OBJECTIVE To explore the effect of Jinkui shenqi pill and its potential mechanism on diabetic nephropathy-related osteoporosis （DNOP） in rats. METHODS The rats were randomly divided into blank control group， control group， model group， Jingui shenqi pill low-， medium- and high-dose groups （0.62， 1.24， 2.48 g/kg）， and positive control group （denosumab 3 mg/ kg）， with 12 cases in each group. Except for the blank control group and the control group， models of DNOP were constructed in the remaining groups by high-glucose and high-fat forage， 3% fructose solution for feeding+intraperitoneal injection of streptozotocin solution. At 2 d after successful molding， Jingui shenqi pill low-， medium- and high-dose groups， and positive control group were given intragastric administration or subcutaneous injection of the corresponding drugs， once a day， for consecutive 8 weeks. After the last administration， bone mineral density （BMD） and serum bone metabolism-related indexes [osteocalcin （OC）， calcium， phosphorus， alkaline phosphatase （ALP）， tartrate-resistant acid phosphatase （TRAP）] were detected. The pathological changes of right femoral tissues were observed， and the expressions of receptor activator of NF-κB ligand （RANKL）/receptor activator of NF-κB （RANK）/osteoprotegerin （OPG） pathway-related mRNAs and proteins in left femoral tissues were detected. RESULTS Compared with the blank control group and the control group， there was rupture of bone trabecula and severe structural damage in the model group， and tissue space was obvious. BMD and ALP activities， mRNA and protein expressions of OPG were significantly decreased or down-regulated， while the levels of OC， calcium and phosphorus， TRAP activity， mRNA and protein expressions of RANKL and RANK were significantly increased or up-regulated （P＜0.05）. Compared with the model group， the number of bone trabeculae was increased in all Jingui shenqi pill groups， and the arrangement of bone trabeculae was more regular and dense. The above indexes generally were improved in a certain dose-dependent manner （P＜0.05）. CONCLUSIONS Jingui shenqi pill can promote osteogenesis and regulate the balance of bone metabolism in DNOP rats， which may be related to down-regulating the expressions of RANKL and RANK， and up-regulating the expression of OPG.

The ethical dilemma in scientific research exists at all stages of the scientific research activities among medical graduate students,mainly involving conflicts of interest,clinical trials,animal experiments,and the relationship between teachers and students.If medical graduate students are in the ethical dilemma in scientific research for a long time,their research activities will be greatly affected.By discussing the connotation,evaluation tools,current situation,influencing factors,and improvement measures of ethical dilemmas in scientific research,this paper proposed some suggestions,such as comprehensively investigating the influencing factors of ethical dilemmas in scientific research,and formulating targeted improvement measures,with a view to helping medical graduate students identify and get rid of ethical dilemmas in scientific research,and promote the stability of research activities.

Objectives:To investigate the predictive effect of regional homogeneity (ReHo) from resting-state functional magnetic resonance imaging (rs-fMRI) in acute phase on memory function of chronic phage in ischemic stroke patients and the effects of residual learning (REL) on the predictive performance of machine learning models.Methods:From June 2019 to June 2021, rs-fMRI data of one-week after stroke (acute phase) were collected from 35 first-time ischemic stroke patients, and their memory scores were assessed by the Rey auditory verbal learning test (RAVLT) at 6 months after stroke (chronic phase). Using ReHo from rs-fMRI data in acute phase of ischemic stroke patients, the support vector regression (SVR) and the REL-based SVR (REL-SVR) were constructed to predict the patients’ memory scores at 6 months after stroke, and the performance of the two models was compared using Pearson correlation coefficient.Results:Based on the ReHo from acute phase, the correlation coefficient between the predicted values and the true scores from the SVR model was r=0.524, P=0.001, while the correlation coefficient obtained by the REL-SVR model was r=0.671, P<0.001. Brain regions with relatively higher weights such as Temporal_Pole_Mid_R (weight value: 1.03), Temporal_Mid_R(weight value: 1.03), Temporal_Inf_R (weight value: 1.03), Occipital_Mid_R (weight value: 0.57), Frontal_Mid_L (weight value: 0.32), Frontal_Sup_Medial_L (weight value: 0.53), SupraMarginal_L (weight value: 1.54), Calcarine_L (weight value: 0.65), Lingual_L (weight value: 0.58), Cuneus_L (weight value: 0.65), Precuneus_L (weight value: 0.83), cerebellum(weight value>1.0) made larger contributions to the prediction model. Conclusions:ReHo in the acute-phase can effectively predict memory in the chronic phase of ischemic stroke patients. Furthermore, REL can improve the performance of the traditional SVR model and achieve higher predictive accuracy.

ObjectiveTo investigate the protective effect of Zuoguiwan against ⁶⁰Co-γ ray-induced premature aging of rats based on the phosphatidylinositol-3-kinases/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway. MethodSixty sexually mature female SD rats were irradiated with ⁶⁰Co-γ rays （6.0 Gy， LD₄₀） for 24 h at one time. Then they were randomized into model group， Bujiale group （0.18 g·kg^-1·d^-1）， Bujiale （0.09 g·kg^-1·d^-1） + high-dose Zuoguiwan group （23.625 g·kg^-1·d^-1）， high-dose Zuoguiwan group （23.625 g·kg^-1·d^-1）， medium-dose Zuoguiwan group （9.45 g·kg^-1·d^-1）， and low-dose Zuoguiwan group （4.725 g·kg^-1·d^-1）. The administration （once a day） lasted 21 days. Serum indexes ［follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E₂）］ of rats were detected by enzyme-linked immunosorbent assay （ELISA）， and morphological changes of ovarian tissues were observed based on hematoxylin and eosin （HE） staining. The apoptosis rate of granulosa cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） and the protein expression of phosphorylated （p）-PI3K， p-Akt， p-mTOR， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in ovarian tissues by Western blot. ResultCompared with normal group， model group demonstrated increase in serum FSH （P<0.01）， decrease in E₂ （P<0.05）， and reduction of follicles and luteum in early ovary （P<0.01）. Moreover， the elevation of apoptosis rate of granulosa cells （P<0.01）， down-regulation of p-PI3K， p-Akt， p-mTOR， and Bcl-2 in ovarian tissue， and increase in expression of Bax were also observed in the model group as compared with the normal group （P<0.01）. In comparison with the model group， the administration groups showed rise of the number of early ovarian follicles， decrease in the apoptosis rate of granulosa cells， increase in the expression of p-PI3K， p-Akt， p-mTOR， and Bcl-2， and down-regulation of Bax， particularly the Bujiale + high-dose Zuoguiwan group（P<0.05，P<0.01）. ConclusionZuoguiwan protects radiation-damaged ovary by activating the expression of PI3K/Akt/mTOR protein in ovarian tissue， increasing Bcl-2， and inhibiting the expression of Bax.

Bladder cancer(BC) ranks the first of genitourinary tumor in China and is one of the most common urological malignancies, in which 25%-30% of patients were diagnosed with muscle-invasive bladder cancer. Radical cystectomy combined with pelvic lymph node dissection is the standard procedure for treatment, which can effectively avoid tumor recurrence or distant metastasis as well as improve the prognosis of patients. However, some patients may not tolerate or refuse to undergo radical bladder surgery due to worry about high complication rate, high morbidity and poor postoperative quality of life. With the increasing understanding of bladder cancer heterogeneity and biological behavior, the treatment of bladder cancer has changed from a surgery-based treatment model to an individualized and comprehensive treatment model by multidisciplinary collaboration. The bladder-preserving treatment can achieve the same oncological prognosis as that of radical bladder surgery with a better quality of life of the patients, which has become a hot topic and focus of research in muscle-invasive bladder cancer treatment. This article reviewed the progress of research related to the comprehensive treatment of muscle-invasive bladder cancer with preservation of the bladder.

Objective:To develop an evidence-based nursing program for a patient with oral complications of dysphagia due to cerebral infarction.Methods:According to the principle of PICO, and the problem of patients' clinical manifestations, using the method of combining subject words and free words, the database of Uptodate, NICE, SIGN. RNAO, medical pulse guide network, BMJ, Cochranc library, PubMed, EMbase, CINAHL, China National Knowledge Infrastructure were searched and collected the clinical guidelines, systematic evaluation and randomized controlled trial of oral complications in patients with dysphagia of cerebral infarction.Results:Totally 1 clinical decision, 5 clinical guidelines, 4 expert consensus, 2 systematic evaluations, 1 Meta-analysis, 3 randomized controlled trial (RCT) were included. Based on the search results and the patient′s condition and wishes, nurses performed swallowing function tests every two days according to the Standard Swallowing function rating Scale (SSA), raised the head of the bed 40°~45° and holded it for 1 hour. Three times a day, the teeth were brushed with chlorhexidine oral care solution under negative pressure. Sputum scab was removed by mechanical scrubbing. The back of tongue was scrubbed by 6x tongue scraping technique every night. After the infection was controlled, the teeth were washed twice a day with 0.9% sodium chloride solution. Oral condition and swallowing function were evaluated daily. High flow humidification oxygen therapy and mask spray atomization inhalation were used. Swallowing training was performed on the third day after admission. Seven days after the evidence was applied to clinical practice, the oral mucosa was moist without peculiar smell and sputum scab, and the swallowing function was changed from grade IV to grade II.Conclusion:Nursing cerebral infarction patients with dysphagia, nurses should timely assess the patient's oral cavity and swallowing function, the application of chlorhexidine and 0.9% sodium chloride solution oral care solution mechanical scrubbing method and negative pressure washing brushing method can effectively remove sputum scab, use 6x tongue scraping technology to scrub the back of tongue, can reduce micro organisms, reduce halitosis; the application of nasal mask high flow humidification oxygen therapy and spray atomization inhalation humidification effect is obvious Therefore, early swallowing training can reduce the incidence of oral complications.

【Objective】 To establish and evaluate a nephelometric assay for the determination of immunoglobulin A (IgA) residues in human intravenous immunoglobulin(IVIG). 【Methods】 BN ProSpec^© automatic protein analyzer and its supporting immunoglobulin A determination kit (nephelometry) produced by German Siemens and the national standard of human IgA were used to establish the nephelometric assay to determine IgA residue in test products and verify the methodology. The test products include IVIG (pH4) prepared by low-temperature ethanol protein separation process and a novel IVIG prepared by chromatography. 【Results】 The average deviation of three calibration curves for IgA residues determination by the nephelometric assay were 1.08%, 0.95% and 1.54%,, and the three deviations of the quality control were 4.00%, -2.30% and -0.20%, respectively, which indicated good calibration and quality control. In the specificity test, the average recovery rates of IgA for reference substance 1 containing 100g/L maltose and reference substance 2 containing 20g/L glycine were 102.7% and 105.8%, respectively. The relative standard deviation (RSD) values of the repeatability tests of the two test products were 3.9% and 1.9%, and the RSD values of the intermediate precision test were 3.6% and 2.3%, respectively.The difference values at each time point in the durability test of test products′ storage time were all less than 10%, and the RSD values of the two test products in the durability test of kits of different batches were 2.8% and 2.2%, respectively. In the accuracy test, the average recovery rates of IVIG (pH4) added to the standard were 94.2%, 101.7% and 96.2%, respectively, and the average recovery rates of the novel IVIG added to the standard were 102.8%, 106.3% and 99.7%, respectively. The average recovery rate of the limit quantification test was 101.0%, and the RSD was 4.0%. 【Conclusion】 Nephelometric assay has the advantages of strong specificity, high precision and accuracy, good repeatability, simple and rapid operation, and automation, and can be used for the determination of IgA residue in IVIG (pH4) and novel IVIG products.

Objective:To explore the correlation between single nucleotide polymorphisms (SNPs) in Homo sapiens longevity assur-ance homologue 2 (LASS2) gene 3′-untranslated regions (UTR) and susceptibility of bladder cancer among residents of Yunnan, China. Methods:A total of 105 bladder cancer patients (bladder cancer group) and 100 nonbladder cancer patients (control group) were se-lected. PCR method and sequence for LASS2-3′-UTR were performed to identify the SNPs correlated with bladder cancer. The relation-ships between the LASS2-3′-UTR polymorphisms and bladder cancer risk were analyzed. Results:An SNP (rs8444) was identified in LASS2-3′-UTR, and the T/C allele frequencies and genotype distributions of rs8444 largely differed between the bladder cancer and control groups (χ2=10.267, P=0.006;χ2=10.634, P=0.001). Individuals that carry the rs8444 C allele or CC genotype had a remarkably lower risk of bladder cancer compared with those that carry the T allele or TT genotype (OR=0.489, 95%CI:0.309-0.772, P=0.002;OR=0.258, 95%CI:0.081-0.827, P=0.023). No significant correlations were observed between the T/C allele frequencies and genotype distri-butions of rs8444 and TNM stage, as well as histological grade and distant metastasis in bladder cancer (P>0.05). Conclusion: The rs8444 C allele or CC genotype located within LASS2-3′-UTR can lower the susceptibility of bladder cancer among the residents of Yun-nan, China. However, it is not associated with the TNM stage, histological grade, and distant metastasis.

Fatigue is commonly experienced in patients with advanced kidney disease and associated with poor outcomes. The purpose of this review was to discuss the prevalence, assessment methods and contributing factors of fatigue in patients with end-stage renal disease (ESRD), and also examined possible interventions to improve fatigue and concludes by defining some future research directions.

OBJECTIVE:To establish the method for simultaneous determination of 6 components in Lonicera japonica,and to study the content changes of them before and after before and after carbonized. METHODS:UPLC method was adopted. The deter-mination was performed on Agilent Eclipse Plus C18 RRHD column with mobile phase consisting of 0.1% phosphoric acid solu-tion-acetonitrile(gradient elution)at the flow rate of 0.2 mL /min. The detection wavelength was set at 350 nm,and column tem-perature was 25 ℃. The sample size was 1 μL. RESULTS:The linear ranges of chlorogenic acid,rutin,galuteolin,isochlorogenic acid A,isochlorogenic acid B and isochlorogenic acid C were 21.2-424 μg(r=0.9993),1.17-23 μg(r=0.9995),2.18-43 μg(r=0.9998),5.10-102 μg(r=0.9993),2.60-52 μg(r=0.9991),4.95-99 μg(r=0.9998),respectively. RSDs of precision,stability and repeatability tests were all lower than 2.0%. Recoveries were 97.11%-99.76%(RSD=1.20%,n=6),95.20%-99.90%(RSD=2.20%,n=6),95.71%-100.30%(RSD=2.20%,n=6),95.00%-96.98%(RSD=0.88%,n=6),96.47%-103.00%(RSD=2.40%, n=6),95.78%-103.80%(RSD=3.20%,n=6). Compared with before processing,the contents of rutin,isochlorogenic acid B and isochlorogenic acid C in L. japonica were increased along with processing,the contents of chlorogenic acid and isochlorogenic acid A were decreased significantly,while the content of galuteolin had no significant change. CONCLUSIONS:The method is sim-ple,precise,stable and repeatable,and can be used for simultaneous determination of 6 components in L. japonica. Those chemi-cal components have certain changes before and after carbonized.