Drug discovery of sclerostin inhibitors

Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA, the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis; however, it conferred high cardiovascular risk in clinical trials. Furthermore, romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.

Anthelmintics nitazoxanide protects against experimental hyperlipidemia and hepatic steatosis in hamsters and mice

Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in Apoe -/- mice. The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.

Correlation of isokinetic thigh muscle asymmetry with gait asymmetry at one year after anterior cruciate ligament reconstruction / 中华创伤杂志

Objective:To investigate the correlation of isokinetic thigh muscle asymmetry with gait asymmetry at one year after anterior cruciate ligament (ACL) reconstruction.Methods:A retrospective case series analysis was made on 25 patients treated by ACL reconstruction in Third Hospital of Peking University from January 2014 to January 2019. All the subjects were male, aged 17-47 years [(29.4±5.2)years]. Standard rehabilitation treatment procedures were conducted after surgery. The isokinetic muscle strength of the thigh was collected at one year after operation to evaluate knee extensor and flexor concentric strength at 60°/s, 180°/s and 300°/s, and knee extensor and flexor eccentric strength at 60°/s. The maximum concentric and eccentric strength of the knee extensor and flexor were analysed between the injured and intact side. The three-dimensional motion information and ground reaction force was collected during the stance phase of gait, and knee kinematic and kinetic parameters were calculated by inverse dynamics analysis, including the peak flexion moment, peak extension moment, first and second peak adduction moment, peak external and internal rotation moment, peak flexion angle, peak extension angle during the terminal stance phase, flexion angle at heel strike, peak abduction angle, and peak external rotation angle during terminal stance phase. Spearman correlation analysis was used to study the correlation between limb symmetry index (LSI) of isokinetic muscle strength and LSI of gait parameters.Results:One year after ACL reconstruction, the maximum concentric strength of the knee extensor and flexor at 60°/s, 180°/s and 300°/s and maximum eccentric strength of the knee flexor and extensor at 60°/s on the injured side were significantly lower than those on the normal side (all P<0.01). Compared with the intact side, the peak knee extension moment on the injured side was significantly lower during the stance phase of gait ( P<0.01), and the extension angle was insufficient during the terminal stance phase ( P<0.01). There were no significant differences between the injured and intact side in terms of peak flexion moment, first and second peak adduction moment, peak external and internal rotation moment, peak flexion angle, flexion angle at heel strike, peak abduction angle, and peak external rotation angle during terminal stance phase (all P>0.05). One year after ACL reconstruction, Spearman correlation analysis during gait stance phase showed that the LSI of 60°/s concentric strength of the isokinetic knee extensor was significantly related to LSI of peak internal rotation moment ( R=0.42, P<0.05), the LSI of 180°/s concentric strength of the isokinetic knee extensor was significantly related to LSI of peak flexion moment ( R=0.45, P<0.05), the LSI of 180°/s concentric strength of the isokinetic knee flexor was significantly correlated with LSI of peak flexion angle ( R=0.46, P<0.05), the LSI of 300°/s concentric strength of the isokinetic knee extensor was significantly correlated with LSI of peak knee flexion angle ( R=0.42, P<0.05), and the LSI of 60°/s eccentric strength of the isokinetic flexor was significantly correlated with LSI of peak knee flexion angle ( R=0.54, P<0.01). Conclusions:For patients following ACL reconstruction at one year postoperatively, a significant correlation of isokinetic thigh extensor strength asymmetry with peak knee flexion and rotation moment and peak knee flexion angle, and that of isokinetic thigh flexor strength asymmetry with peak knee flexion angle are observed during the stance phase of gait, which suggests that patients with ACL reconstruction still need systematic rehabilitation training one year postoperatively to improve muscle strength and motor function so as to reduce the risk of ACL reinjury and secondary injury.

Relationship between serum claudin-1 level and papillary thyroid carcinoma / 中华内分泌代谢杂志

Objective:To analyze the correlation between serum claudin-1(Cla-1) level and the risk of papillary thyroid carcinoma(PTC) in patients with thyroid nodules.Methods:The clinical data of 345 patients with thyroid nodules were retrospectively analyzed. According to the pathological results, they were divided into PTC group and benign thyroid nodule(BTN) group. The difference of serum Cla-1 level between 2 groups and its correlation with the risk of PTC were analyzed.Results:In groups of PTC( n=225) and BTN( n=120), the median value of serum Cla-1 level was 14.03(10.30, 20.40) ng/mL. The differences in the median value[17.90(14.00, 22.93)ng/mL vs 9.40(8.15, 11.20) ng/mL] of serum Cla-1 level in the PTC and BTN were statistically significant by Wilcoxon signed-rank test. The prevalence of PTC in thyroid nodules increased gradually with increasing of serum Cla-1 level. Receiver operated characteristic curve analysis showed that the best diagnostic cut-off value of the PTC was 13.02 ng/ml of which the sensitivity was 81.8%, the specificity was 89.2%, and the area under curve(AUC) was the largest(AUC=0.944, P<0.01, 95% CI 0.922-0.965). Logistic regression analysis showed that elevated serum Cla-1 level increased the risk of PTC, and it was statistically significant( OR=4.334, 95% CI 1.662-11.303, P=0.003). There was a significant correlation among the serum Cla-1 level and gender, age, location of involvement, number and diameter of cancer nodules, extracapsular invasion of thyroid, lymph node metastasis, tumor stage and combined with Hashimoto′s thyroiditis( P<0.01). Conclusion:The serum level of Cla-1 may be one of risk factors to predict PTC, and it is related to the total amount of PTC tumor cells in vivo, but it was not related to the aggressive behavior of tumor.

Lipids, Anthropometric Measures, Smoking and Physical Activity Mediate the Causal Pathway From Education to Breast Cancer in Women: A Mendelian Randomization Study / 한국유방암학회지

Purpose@#We aimed to investigate whether obtaining a higher level of education was causally associated with lower breast cancer risk and to identify the causal mechanism linking them. @*Methods@#The main data analysis used publicly available summary-level data from 2 large genome-wide association study consortia. Mendelian randomization (MR) analysis used 65 genetic variants derived from the Social Science Genetic Association Consortium as instrumental variables for years of schooling. The outcomes from the Breast Cancer Association Consortium (BCAC) were the overall breast cancer risk (122,977 cases/105,974 controls in women) and the two subtypes: estrogen receptor (ER)-positive breast cancer and ER-negative breast cancer. Fixed and random effects inverse variance weighted methods were used to estimate the causal effects, along with other additional MR methods for sensitivity analyses. @*Results@#Results showed that each additional standard deviation of 4.2 years of education was causally associated with a 27% lower risk of ER-negative breast cancer (odds ratio, 0.73; 95% confidence interval, 0.64–0.84; p-value 10 minutes explain a small part of the causal effect of education on the risk of developing breast cancer, and their mediation proportion is approximately 1%. @*Conclusion@#A low level of education is a causal risk factor in the development of breast cancer as it is associated with poor lipid profile, obesity, smoking, and types of physical activity.

Pulmonary alveolar regrowth in an adult COVID-19 patient

We detected active alveolar regrowth in the lung of a 58-year-old COVID-19 patient who underwent lung transplantation due to severe lung hemorrhage. Specifically, immunohistological and scanning electronic microscopy analyses revealed that alveolar type II epithelial cells (AT2 cells) accumulate in response to viral pneumonia and that these AT2 cells actively proliferate and differentiate into squamous AT1-like alveolar epithelial cells. Thus, our work establishes that alveolar regrowth does occur in post-COVID-19 injury adult human lungs.

Follow-up testing of viral nucleic acid in discharged patients with moderate type of 2019 coronavirus disease (COVID-19) / 浙江大学学报·医学版

OBJECTIVE@#To investigate the clinical outcome of patients with moderate type of corona virus disease 2019 (COVID-19) after discharge by retesting viral nucleic acid.@*METHODS@#Seven patients with moderate COVID-19 met the discharge criteria enacted by National Health Commission were quarantine in hospital for 7 days, then continuously quarantined at home for 4 weeks after discharged. During the three weeks of quarantined period, the symptoms and signs were documented; and sputum or nasal swab and feces samples were collected to test SARS-COV-2 nucleic acid by RT-PCR method.@*RESULTS@#There were no symptoms and signs during the quarantine period in all 7 patients. However, respiratory swabs from 3 patients were confirmed positive of SARS-COV-2 nucleic acid at 5 to 7 days after they met the discharge criteria.@*CONCLUSIONS@#The study indicates that there is a relatively high incidence of positive viral nucleic acid in patients met the discharge criteria, and it is suggested that patients met the current discharge criteria should be quarantined in hospital for another 7 days and the follow-up viral testing is necessary.

Follow-up testing of viral nucleic acid in discharged patients with moderate type of COVID-19 / 浙江大学学报·医学版

OBJECTIVE@#To investigate the clinical outcome of patients with moderate type of coronavirus disease 2019 (COVID-19) after discharge by retesting viral nucleic acid.@*METHODS@#Seven patients with moderate COVID-19 met the discharge criteria enacted by National Health Commission were quarantined in hospital for 7 days, then continuously quarantined at home for 4 weeks after discharged. During the quarantined period, the symptoms and signs were documented, and sputum or nasal swab and feces samples were collected to test SARS-CoV-2 nucleic acid by RT-PCR method.@*RESULTS@#There was no symptoms and signs during the quarantine period in all 7 patients. However, respiratory swabs from 3 patients were confirmed positive of SARS-CoV-2 nucleic acid at 5 to 7 days after they met the discharge criteria.@*CONCLUSIONS@#There is a relatively high incidence of positive viral nucleic acid in patients met the discharge criteria, and it is suggested that patients met the current discharge criteria should be quarantined in hospital for another 7 days and the follow-up viral testing is necessary.

Effect of electro-acupuncture preconditioning on expression of protein kinase R-like endoplasmic reticulum kinase in hippocampus of mice following cerebral ischemia-reperfusion / 中华麻醉学杂志

Objective To evaluate the effect of electro-acupuncture preconditioning on the expression of protein kinase R-like endoplasmic reticulum kinase (PERK) in the hippocampus of mice following cerebral ischemia-reperfusion (I/R).Methods A total of 120 healthy male C56BL/6 mice,aged 7 weeks,weighing 20-30 g,were divided into 3 groups (n=40 each) using a random number table method:sham operation group (group S),cerebral I/R group (group I/R) and electro-acupuncture preconditioning group (group EA).Cerebral I/R was induced by clamping bilateral common carotid arteries for 15min followed by restoring cerebral blood flow in anesthetized mice.Dazhui and Baihui acupoints were stimulated with disperse-dense waves of 1 mA for 30 min once a day,lasting for 5 consecutive days,and cerebral I/R model was established at 24 h after the last stimulation in group EA.Animals were sacrificed at 24and 48 h of reperfusion,brains were removed,and hippocampi were isolated for determination of apoptotic neurons in hippocampal CAl region (by TUNEL) and expression of PERK (by Western blot).Results Compared with group S,the neurological deficit score and the number of apoptotic neurons in hippocampal CAl region were significantly increased at each time point of reperfusion in I/R and EA groups (P＜0.05).Compared with group I/R,the neurological deficit score and the number of apoptotic neurons in hippocampal CAl region were significantly decreased at each time point of reperfusion in group EA (P＜0.05).Conclusion The mechanism by which electro-acupuncture preconditioning mitigates endoplasmic reticulum stress during cerebral I/R may be related to inhibiting PERK activity in mice.

Effect of different approaches to thoracolumbar interfascial plane block on analgesic efficacy after lumbar spinal fusion / 中华麻醉学杂志

Objective To evaluate the effect of different approaches to thoracolumbar interfascial plane (TLIP) block on the analgesic efficacy after lumbar spinal fusion.Methods Seventy-five patients of both sexes,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,aged 40-70 yr,with body mass index ≤40 kg/m2,undergoing posterior median approach to lumbar spinal fusion,were divided into 3 groups (n =25 each) using a random number table method:patient-controlled intravenous analgesia (PCIA) group (group P),medial approach to TLIP combined with PCIA group (group MP) and lateral approach to TLIP combined with PCIA group (group LP).TLIP block was performed by advancing the block needle in a lateral to medial direction and injecting 0.5％ ropivacaine 20 ml locally between the bilateral multifidus and longissimus muscles in group MP.TLIP block was performed by advancing the block needle in a medial to lateral direction and injecting 0.5％ ropivacaine 20 ml locally between the bilateral longissimus and iliocostalis muscles in group LP.The identification rate and distinction score between multifidus and iliocostalis muscles obtained from ultrasonic images were recorded before block in MP and LP groups.All the patients received PCIA until 48 h after surgery.PCIA solution contained sufentanil 100 μg and tropisetron 10 mg diluted to 100 ml with 0.9％ normal saline.The PCA pump was set up with a 2 ml bolus dose,a 15-min lockout interval and background infusion at a rate of 1 ml/h.When visual analogue scale score at rest ＞4 after surgery,parecoxib 40 mg was intravenously injected for rescue analgesia.The development of adverse reactions such as nausea and vomiting was recorded within 48 h after surgery.Results The identification rate and distinction score of the iliocostalis was significantly higher than that of the multifidus (P＜0.05).Compared with group P,the intraoperative consumption of propofol and remifentanil was significantly decreased,the pressing times of PCA,amount of drugs consumed in PCA and consumption of parecoxib were decreased within 48 h after surgery (P＜0.05),and no significant change was found in the incidence of nausea or vomiting in MP and LP groups (P＞0.05).There was no significant difference in the parameters mentioned above between group MP and group LP (P＞0.05).Conclusion Ultrasound-guided medial and lateral approaches to TLIP block is helpful in achieving low-dose opioid anesthesia mode and more helpful in enhancing the efficacy of PCIA when used for lumbar spinal fusion.

Characteristics of clinicopathology and immunohistochemical molecular markers of 92 cases of heterotopic pancreas in upper gastrointestinal tract / 中华消化杂志

Objective To investigate the clinicopathological characteristics and the expression of related molecular markers of heterotopic pancreas for better understanding and avoiding overtreatment of this disease.Methods From 24th March 2009 to 10th November 2016,92 patients with heterotopic pancreas in upper digestive tract diagnosed after endoscopic submucosal dissection(ESD),were collected. Tissues were sectioned and pathologically classified by Heinrich classification.The expressions of seven different molecular markers including cytokeratin(CK)19,insulin,trypsin,Ki-67,p53,CD133 and CD56 were detected by immunohistochemistry staining. Clinical features, pathological features and immunohistochemical results were retrospectively analyzed.Analysis of variance and Kruskal-Wallis test were used.Results According to Heinrich classification,the percentages of type Ⅰ,Ⅱ,and Ⅲ of heterotopic pancreas were 27.2%(25/92),63.0%(58/92)and 9.8%(9/92),respectively.There was no type Ⅳ patients.The heterotopic pancreas mainly located in stomach with proportion being about 91.3%(84/92)of the total heterotopic pancreas.CK19(the marker of pancreas ducts),insulin(as marker of endocrine function)and trypsin(as the marker of exocrine function)were all expressed in heterotopic pancreas.The positive rate of CD56,a pancreatic neuroendocrine marker,was 66.3%(61/92).The umbilicus like depression was the typical endoscopic appearance of heterotopic pancreas,which only found in 29 patients(31.5%).The average rate of Ki-67,cell proliferation index,was(2.08 ± 1.41)%.The expression of mutant p53 was negative in all 92 cases of heterotopic pancreas.The average staining area of CD133,a marker of pancreatic cancer stem cell,was(2.53 ± 2.43)%.The average follow-up period of 92 patients was(43.6 ± 27.5)months.No relapse and malignant change were found and all patients survived after ESD.Conclusions Heterotopic pancreas has normal pancreatic construction and function.The cell proliferation index is low in heterotopic pancreas and no mutant p53 expression is found.The expression of CD133 is also low.Heterotopic pancreas is a congenital benign disease which requires a long-term follow-up rather than overtreatment.

Development and application of holding mechanism for drainage bag / 医疗卫生装备

Objective To develop a holding mechanism for the drainage bag to reduce the accident rate of tube falling off during CT examination.Methods The mechanism was composed of a bed body,a mobile bed board,a connecting board,a rod and kink section.CT bed board had a sandwich structure with carbon fibre composite and foam material,and the connecting board,kink section,rod and its hinge joint were made of polycarbonate material.Results The mechanism decreased the risk for tube falling off during CT examination and increased the patient comfort.Conclusion The mechanism gains advantages in stability,mobility,convenience and practicability,and thus is worthy promoting practically.

Gait Analysis of Anterior Cruciate Ligament Deficient Patients with or Without Meniscus Injury / 中国运动医学杂志

Objective To identify the differences of three-dimensional knee kinematics of unilateral anterior cruciate ligament (ACL) deficient patients with and without the meniscus injury.Methods A total of 39 subjects including unilateral isolate ACL-deficient patients (ACL group,n=13),ACL deficient patients combined with meniscus tear (ACL+M group,n=13) and healthy controls (C group,n=13) participated in this study.In the gait analysis,three-dimensional knee kinematic and kinetic parameters were collected synchronously and compared.Results The peak knee flexion angles were greater in the ACL+M group and C group compared with the ACL group (P=0.001,P=0.001),with no significant differences between the former two groups (P=0.847).Lower first peak vertical ground reaction force,peak posterior ground reaction force,sagittal plane knee excursions and peak knee extension moment were found in ACL-injured side compared with the contralateral side (P=0.001,P＜0.001,P=0.006,P=0.001).Greater peak knee abduction moment was found in group ACL+M compared with both the ACL and C groups (P=0.045,P=0.014).However,no significant difference was observed between the ACL group and C group in peak knee abduction moment (P=0.616).Conclusions The altered loading in unilateral ACL deficient patients can lead to lower ground reaction force in injured knee and greater ground reaction force in the contralateral side,which may increase the risk of developing knee osteoarthritis.The greater internal knee abduction moment in ACL deficient patients combined with meniscus injury may be a risking factor for the knee osteoarthritis.

Therapeutic value of EUS-guided dehydrated ethanol lavage for pancreatic cystic neoplasms / 中华消化内镜杂志

Objective To evaluate the safety and feasibility of endoscopic ultrasonography(EUS)-guided dehydrated ethanol lavage on treatment of pancreatic cystic neoplasms(PCN). Methods The data of 15 patients with PCN treated by EUS-guided dehydrated ethanol lavage in Nanjing Drum Tower Hospital from April 2014 to December 2016 were retrospectively analyzed. All the patients underwent EUS-guided fine needle aspiration, and then the cyst cavity was lavaged with dehydrated ethanol. The curative effects and complications were evaluated after the procedure. Results Each patient had one operation and all the operations were successful. No operation-related intraoperative or postoperative complications occurred. Patients were followed up for a median time of 15 months(range from 3-30 months).Twelve patients finished a long term follow-up,including 6 cases of complete remission and 6 cases of partly remission. None of the patients underwent surgical resection. Conclusion Dehydrated ethanol lavage is safe and feasible for treatment of PCN.

Malignant progression and survival analysis for intraductal papillary mucinous neoplasms based on risk stratification / 中华消化内镜杂志

Objective To evaluate the potential malignancy, prognosis and risk factors for intraductal papillary mucinous neoplasm(IPMN), which were classified into different risk levels based on Fukuoka guideline. Methods A retrospective analysis of patients with IPMN diagnosed at Nanjing Drum Tower Hospital from 2009 to 2016 was conducted. Clinical characteristics,treatment and prognosis of IPMNs were analyzed. Results A total of 94 IPMN patients were included and divided into 3 groups according to Fukuoka guideline,46 patients in high-risk(HR)group,30 in group of worrisome features(WF), and 18 in low-risk(LR)group. For patients undergoing surgery treatment, there were 5 cases(19.2%,5/26)in HR group and 2 cases(12.5%,2/16)in WF group whose postoperative pathological findings were malignant (P=0.690). The 5-year survival rates after operations were 73.9% and 77.0% in HR and WF group, respectively(P=0.830). For patients without surgery treatment, in a 5-year follow-up, there were 6 cases (33.3%,6/18),2 cases(16.7%,2/12)and 0(0.0%,0/18)progressing into pancreatic cancers in HR, WF and LR groups,respectively(P<0.05). In addition,among the three groups,the 5-year survival rates were 49.5%,85.7% and 100.0%(P=0.025). Jaundice was significantly related to prognosis(P<0.01) and the hazard ratio was 8.883(95%CI:2.953-26.721). Conclusion Jaundice is a predictive risk factor for survival of IPMN. As for the treatment to IPMN, patients in HR group should receive surgery treatment while those in LR group can be followed up. For patients in WF group,the treatment should be customized, with evaluation of predictive risk factors,and operations can be performed when needed.

Serum levels of ANP signaling in different degree of allergic asthmatics and its role in the pathogenesis of allergic asthma / 中南大学学报(医学版)

OBJECTIVE@#To investigate the relationship between the severity of allergic asthma and the levels of atrial natriuretic peptide (ANP), and to analyze the potential role of ANP signaling in the pathogenesis of asthma.
@*METHODS@#We recruited 96 subjects, including 23 healthy volunteers, 25 stable allergic asthmatics, 21 mild allergic asthmatics and 27 moderate allergic asthmatics, from the Affiliated Hospital of Guilin Medical University. ANP, IFN-γ and IL-4 levels in serum were detected by enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein expressions of natriuretic peptide receptor A (NPRA), transcription factor T-bet and GATA3 were measured by RT-PCR and Western blot.
@*RESULTS@#The levels of ANP in serum and the expressions of NPRA mRNA and protein in the peripheral blood mononuclear cell (PBMC) from the mild asthma group or the moderate group were elevated compared with those in the stable asthma group or the mild group, respectively (P<0.05). Consistently, expressions of GATA3 and levels of IL-4 showed the same tendency (P<0.05). In addition, levels of ANP in serum were positively correlated with the severity of asthma, whereas negatively correlated with the ratio of T-bet/GATA3 and IFN-γ/IL-4 (r=-0.85, P<0.05; r=-0.88, P<0.05, respectively).
@*CONCLUSION@#Levels of ANP signaling in serum were significantly increased with the severity of allergic asthma, suggesting a close relation with the pathogenesis of asthma; ANP signaling may play a role in the pathogenesis of allergic asthma through inducing the Th2-type immune response.

Expressions of CA19-9, CA15-3 and CA125 and their significance in papillary thyroid carcinoma / 天津医药

Objective To investigate the expressions of carbohydrate antigen 19-9(CA19-9), carbohydrate antigen 15-3(CA15-3) and carbohydrate antigen 125(CA125) and their clinical significance in papillary thyroid carcinoma (PTC). Methods The expressions of CA19-9, CA15-3 and CA125 were detected by immunohistochemical MaxVision method in 80 cases of PTC and 80 cases of benign thyroid lesions (BTL), including 34 cases of nodular goiter, 26 cases of Hashimoto's thyroiditis and 20 cases of follicular adenoma. The relationship between expressions of CA19-9, CA15-3 and CA125 and the clinical pathological characteristics were analyzed. Results The expression rates of CA19-9, CA15-3 and CA125 in 80 cases of PTC were 85%, 100%and 43.8%respectively, compared with BTL, the difference was statistically significant (P 0.05). The sensitivity of CA19-9, CA15-3 and CA125 in the differential diagnosis of PTC and BTL were 85%, 100% and 43.8% respectively, and the specificity were 91.3%, 36.3%and 91.3%, respectively. Conclusion The expressions of CA19-9, CA153 and CA125 are helpful for the differential diagnosis of PTC and BTL.

Novel combination approaches for myeloma:reports from the 57th American Society of Hematology annual meeting / 白血病·淋巴瘤

As understanding the biology of multiple myeloma (MM) and application of new drugs, regimens containing new drugs deepened therapeutic response and prolonged the survival of MM patients. This article updates the therapeutic response of regimens reported in the 57th American Society of Hematology annual meeting, containing immunomodulatory agents, proteasome inhibitors, histone deacetylase inhibitors and other new drugs including monoclonal antibodies and the others. In the same time, minimal residual disease (MRD) is also used to evaluate the remission depth of MM. In order to achieve durable long-term remission and higher quality of life, new drug combination regimens have been recommended, especially for the relapsed or the high risk MM patients.

Effect of anterior cruciate ligament rupture on hamstring∶quadriceps ratio during isokinetic knee extension and flexion at 30 degrees of flexion / 北京大学学报(医学版)

Objective:To evaluate the change in hamstring ( H ):quadriceps ( Q ) ratio following anterior cruciate ligament ( ACL) rupture during isokinetic knee extension and flexion at 30 degrees of flexion which is important for knee dynamic function .Methods:A study was performed in 25 male com-plete unilateral ACL ruptures .Isokinetic concentric and eccentric quadriceps and hamstring muscle tests in both the deficient knees and intact knees were performed at 60°/s, respectively.At 30 degrees of flexion, the average torque of quadriceps and hamstring , Qe∶Qc ratios ( ratios of eccentric quadriceps to concentric quadriceps muscle torque ) , He∶Hc ratios ( eccentric hamstring to concentric hamstring ) , Hc∶Qc ratios ( concentric hamstring to concentric quadriceps ) , He∶Qc ratios ( eccentric hamstring to con-centric quadriceps ) , and Hc∶Qe ratios ( concentric hamstring to eccentric quadriceps ) were calculated . Wilcoxon matched-pairs signed-ranks test was used .Results:At 30 degrees of knee flexion , a significant reduction ( P<0.05) in the average torque of quadriceps was observed at concentric and eccentric 60°/s produced by the deficient-side compared with the intact side .In addition, Hc∶Qc, He∶Qc, and Qe∶Qc significantly increased on the ACL-deficient side .Conclusion:The change in H ∶Q ratio in the mode of isokinetic 60 °/s at 30 degrees of knee flexion might therefore be a new tool to objectively document muscle function in ACL-deficient knee .

New insights into the biology and clinical progress of multiple myeloma : reports from the 56th American Society of Hematology annual meeting / 白血病·淋巴瘤

Multiple myeloma (MM) is a unique cancer paradigm for investigating the mechanisms involved in the transformation from a premalignant condition (unknown monoclonal gamma globulin,MGUS) into a malignant disease (MM).In its pathogenesis,genotype characteristics of tumor clones which are highly complex and heterogeneous,as well as the dialogue between plasma cells and their microenvironment are equally important and both play a key role in the outcome of the disease.MM will soon no longer be considered as a single disease.A large number of new drug emergence and applications will increase the need for monitoring minimal residual disease (MRD) in prognosis and treatment of MM.New drugs and high-dose chemotherapy with autologous stem cell transplantation applications have been significantly improving the prognosis of MM in the past 20 years.Re-examining the early MM diagnostic criteria and the possibility of early intervention will open up a new therapeutic approach.It is important to find a balance of efficacy,toxicity and cost in order to achieve a cure for this disease.