Objective To investigate the mechanism of action of Guizhi Fuling pill in treating chro-nic prostatitis(CP)using network pharmacology and molecular docking techniques.Methods Compo-nents of Guizhi Fuling pill were collected from the Traditional Chinese Medicines Systems Pharmacolo-gy Platform(TCMSP),and target information was obtained from the SwissTarget database.Targets for chronic prostatitis were screened from the GeneCards,OMIM,CTD,and DisGeNET disease data-bases.A protein-protein interaction(PPI)network was established and analyzed.Gene ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway en-richment analysis were performed using the DAVID database.The Cytoscape software was employed to construct an association network linking the components of Guizhi Fuling Pill,their targets,and the targets of chronic prostatitis.Molecular docking was conducted using AutoDock Vina software to verify the binding stability between the components of Guizhi Fuling pill and their targets.Results After screening and deduplication in the TCMSP database,76 components of Guizhi Fuling Pill were iden-tified,and 655 component targets were retrieved from the SwissTarget database.There were 190 intersecting targets between GuizhiFuling Pill and chronic prostatitis.GO analysis indicated that Guizhi Fuling Pill may treat chronic prostatitis by participating in processes such asapoptosis,ATP binding,and signal transduction.KEGG analysis suggested that Guizhi Fuling Pill can regulate pathways such as phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)and mitogen-acti-vated protein kinase(MAPK)to intervene in chronic prostatitis.Molecular docking data demonstra-ted that the components of Guizhi Fuling pill exhibited stable conformations with their targets.Con-clusion The components of Guizhi Fuling Pill can stably bind to their targets and exert therapeutic effects on chronic prostatitis through multiple targets and pathways.

Objectives:To explore the predictive value of angiography-derived index of microcirculatory resistance(Angio-IMR)for early prognosis in patients with acute ST-segment elevation myocardial infarction(STEMI)after percutaneous coronary intervention(PCI).Methods:This multicenter study enrolled 1 629 consecutive STEMI patients who underwent successful PCI at three grade A tertiary hospitals(The Second Affiliated Hospital,Zhejiang University School of Medicine;Shengjing Hospital of China Medical University;Renji Hospital,Shanghai Jiao Tong University School of Medicine)from June 1,2017,to May 31,2020.According to postoperative Angio-IMR,patients was stratified into two groups:the Angio-IMR>40 group(n=508)and the Angio-IMR≤40 group(n=1 121).The incidence of major adverse cardiovascular events(MACE;defined as a composite endpoint including cardiac death,heart failure rehospitalization,cardiogenic shock,malignant arrhythmia,cardiopulmonary resuscitation and stent thrombosis)within 1-month post-PCI was compared between the two groups.Results:The median Angio-IMR after PCI was 32.4(22.3,42.6).The cumulative incidence of early-term MACE was significantly higher in patients with Angio-IMR>40,compared to those with Angio-IMR≤40(5.5%vs.2.3%,log-rank P<0.001).Multivariate Cox regression analysis showed that Angio-IMR>40 was an independent predictor of early-term MACE(HR=2.07,95%CI:1.20-3.58,P=0.009).The addition of Angio-IMR enhanced the predicting performance of the clinical risk model to predict early adverse outcomes(AUC:0.820 vs.0.794,P=0.043).Conclusions:In patients with STEMI after PCI,Angio-IMR can predict the occurrence of early-term MACE.The incorporation of Angio-IMR to clinical models significantly improves the model ability to predict early adverse outcomes in these patients.

Objectives:To explore the predictive value of angiography-derived index of microcirculatory resistance(Angio-IMR)for early prognosis in patients with acute ST-segment elevation myocardial infarction(STEMI)after percutaneous coronary intervention(PCI).Methods:This multicenter study enrolled 1 629 consecutive STEMI patients who underwent successful PCI at three grade A tertiary hospitals(The Second Affiliated Hospital,Zhejiang University School of Medicine;Shengjing Hospital of China Medical University;Renji Hospital,Shanghai Jiao Tong University School of Medicine)from June 1,2017,to May 31,2020.According to postoperative Angio-IMR,patients was stratified into two groups:the Angio-IMR>40 group(n=508)and the Angio-IMR≤40 group(n=1 121).The incidence of major adverse cardiovascular events(MACE;defined as a composite endpoint including cardiac death,heart failure rehospitalization,cardiogenic shock,malignant arrhythmia,cardiopulmonary resuscitation and stent thrombosis)within 1-month post-PCI was compared between the two groups.Results:The median Angio-IMR after PCI was 32.4(22.3,42.6).The cumulative incidence of early-term MACE was significantly higher in patients with Angio-IMR>40,compared to those with Angio-IMR≤40(5.5%vs.2.3%,log-rank P<0.001).Multivariate Cox regression analysis showed that Angio-IMR>40 was an independent predictor of early-term MACE(HR=2.07,95%CI:1.20-3.58,P=0.009).The addition of Angio-IMR enhanced the predicting performance of the clinical risk model to predict early adverse outcomes(AUC:0.820 vs.0.794,P=0.043).Conclusions:In patients with STEMI after PCI,Angio-IMR can predict the occurrence of early-term MACE.The incorporation of Angio-IMR to clinical models significantly improves the model ability to predict early adverse outcomes in these patients.

Objective To analyze and summarize the clinical presentation of spontaneous and secondary intracranial hypotension syndrome(IHS).Methods Patients diagnosed with spontaneous or secondary IHS from September 2022 to May 2023 were retrospectively analyzed.The clinical data,imaging features,treatment methods and prognosis were collected.The correlation between intracranial pressure values and clinical characteristics of the patients was statistically analyzed.Results A total of 30 patients were enrolled,and the proportion of spontaneous and secondary IHS was 63%(19 cases)and 37%(11 cases),respectively.In terms of clinical features,orthostatic headache was the most common type(29 cases,96.7%)and most commonly involved occipital region(12 cases,40.0%),followed by frontoparietal region(9 cases,30.0%).Among the brain imaging features,dural enhancement was the most common(17 cases,56.7%).According to CT angiography of spinal cord findings,cerebrospinal fluid leakage is one of the most common location of cervical spine segments(10 cases),and on the thoracic segments(9 cases),followed by the thoracic segments(4 cases)and lumbar segments(4 cases).After conservative treatment and surgical treatment,the total effective rate was 90%.Conclusion Orthostatic headache and cranial MRI"dural enhancement"have strong indication on the definitive diagnosis of IHS.CT myelography is helpful to precisely localize the site of cerebrospinal fluid leakage.Targeted epidural blood patch therapy is an effective method to cure IHS when conservative treatment is ineffective.

The current organ allocation rules prioritize elderly and urgent patients on the lung transplantation (LT) waiting list. A steady increase in the threshold at which age is taken into consideration for LT has been observed. This retrospective cohort study recruited 166 lung transplant recipients aged ≽ 65 years between January 2016 and October 2020 in the largest LT center in China. In the cohort, subgroups of patients aged 65-70 years (111 recipients, group 65-70) and ≽ 70 years (55 recipients, group ≽ 70) were included. Group D restrictive lung disease was the main indication of a lung transplant in recipients over 65 years. A significantly higher percentage of coronary artery stenosis was observed in the group ≽ 70 (30.9% vs. 14.4% in group 65-70, P = 0.014). ECMO bridging to LT was performed in 5.4% (group 65-70) and 7.3% (group ≽ 70) of patients. Kaplan-Meier estimates showed that recipients with cardiac abnormalities had a significantly increased risk of mortality. After adjusting for potential confounders, cardiac abnormality was shown to be independently associated with the increased risk of post-LT mortality (HR 6.37, P = 0.0060). Our result showed that LT can be performed in candidates with an advanced age and can provide life-extending benefits.
Aged ; Humans ; East Asian People ; Heart Diseases/etiology* ; Lung Transplantation/adverse effects* ; Retrospective Studies

Objective:To explore the effects of bariatric metabolic surgery on body composition.Methods:The retrospective cohort study was conducted. The clinicopathological data of 66 patients with metabolic diseases who were admitted to the Third Xiangya Hospital of Central South University from January 2013 to December 2014 were collected. There were 42 males and 24 females, aged (40±11)years, with a range from 17 to 63 years. Of the 66 patients, 27 undergoing laparoscopic sleeve gastrectomy (LSG) and 39 undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) were allocated into LSG group and LRYGB group, respectively. The body composition of all patients was determined by dual-energy X-ray absorptiometry at preoperation and postoperative 6 months. Observation indicators: (1) the changes of anthropometric parameters, glucolipid metabolism, body fat mass percentage (BF%) and the ratio of Android BF% and Gynoid BF% (A/G ratio) from preoperation to postoperative 6 months; (2) the changes of whole and local body composition from preoperation to postoperative 6 months; (3) analysis of the correlation between BF% and anthropometric parameters, glucolipid metabolism. (4) Follow-up. Follow-up was conducted using outpatient or hospitalization examination to detect the changes of body composition at the time of postoperative 6 month. The follow-up time was up to July 2015. Measurement data with normal distribution were represented as Mean± SD, paired-samples t test was used for intra-group comparison, and independent-samples t test when baseline data were consistency or covariance analysis when baseline data were not consistency was used for inter-group comparison. Measurement data with skewed distribution were represented as M ( P25, P75), and comparison between groups was analyzed using Wilcoxon signed rank test. The correlation test was undertaken with the Pearson bivariate analysis. Results:(1) The changes of anthropometric parameters, glucolipid metabolism, BF% and A/G ratio from preoperation to postoperative 6 months: for patients in the LSG group, the body mass, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), diastolic blood pressure (DBP), systolic blood pressure (SBP), fasting plasma glucose (FPG), HbA1c, high density lipoprotein cholesterol (HDL-C), triglyceride (TG), whole BF%, arms BF%, legs BF%, trunk BF%, Android BF%, Gynoid BF% and A/G ratio at preoperation and postoperative 6 months were (102±17)kg, (37±5)kg/m 2, (118±14)cm, 1.01±0.06, (94±14)mmHg(1 mmHg=0.133 kPa), (137±15)mmHg, (8.1±4.2)mmol/L, 7.3%±2.4%, (1.11±0.26)mmol/L, 2.14 mmol/L(1.73 mmol/L, 2.59 mmol/L), 40%±6%, 46%±10%, 36%±8%, 42%±6%, 45%±6%, 37%±7%, 1.23±0.18 and (82±15)kg, (29±4)kg/m 2, (101±13)cm, 0.95±0.08, (76±10)mmHg, (118±16)mmHg, (7.2±1.2)mmol/L, 5.4%±0.8%, (1.26±0.32)mmol/L, 1.21 mmol/L(0.88 mmol/L, 1.55 mmol/L), 36%±8%, 41%±9%, 34%±10%, 38%±8%, 41%±8%, 35%±10%, 1.20±0.17, respectively. There was no significant difference in the intra-group comparison of the Gynoid BF% and A/G ratio ( t=1.903, 1.730, P>0.05) and there were significant differences in the intra-group comparison of the rest of above indicators ( t=12.748, 13.283, 9.013, 3.804, 6.031, 6.226, 2.393, 4.287, -2.900, 3.193, 2.932, 5.198, 2.167, 3.357, 3.116, P<0.05). For patients in the LRYGB group, the body mass, BMI, WC, WHR, DBP, SBP, FPG, HbA1c, HDL-C, TG, whole BF%, arms BF%, legs BF%, trunk BF%, Android BF%, Gynoid BF% and A/G ratio at preoperation and postoperative 6 months were (80±12)kg, (28±4)kg/m 2, (98±9)cm, 0.96±0.05, (85±10)mmHg, (134±17)mmHg, (8.6±2.8)mmol/L, 8.3%±1.7%, (1.13±0.26)mmol/L, 2.06 mmol/L(1.15 mmol/L, 3.30 mmol/L), 30%±8%, 29%±11%, 23%±9%, 37%±7%, 40%±7%, 29%±8%, 1.42±0.26 and (69±9)kg, (24±3)kg/m 2, (91±8)cm, 0.93±0.05, (80±9)mmHg, (129±18)mmHg, (7.4±1.8)mmol/L, 7.0%±1.5%, (1.18±0.29)mmol/L, 1.29 mmol/L(0.85 mmol/L, 2.02 mmol/L), 25%±8%, 23%±12%, 20%±9%, 29%±9%, 32%±10%, 25%±9%, 1.29±0.25, respectively. There was no significant difference in the intra-group comparison of the SBP and HDL-C ( t=1.733, -1.073, P>0.05) and there were significant differences in the intra-group comparison of the rest of above indicators ( t=10.525, 10.200, 7.129, 2.887, 2.805, 2.517, 3.699, 2.608, 7.997, 8.018, 6.029, 8.342, 8.069, 5.813, 6.391, P<0.05). There were significant differences in DBP, SBP, HbA1c, trunk BF%, Android BF% and A/G ratio at postoperative 6 months between LSG group and LRYGB group ( F=6.408, t=2.641, F=20.673, 5.140, 5.735, 4.714, P<0.05). (2) The changes of whole and local body composition from preoperation to postoperative 6 months: for patients in the LSG group, the whole fat mass, muscle mass, fat-free mass at preoperation and postoperative 6 months were (38.74±9.68)kg, (57.71±11.62)kg, (60.14±11.95)kg and (26.64±8.29)kg, (48.65±13.80)kg, (51.00±14.27)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=5.256, 5.413, 5.315, P<0.05); the arms fat mass, muscle mass, fat-free mass were (5.19±1.67)kg, (5.78±1.58)kg, (6.10±1.64)kg and (3.73±1.19)kg, (5.10±1.53)kg, (5.43±1.57)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=7.564, 5.405, 5.363, P<0.05); the legs muscle mass and fat-free mass were (19.05±4.19)kg, (19.93±4.35)kg and (15.93±4.71)kg, (16.81±4.87)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=5.623, 5.568, P<0.05); the trunk fat mass and fat-free mass were (21.93±4.90)kg, (29.7±5.94)kg and (14.69±4.79)kg, (24.78±7.02)kg respectively, showing significant differences in the intra-group comparison of the above indicators ( t=8.903, 5.421, P<0.05); the Android fat mass and fat-free mass were (4.16±1.19)kg, (5.01±1.12)kg and (2.57±0.90)kg, (3.83±1.20)kg respectively, showing significant differences in the intra-group comparison of the above indicators ( t=8.288, 7.637, P<0.05); the Gynoid fat mass and fat-free mass were (5.51±1.42)kg, (9.27±1.86)kg and (3.85±1.16)kg, (7.65±2.31)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=7.461, 5.672, P<0.05); the skeletal muscle index were (8.86±1.38)kg/m 2 and (7.49±1.71)kg/m 2, respectively, showing a significant differences in the intra-group comparison ( t=5.724, P<0.05). For patients in the LRYGB group, the whole fat mass, muscle mass, bone mineral content, fat-free mass at preoperation and postoperative 6 months were (23.58±7.80)kg, (51.76±8.35)kg, (2.55±0.48)kg, (54.31±8.63)kg and (16.88±6.86)kg, (49.41±7.70)kg, (2.47±0.50)kg, (51.88±8.05)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=9.001, 3.974, 4.354, 4.075, P<0.05); the arms fat mass were (2.72±2.37)kg and (1.73±1.02)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=3.470, P<0.05); the legs fat mass, muscle mass, fat-free mass were (5.21±2.46)kg, (16.68±3.50)kg, (17.60±3.66)kg and (4.01±2.12)kg, (15.63±2.90)kg, (16.54±3.05)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=6.592, 3.372, 3.319, P<0.05); the trunk fat mass were (14.87±4.11)kg and (10.38±4.00)kg, respectively, showing a significant difference in the intra-group comparison of the above indicators ( t=8.431, P<0.05); the Android fat mass and fat-free mass were (2.61±0.86)kg, (3.96±0.87)kg and (1.81±0.79)kg, (3.78±0.67)kg respectively, showing significant differences in the intra-group comparison of the above indicators ( t=8.032, 2.153, P<0.05); the Gynoid fat mass and fat-free mass were (3.14±1.17)kg, (7.89±1.58)kg and (2.44±0.96)kg, (7.43±1.26)kg, respectively, showing significant differences in the intra-group comparison of the above indicators ( t=6.112, 3.207, P<0.05); the skeletal muscle index were (8.04±1.22)kg/m 2 and (7.43±1.13)kg/m 2, respectively, showing significant differences in the intra-group comparison ( t=4.953, P<0.05). There were significant differences in whole muscle mass, whole fat-free mass, arms fat mass, legs muscle mass, legs fat-free mass, trunk fat-free mass, Android fat-free mass, Gynoid fat-free mass and skeletal muscle index at postoperative 6 months between LSG group and LRYGB group ( F=13.846, 13.614, 23.696, 7.100, 7.127, 15.243, 16.921, 8.625, 5.497, P<0.05). (3) Analysis of the correlation between BF% and anthropometric parameters, glucolipid metabolism: the whole BF% of 66 patients was positively correlated with body mass, BMI, WC and WHR ( r=0.405, 0.663, 0.625, 0.331, P<0.05); the arms BF% was positively correlated with body mass, BMI, WC and WHR ( r=0.432, 0.682, 0.639, 0.309, P<0.05); the legs BF% was positively correlated with body mass, BMI and WC ( r=0.366, 0.646, 0.564, P<0.05); the trunk BF% was positively correlated with body mass, BMI, WC and WHR ( r=0.332, 0.560, 0.554, 0.335, P<0.05); the Android BF% was positively correlated with body mass, BMI, WC and WHR ( r=0.327, 0.537, 0.543, 0.336, P<0.05); the Gynoid BF% was positively correlated with BMI and WC ( r=0.561, 0.488, P<0.05), and negatively correlated with FPG ( r=-0.491, P<0.05); the A/G ratio was negatively correlated with BMI ( r=-0.334, P<0.05), and positively correlated with FPG ( r=0.506, P<0.05); the skeletal muscle index was positively correlated with body mass, BMI, WC and WHR ( r=0.757, 0.641, 0.609, 0.519, P<0.05), and negatively correlated with HDL-C ( r=-0.369, P<0.05). (4) Follow-up: 66 patients were followed up at the time of postoperative 6 month. Conclusions:Both LSG and LRYGB significantly change body composition. LRYGB is superior to LSG in reducing trunk BF% and Android BF%. The effects of the two surgical methods on fat mass and bone mineral content are similar. LSG lead to a more significant decrease in whole muscle mass, and LRYGB lead to a more significant decrease in legs muscle mass and skeletal muscle index.

OBJECTIVE: To develop a digital breast tomosynthesis (DBT) imaging system with optimizes imaging chain. METHODS: Based on 3D tomography and DBT imaging scanning, we analyzed the methods for projection data correction, geometric correction, projection enhancement, filter modulation, and image reconstruction, and established a hardware testing platform. In the experiment, the standard ACR phantom and high-resolution phantom were used to evaluate the system stability and noise level. The patient projection data of commercial equipment was used to test the effect of the imaging algorithm. RESULTS: In the high-resolution phantom study, the line pairs were clear without confusing artifacts in the images reconstructed with the geometric correction parameters. In ACR phantom study, the calcified foci, cysts, and fibrous structures were more clearly defined in the reconstructed images after filtering and modulation. The patient data study showed a high contrast between tissues, and the lesions were more clearly displayed in the reconstructed image. CONCLUSIONS This DBT imaging system can be used for mammary tomography with an image quality comparable to that of commercial DBT systems to facilitate imaging diagnosis of breast diseases.
Algorithms ; Artifacts ; Breast ; diagnostic imaging ; Female ; Humans ; Mammography ; methods ; Phantoms, Imaging ; Radiographic Image Enhancement ; methods

BACKGROUND: Bone exposed wounds are frequently required to deal with in orthopaedic surgeries, involving the treatment of open fractures, bone tumors, osteomyelitis, and many other diseases, in which the defect of soft tissue caused by open fractures is the most difficult to deal with. Conventional debridement or negative pressure closed drainage technology is difficult to make bone exposed wounds heal, and the process is extremely cumbersome, during which,patients suffer a lot of pain.OBJECTIVE: To evaluate the advantages and disadvantages of the various types of dressings, and review the application of new hydrogel dressing in bone exposed wounds based on its advantages, such as keeping wound environment moisture, restoring skin physical barrier, contributing to routine dressing change.METHODS: A computer-based online retrieval of PubMed and CNKI databases was performed to search papers published between 2000 and 2016 using the key words hydrogel dressing, bone exposed wound, traditional wound dressing, antibiotic in English and Chinese, respectively. A total of 55 papers suitable for final analysis from the application of traditional and new dressings in bone tissue engineering were reviewed.RESULTS AND CONCLUSION: The treatment of bone exposed wounds involves the treatment of many diseases, such as open fractures, bone tumors, osteomyelitis, which is still an orthopedic problem to solve. The novel hydrogel dressings with unique advantages are able to provide better plans for bone exposed wounds, and the use of these dressings solves the regeneration and repair of exposed bone, and improves the infection of antibiosis. In addition, the gel dressings currently have become a hot spot of research because of the characteristics of sustained-release.

Objective To investigate the safety and efficacy of decitabine combined with CAG regimen in treatment of acute myeloid leukemia (AML) ineligible for conventional chemotherapy. Methods The data of 20 cases with AML ineligible for conventional chemotherapy from January 2013 to May 2015 were retrospectively analyzed. Decitabine combined with CAG regimen was used during induction therapy. The primary induction regimen was used 26 times after remission, the standard 3+7 regimen were used 7 times, and intermediate-dose cytarabine were used 3 times. The total course of treatment included 2-8 cycles. Results All of the 20 patients completed the first cycle of induction therapy, including 11 cases of complete remission (CR), 5 cases of partial remission and no response in 4 cases, and the overall response rate (ORR) was 80 % (16/20). ORR was 69.2 % (9/13) and 100.0 % (7/7) in high-risk group and middle-low risk group respectively. ORR was 60.0%(6/10) in AML evolving from MDS. 8 patients were infected during the induction therapy and the infection rate was 40.0% (8/20). 2 patients were died of pulmonary infection. The median number of suspended red blood cell and platelet infused were (9.1±5.7) U and (57.5±51.9) U respectively. Neutrophil recovery time was (8.7±5.6) days during induction therapy. All patients were followed up for at least 1 year, and 12 cases were dead. Overall survival rate was 85.0%at 3 months, 80.0%at 6 months, and 40.0%at 1 year. While in 12 CR patients relapse-free survival rate was 75.0%at 3 months, 75.0%at 6 months,and 65.6%at 1 year respectively. Conclusion Decitabine combined with CAG regimen with high remission rate and well tolerance, can be used as a first therapy for AML ineligible for conventional chemotherapy.

Objective:To explore the quality of inventory samples of a biobank stored in a deep freezer from 0 to over 10 years in Shanghai Ruijin Hospital. Methods:We extracted 24 pairs of stocked gastric cancer samples between 2003 and 2014. We used 1%aga-rose gel electrophoresis to analyze DNA and RNA purity and integrity while adding the RNA integrity number (RIN) for precise analysis. Bicinchonininc acid (BCA) assay was used for protein concentration evaluation. Coomassie brilliant blue method was used for protein integrity assay. Results: The samples were divided into four groups according to cryopreservation period (<2 years, 3-5 years, 6-8 years, and>9 years). No significant difference in DNA integrity was found between the groups (P>0.05);however, DNA degradation in normal gastric mucosa was faster than that in gastric cancer tissue (P=0.023). The RIN significantly declined when the storage period was 6 years or longer (P=0.018). No significant difference in protein concentration was observed between different groups. Using Coo-massie brilliant blue method, we found significant differences in preserved proteins with different molecular weights. Proteins with varying molecular weights were detected in the groups with the following cryopreservation periods:>9 years, a small number of low-molecular-weight (average 36.5 KD) proteins;6-8 years, medium-molecular-weight (average 65.63KD) proteins;3-5 years, high-molecu-lar-weight (average 127.5 KD) proteins;<2 years, high-molecular-weight (average 160 KD) proteins. Conclusion:Cryopreservation does not exert an obvious effect on DNA. If the cryopreservation period is more than 5 years, serious degradation of RNA should occur;like-wise, degradation of proteins with higher molecular weight should occur.