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Lymphoplasmapheresis(LPE) is a combination of plasma exchange and lymphocyte separation technology. It can not only remove autoimmune antibodies, but also remove the immune active cells producing these antibodies. At the same time, it can inhibit cellular and humoral immune responses, and improve the efficiency and reliability of treatment. This technology is safe, reliable, and easy to operate. In recent years, it has been widely used in the treatment of various autoimmune diseases and the suppression of immune rejection after organ transplantation, especially in the treatment of critically ill patients. This paper summarizes the clinical application status of LPE in immune-related diseases at home and abroad, analyzes the problems existing in the clinical promotion of LPE, and makes a prospect of its application value.
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Endogenous ribonucleotides(RNs)and deoxyribonucleotides(dRNs)are important metabolites related to the pathogenesis of many diseases.In light of their physiological and pathological significances,a novel and sensitive pre-column derivatization method with N-(t-butyldimethylsilyl)-N-methyltri-fluoroacetamide(MTBSTFA)was developed to determine RNs and dRNs in human cells using high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).A one-step extraction of cells with 85％methanol followed by a simple derivatization reaction within 5 min at room temper-ature contributed to shortened analysis time.The derivatives of 22 nucleoside mono-,di-and tri-phosphates were retained on the typical Cig column and eluted by ammonium acetate and acetonitrile in 9 min.Under these optimal conditions,good linearity was achieved in the tested calibration ranges.The lower limit of quantitation(LLOQ)was determined to be 0.1-0.4 μM for the tested RNs and 0.001-0.1 μM for dRNs.In addition,the precision(CV)was＜15％and the RSD of stability was lower than 10.4％.Furthermore,this method was applied to quantify the endogenous nucleotides in human colorectal carcinoma cell lines HCT116 exposed to 10-hydroxycamptothecin.In conclusion,our method has proven to be simple,rapid,sensitive,and reliable.It may be used for specific expanded studies on intracellular pharmacology in vitro.
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Drug optimization, which improves drug potency/specificity by structure‒activity relationship (SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However, the current drug optimization may overlook the structure‒tissue exposure/selectivity-relationship (STR) in disease-targeted tissues vs. normal tissues, which may mislead the drug candidate selection and impact the balance of clinical efficacy/toxicity. In this study, we investigated the STR in correlation with observed clinical efficacy/toxicity using seven selective estrogen receptor modulators (SERMs) that have similar structures, same molecular target, and similar/different pharmacokinetics. The results showed that drug's plasma exposure was not correlated with drug's exposures in the target tissues (tumor, fat pad, bone, uterus), while tissue exposure/selectivity of SERMs was correlated with clinical efficacy/safety. Slight structure modifications of four SERMs did not change drug's plasma exposure but altered drug's tissue exposure/selectivity. Seven SERMs with high protein binding showed higher accumulation in tumors compared to surrounding normal tissues, which is likely due to tumor EPR effect of protein-bound drugs. These suggest that STR alters drug's tissue exposure/selectivity in disease-targeted tissues vs. normal tissues impacting clinical efficacy/toxicity. Drug optimization needs to balance the SAR and STR in selecting drug candidate for clinical trial to improve success of clinical drug development.
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Objective:To assess the value of the parotid fat fraction (FF) and T 2 relaxation time (T 2 value) in the evaluation of early parotid involvment in patients with primary Sj?gren′s syndrome (pSS) using multi-echo Dixon technique and T 2 mapping imaging. Methods:From December 2018 to December 2019, 26 early pSS patients (pSS group) and 20 healthy controls (control group), matched to age and gender, were enrolled at the First Affiliated Hospital of Zhengzhou University in this prospectively study. All subjects underwent conventional MRI, DWI, multi-echo Dixon and T 2 mapping sequences before treatment. The ADC, FF and T 2 value of bilateral parotid parenchyma in pSS group and control group were measured respectively. Paired sample t test was used to compare the differences of ADC, FF and T 2 values between left and right parotid glands for pSS group and control group, while independent sample t test was used to compare the differences of ADC, FF and T 2 values between pSS group and control group. The ROC curves were drawn to evaluate diagnostic performance of ADC, FF and T 2 values to distinguish early pSS, and the difference of diagnostic efficacy of each parameter was compared by Delong test. Binary logistic regression analysis and ROC curve were used to evaluate the diagnostic performance of the combination of the 3 parameters in early pSS. Results:There were no significant differences of ADC, FF and T 2 values between left and right parotid glands for pSS group and control group (all P>0.05). The parotid ADC values were significantly lower in pSS group than control group ( t=4.641, P=0.006), while the FF and T 2 values of pSS group were significantly higher than those of control group ( t=-2.910, -6.411, both P<0.001). The areas under the ROC curve of ADC, FF and T 2 values to distinguish early pSS were 0.666, 0.750 and 0.862, respectively. The area under ROC curve of the combination of ADC, FF and T 2 values was 0.930, with a sensitivity of 73.1% and a specificity of 97.5%. T 2 values showed a better diagnostic efficacy than ADC values ( Z=2.626, P=0.009) and FF values ( Z=2.112, P=0.035) when distinguishing pSS group from control group. The area under ROC curve of the combination of ADC, FF and T 2 values showed a better diagnostic efficacy than each parameter alone ( Z=4.869, P<0.001, Z=3.628, P<0.001, Z=2.162, P=0.031). Conclusions:Multi-echo Dixon technique and T 2 mapping can quantitatively evaluate the parotid gland fat deposition and inflammatory response in the early stage of pSS. T 2 value has great potential in evaluating early parotid gland injury of pSS, and the combination of ADC, FF and T 2 values can further improve the diagnostic efficiency.
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Objective:To analyze the predictors of systemic lupus erythematosus (SLE) with intestinal symptoms as the first manifestation, and to provide evidence for the diagnosis and differential diagnosis of the disease.Methods:From January 2013 to June 2020, the clinical data of 165 patients diagnosed with SLE and treated at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. According to whether the intestinal symptoms were the first manifestations, they were divided into intestinal symptoms as the first manifestations group ( n=50) and intestinal symptoms not as the first manifestations group ( n=115). The baseline data, imaging findings, orgen involvement and laboratory indicators of the two groups were compared and analyzed. Independent sample t test, non-parametric test and chi-square test were used for statistical analysis. Logistic regression analysis was used to establish a prediction model of SLE with intestinal symptoms as the first manifestation. Receiver operating characteristic curve (ROC) and Hosmer-Lemeshow test were used to evaluate the predictive value of the model. From July 2020 to May 2021, the data of 72 SLE patients treated at the First Affiliated Hospital of Zhengzhou University were collected (22 patients with intestinal symptoms as the first manifestation and 50 patients with intestinal symptoms not the first manifestation), and the predictive power of the model was validated. Results:Compared with intestinal symptoms not as the first manifestation group, the proportions of patients with fever, muscle involvement and joint involvement in intestinal symptoms as the first manifestation group were lower, while the proportions of patients with polyserositis, ascites, edema and dilatation or thickening of intestines, hydronephrosis or dilatation of the ureter, kidney involvement, blood system involvement were higher, and the level of complement C3, level of complement C4, absolute lymphocyte value and albumin level were lower (67.8%, 78/115 vs. 32.0%, 16/50; 24.3%, 28/115 vs. 4.0%, 2/50; 68.7%, 79/115 vs. 14.0%, 7/50; 27.8%, 32/115 vs. 86.0%, 43/50; 16.5%, 19/115 vs. 78.0%, 39/50; 13.9%, 16/115 vs. 86.0%, 43/50; 4.3%, 5/115 vs. 62.0%, 31/50; 29.6%, 34/115 vs. 48.0%, 24/50; 30.4%, 35/115 vs. 52.0%, 26/50; 0.76 g/L, 0.43 to 0.97 g/L vs. 0.48 g/L, 0.40 to 0.57 g/L; 0.14 g/L, 0.08 to 0.23 g/L vs. 0.09 g/L, 0.06 to 0.15 g/L; 0.90×10 9/L, 0.51×10 9 to 1.28×10 9/L vs. 0.64×10 9/L, 0.44×10 9 to 1.08×10 9/L; (34.07±7.30) g/L vs. (28.77±5.43) g/L), and the differences were statistically significant ( χ2=18.246, 9.699, 41.776, 47.567, 57.781, 78.833, 67.903, 5.195 and 6.955, Z=-4.053, -3.295 and -2.204, t=-4.606; all P<0.05). The results of multivariate logistic regression analysis showed that low level of complement C3 and low albumin level were risk factors of SLE with intestinal symptoms as the first manifestation (odds ratio 0.136, 95% confidence interval 0.031 to 0.590; odds ratio 0.923, 95% confidence interval 0.871 to 0.977; P=0.008 and 0.006). The established prediction model for SLE with intestinal symptoms as the first manifestation was p=1/(1+ e - Y), in which Y=2.906-1.994×complement C3 (g/L) -0.08×albumin (g/L). The area under the ROC was 0.761 (95% confidence interval 0.687 to 0.834, P<0.01). The result of Hosmer-Lemeshow test showed the model had good calibration ability ( χ2=13.024, P=0.111). The result of validation analysis showed that when p≥0.255 to predict SLE with intestinal symptoms as the first symptoms, the sensitivity of the model was 72.7% (16/22), the specificity was 76.0% (38/50), and the accuracy was 75.0% (54/72). Conclusions:The symptoms of SLE with intestinal symptoms as the first manifestations are obscure and easily misdiagnosed. When the imaging examination of patients with intestinal symptoms as the first manifestations shows edema and dilatation or thickening of intestines, hydronephrosis or dilatation of the ureter, or laboratory examination indicates low level of complement C3 and low albumin level, be wary of the possibility of SLE. Early diagnosis and intervention can greatly improve the prognosis of patients.
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Objective To explore the impact of WeChat-assisted follow-up on self-administer medication capability of stroke survivors.Methods Seventy patients were recruited from a tertiary hospital and randomly divided into intervention group (n=35) and control group (n=35).Patients in intervention group were given WeChat-assisted follow-up including health education program and behavior guidance,and patients in control group received regular discharge care.The effects of WeChat-assisted follow-up and regular care on self-administer medication ability,cognitive and behavior level were assessed.Results After three months' follow-up,the scores of self-administer medication capability (38 (32,42)),experience (25 (20,28) and the integral level (87 (71,92)) in intervention group were significantly higher than those in control group (capability 25(16,38),experience 21 (8.75,27),total score 68 (38,87)) (Z=-2.511,-2.033,-2.209,P＜0.05).The self-administer medication experience,cognitive,capability and total scores increased significantly in intervention group after intervention(Z=-4.525,-4.610,-3.806,-4.718,all P＜ 0.01),while only the cognitive level increased slightly in control group (18 (10,24) vs 13 (11,18),Z =-1.794,P=0.073).Conclusions Follow-up intervention based on WeChat platform can improve the stroke patients' self-administration medication capability,however,the long-term effects on cognitive level and further reform need to be strengthened.
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@#The stroke patients at home have many problems, such as knowledge, medication, monitoring and rehabilitation, which results in poor rehabilitation effect, and the patients need home care urgently. Smartphone applications can provide disease knowledge, health monitoring, drugs reminder, rehabilitation guide and system management, as well as social activities and emergency treatment strategy supplying, which can provide a new home care method for stroke patients. However, there are also many deficiencies, such as simple function design, lack of medical institutions participation in the design, lack of authoritative quality evaluation tool, limitations in users and potential safety hazard.
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@#Mbile Health has been recommended by World Health Organization, and mostly actualized by smartphone application (APP). Home patients with stroke accept APP well, and the acceptance of APP relates with the factors of patients, APP and society. Acceptance of APP may be improved by the improvement of technical support, user experience and usability.
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Objective To investigate the toxic reaction,toxic organs or target tissues of protamine recombinant human insulin (Insulin NPH),and provide basis for clinical trials by single dose toxicity test in mice,repeated toxicity and immunogenicity of Beagle's dogs,and systemic active allergy in guinea pig.Methods ① Using maximum dose method,mice in single dose toxicity test were sc injected with normal saline (NS),vehicle,and Insulin NPH (2092-2488 IU/kg),the toxic reactions after injection were monitored.② In repeated toxicity study,Beagle's dogs were sc administrated with vehicle,the original (Humulin NPH,1.5 IU/kg)and different doses of Insulin NPH (0.5,1.0 and 1.5 IU/kg) for 30 d continuously,followed by a 14-d recovery.During the administration and recovery period,general observation,local irritation,body weight,anus temperature,blood glucose,and electrocardiogram (ECG) were checked,moreover,hematology,serum biochemistry and urine were detected.Also,organic weights and histopathological examination were conducted.Binding antibodies in dog serum were measured by indirect ELISA method in immunogenicity test.③ In systemic active allergy study,cavies were sc injected with low-and high-dose (4 and 12 IU/kg) Insulin NPH,normal saline and vehicle.Besides,ova as positive control was also included.After five times of sensitization test with above doses,the excitation reactions of iv injection with tripled sensitizing doses were observed.Results No obvious toxicity was observed in mice after injected with 165 times of usual clinical dose of Insulin NPH.Repeated toxicity study of Beagle's dogs revealed that 1.0 IU/kg was the no-toxic-effect dose (NOAEL) for Insulin NPH,which was equivalent to 2 times of clinical dose.No bindingantibodies were found in immunogenicity test.There was no obvious allergic symptom in the active systemic allergy study of guinea pig.Conclusion Under the experimental conditions,no serious toxicity of Insulin NPH is found.
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Objective To investigate the effect of solution-focused therapy on the care burden and negative emotions of the primary caregivers with elderly patients with hip fractures. Methods One hundred and sixty-eight elderly patients with hip fractures and caregivers were divided into intervention group and control group with 84 pairs by random digits table method, and the two groups were given continual nursing care. At the same time, the primary caregivers of intervention group accepted the solution-focused therapy. Caregiver Burden Inventory (CBI), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were used as the evaluation indexes. Results Before intervention, the score of CBI, SAS,SDS was (42.07 ± 4.24), (50.75 ± 11.21), (51.59 ± 13.18) points in control group and (42.10 ± 3.96), (50.48 ± 12.59), (52.96 ± 13.51) points in intervention group, and there was no significant differences between two groups (P>0.05). After intervention, the score of CBI, SAS, SDS was (40.49±3.17), (50.64±11.33), (50.14±10.25) points in control group and (28.95±2.87), (36.73±9.45), (41.60±8.23) points in intervention group, and there was significant differences between two groups (t=5.42, 8.73, 7.45, all P<0.05). Conclusions Solution-focused therapy can effectively reduce the care burden of the primary caregivers of elderly patients with hip fractures and alleviate their anxiety and depression.
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Objective To localize the upper airway obstruction of patients with obstructive sleep apnea hypopnea syndrome (OSAHS)with the Cinema Magnetic Resonance(Cine-MR) and fiber optic laryngoscope with Müller maneuver(FLMM)before operation and discuss the clinical application values.Methods Before operation, FLMM and Cine-MR were applied to 22 patients diagnosed as OSAHS by Polysomnography(PSG).Medical examinations conducted in this study from September 2015 to April 2016 to examine the obstruction of the soft palate region, the lingual region and epiglottis.Results There were complete agreements between the Cine-MR and FLMM at locating obstruction sites of the soft palate (n=22/n=22),and there were moderate agreements between the Cine-MR and FLMM in locating obstruction sites of the retroglottal region(n=13/n=6),epiglottal region (n=4/n=2)and multiple level(n=13/n=6), respectively.Conclusion For those moderate and severe OSAHS patients with multiple sites obstruction , the preoperative application of the Cine-MR and FLMM together will be better in locating the obstruction sites.
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OBJECTIVE:To explore the characteristics and regularities of cardiac damage induced by metranidazole,and pro-vide reference for clinical safe application. METHODS:In retrospective study,58 cases of cardiac damage caused by metranidazole in Henan ADR Monitoring Center for Drug from Jan. 2010 to Dec. 2015 were analyzed statistically. RESULTS:In 58 cases of cardiac damage induced by metranidazole,25 cases were male,33 were female,the ratio of male to female was 0.76∶1,the patients with ADR/ADE aged 15-64 years (74.14%),most were intravenous administration (79.31%) and happened within 30 min (70.69%), cardiac damage mainly manifested as palpitation,severe cases can cause tachycardia and arrhythmia,the ADR improved or cured af-ter withdrawal or symptomatic treatment. CONCLUSIONS:Clinic should strengthen observation of ADR/ADE caused by metranida-zole,especially the monitoring of cardiac toxicity reactions;pharmaceutical manufacturers should improve the drug instructions to in-sure the safety of clinical medication.
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OBJECTIVE:To investigate the effects of different operation methods on the residual amount of docetaxel. METH-ODS:60 Docetaxel injections were selected and divided into two groups,i.e. standard operation method was adopted in group A (30 injections),and clinical common operation method was used in group B(30 injections). Docetaxel injections were placed for 5,10 or 15 minutes respectively,and drained. Residual liquid was collected to calculate residual amount. The difference of residual amount,due to preparation method and standing time,were compared between two groups. RESULTS:After placing for 5,10 or 15 min,the volume and amount of residual liquid in group B were significantly higher than in group A(P<0.05). In same group, the volume and amount of residual liquid after placing for 10 and 15 min were all lower than that after placing for 5 min(P<0.05 or P<0.01);the volume and amount of residual liquid after placing for 15 min were lower than that after placing for 10 min(P<0.05). CONCLUSIONS:The standard operation of pharmacy dispensing staff is very important to reduce the residual amount of docetaxel,and guarantee safe,effective and sufficient medication. It is suggested that clinical staff should abide by standard opera-tion method.
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Objective To explore the clinical efficacy of captopril combined with nifedipine in the treatment of type 2 diabetes mellitus complicated with hypertension.Methods 100 patients with type 2 diabetes mellitus complicated with hypertension were divided into two groups by randomized single blind method.The two groups were given conventional hypoglycemic therapy,50 cases in the control group were treated with captopril,while 50 cases in observation group received captopril combined with nifedipine sustained -release tablets.The clinical therapeutic effect was compared between the two groups.Results The effective rate of the observation group was 94%,which of the control group was 80%,the difference was statistically significant (χ2 =9.65,P<0.05).After treatment,the diastolic blood pressure[(80.45 ±3.65)mmHg],systolic blood pressure[(128.67 ±5.66)mmHg],fasting blood glucose[(6.65 ±0.37)μmol/L],2h postprandial blood glucose[(9.76 ±1.22)μmol/L]of the observation group were significantly reduced than before treatment (t =8.06,8.18,8.00,7.94,all P <0.05),and diastolic blood pressure and systolic blood pressure were significantly different with the control group(t=8.66,7.90,all P<0.05). After treatment,the serum creatinine (97.44 ±6.32)μmol/L,urea nitrogen (4.20 ±0.30) mmol/L and 24h urinary albumin (17.99 ±4.10) mg/L of the observation group were significantly reduced compared with before treatment (t=7.67,8.27,8.32,all P<0.05),and the indicators had significant differences with the control group(t=7.23, 7.65,7.67,all P<0.05).Conclusion Captopril and nifedipine sustained-release tablets in the treatment of type 2 diabetic patients with hypertension can effectively reduce the blood pressure,improve renal function,and it has good clinical application and promotion value.
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Objective To investigate the value of qualitative and quantitative parameters of MRI on diagnosis of benign and malig-nant breast lesions.Methods Patients were scanned with MRI who were confirmed as breast lesions verified by histopathology,and the time-signal curve(TIC),Slopemax ,the apparent diffusion coefficient values (ADC)were deduced.Results There were 24 benign and 11 malignant lesions.Features of benign lesions were shown as follow:The TIC type wasⅠmostly 91.7%,Slopemax was 0.65 %/s,the ADC values was 1.31×10 -3 mm2/s.Features of malignant lesions were shown as follow:The TIC type were Ⅱ and Ⅲ mostly (100%), Slopemax was 1.63 %/s,the ADC values was 1.06 ×10 -3 mm2/s.Conclusion Types of TIC,Slopemax ,the ADC values of MRI are valuable in the diagnosis of benign and malignant breast lesions,integrated functional parameters are better than an individual param-eters in that they can improve the accuracy of diagnosis.
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Objective to investigate the clinical application value of endometriosis fertility index (EFI) in the evaluation of ab‐dominal surgery endometriosis(EMT) combined infertility patient .Methods the date of 105 cases of infertility EMT merge were retrospectively analyzed from January 2009 to January 2013 in the Yuanzhou MCH and the obstetrics and gynecology department of Yuanzhou people′s hospital .All patients were followed up for two years and the rates of cumulative pregnancy were compared .Re‐sults the rates of two year cumulative pregnancy rate were 64 .80% (68 cases) .The two year cumulative pregnancy rates of EFI score ≤ 4 points ,5 to 7 points ,8 to 10 points were 34 .48% ,57 .14% ,92 .68% (P0 .05) .Conclusion EFI and EMT with infertility pregnancy after conser‐vative treatment has a close relationship ,and EFI score would provide important guidance for follow up treatment .
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Objective To evaluate the correlation of Omentin-1, the high sensitivity C-reactive protein (hsCRP) and coronary heart disease (CHD). Methods Sixty-eight patients with CHD were divided into the unstable angina pectoris (UAP) group (n=36), stable angina pectoris (SAP) group (n=32). And 30 normal subjects without CHD diagnosed by coronary arteriography (CAG) were served as the control group. The serum level of Omentin-1 was measured by enzyme linked immu-nosorbent assay (ELISA) and the serum level of hsCRP was measured by turbidmetric immunoassay. Results The serum level of Omentin-1 was significantly lower, but the serum level of hsCRP was significantly higher in CHD group than that of control group (P0.05). The serum level of Omentin-1 was significantly lower in patients with single, double and three-vessel lesion group than that of control group, but the serum level of hsCRP was significantly higher in CHD group than that of control group (P0.05). The se-rum level of Omentin-1 was negatively correlated with serum level of hsCRP (P<0.01). Conclusion The serum level of Omentin-1 and hsCRP may correlate with CHD, but which may not reflect the severity of artery stenosis.
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Objective To learn students' satisfaction with the general education courses, discuss the problems in comprehensive general education courses in local medical colleges , and provide the basis and reference for the medical general education courses reform. Methods Using the stratified random sampling method, self-designed questionnaire to local medical colleges of 575 different professions stu-dents. The questionnaire had the total of 54 topics whose contents were related to the basic situation aware-ness and satisfaction, the demand for general education courses, general education curriculum problems and suggestions. The survey data were analyzed using SPSS 19.0 software and the results were expressed by the relative number(rate and percentage). The differences between different majors and different grade student satisfaction were analyzed by using rank-sum test, showing statistical significance(P<0.05). Results The total satisfaction was not very high, only 219 students(38%) were satisfied with general curriculum;256 students(45%) thought it didn't matter whether to set general education courses;100 students(17%) were not satisfied. In addition, satisfaction with different grades was undifferentiated (P=0.798), but there was a statistical difference among the students of different professions(P=0.007). Conclusion The general education curriculum of medical schools should not blindly pursue being wide and full. Instead, it should be built from three aspects such as core curriculum, flexible teaching methods, teaching methods reform to enhance teaching effectiveness.
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@#Objective To observe the effect of community-based rehabilitation stroke unit on the function of stroke patients. Methods 94 patients with stroke were divided into intervention group (n=47) and control group (n=47). The control group accepted routine community home care, while the intervention group accepted community-based rehabilitation stroke unit care. They were assessed with modified Barthel index (MBI), simple Fugl-Meyer assessment (FMA) and Social Disability Screening Schedule (SDSS) before and after intervention. Results There was not significant difference between the groups in scores of MBI, FMA and SDSS (P>0.05) before intervention. All the scores improved significantly in both groups (P<0.01) 3 months after intervention, and improved more in the intervention group than in the control group (P<0.05). Conclusion Community-based rehabilitation stroke unit can improve the functional recovery of stroke patients.
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ObjectiveTo investigate the association of HLA-Cw alleles with inflammatory bowel disease(IBD), so as to identify IBD susceptibility gene.MethodsThe HLA-Cw genotype were analyzed in 100 patients with ulcerative colitis (UC), 73 patients with Crohn's disease (CD) and 106 randomly ethnically matched healthy controls by sequence specific primer polymerase chain (PCR-SSP).Results HLA-Cw * 07 gene phenotype frequencies increased in patients with UC (0.430) compared with that in healthy controls (0.226), P = 0.002; while HLA-Cw * 12 gene phenotype frequencies increased in patients with CD (0.356) compared with that in healthy controls (0.123), P = 0.000.ConclusionHLA-Cw * 07 allele and HLA-Cw * 12 allele may be strongly associated with the susceptibility of UC and CD, respectively.