoothly, which increased by 28.5% compared with the rate (55.6%) of 2011. The successful implementation rates for guidelines in secondary and tertiary hospitals were 83.3%(25/30) and 84.8%(28/33) , which increased by 44.0% and 11.7% respectively (39.3% of secondary hospitals and 73.1% of tertiary hospitals in 2011). All hospitals carried out the detection for serum calcium and phosphorus. The rate for parathyroid hormone (PTH), total alkaline phosphatase (AKP), bone specific alkaline phosphatase (BAP), 25-hydroxy vitamin D[25(OH)D], and other bone metabolism-related biomarkers were 98.4%(62/63), 90.5%(57/63), 19.0%(12/63), 90.5%(57/63) and 42.9%(27/63), respectively; coronary artery CT, lumbar lateral X-ray plain, echocardiography, bone mineral density, and vascular ultrasound were carried out in 68.3%(43/63), 74.6%(47/63), 100.0%(63/63), 68.3%(43/63)and 69.8%(44/63), respectively. Compared with 2011, the proportion of detection for PTH, AKP, BAP, 25(OH)D, coronary artery CT, lumbar lateral film and echocardiography increased by 2.1%, 1.6%, 0.5%, 47.9%, 14.6%, 20.9% and 1.9%, respectively. The proportion of patients with serum phosphorus ranging in 0.80-1.45 mmol/L(KDIGO guideline), serum phosphorus ranging in 0.80-1.78 mmol/L(KDOQI guideline), calcium ranging in 2.10-2.54 mmol/L, and PTH ranging in 150-600 ng/L were 37.0%(3 323/8 969), 50.7%(4 571/9 018), 60.2%(5 568/9 244) and 33.2%(3 018/9 087). Compared with 2011(39.6%, 53.5% and 34.1%), the proportion of patients with ideal serum phosphorus (0.80-1.78 mmol/L) and calcium (2.10-2.54 mmol/L) levels increased by 11.1% and 6.7% respectively, and the proportion with PTH 150-300 ng/L decreased by 0.9%. The proportion of hospitals for using non-calcium phosphate binders (lanthanum carbonate from 1.9% to 87.3% and sevelamer carbonate from 14.8% to 63.5%) and surgical treatment (from 38.9% to 68.3%) for SHPT dramatically increased.Conclusions:Through the availability of medicine increases, and nephrologists gain deeper understanding in management and treatment of CKD-MBD, the detection rate for CKD-MBD indicators and the eligible rate have significantly improved compared with those in 2011. However, the comprehensive management of CKD-MBD in Shanghai still faces great challenges. It is still necessary to further improve eligible rate for serum phosphorus and iPTH, so as to provide more evidences and management strategies for integrated management of end-stage renal disease and prevention of abnormal calcium and phosphorus metabolism in patients.

Objective:To explore the risk factors for myelosuppression in elderly lung cancer patients undergoing chemotherapy and construct a risk prediction model for myelosuppression in elderly lung cancer patients undergoing chemotherapy.Methods:Using the convenient sampling method, data of 228 elderly patients with lung cancer undergoing chemotherapy in Respiratory Department of a Class Ⅲ Grade A hospital in Zhenjiang from May 2018 to May 2019 were selected, and risk factors of adverse reactions of myelosuppression in patients were analyzed statistically. The binomial Logistic regression was applied to construct the prediction model and the area under the ROC curve was used to test the prediction effect of the model. The patient data from January to May 2020 were collected to validate the model.Results:Among the 228 patients, 75 patients developed myelosuppression, with an incidence of 32.89%. Multivariate analysis results showed that platinum-containing chemotherapy regimens, combined with other adverse reactions, decreased albumin before chemotherapy and decreased hemoglobin before chemotherapy were independent risk factors for myelosuppression in elderly lung cancer patients during chemotherapy ( P<0.05) , which were included in the model. The area under the ROC curve of the final model was 0.823, the maximum Youden index was 0.5, sensitivity was 81.3%, and specificity was 70.5%. The results of the verification data showed that the area under the ROC curve was 0.846, sensitivity was 90.4% and specificity was 68.2%. Conclusions:The prediction effect of this model is good, which can provide reference basis for clinical treatment and formulating nursing measures to prevent myelosuppression.

Objective: To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage. Methods: Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate. Results: 32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34- ~ 21.15) mmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31- ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) mmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) mmol/L, respectively. Conclusion The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.