[Comparison of the efficacy of carelizumab combined with chemotherapy and chemotherapy alone in the induction therapy of locally advanced hypopharyngeal carcinoma].

Objective: To compare the efficacy and safety of carrelizumab combined with the modified TPF regimen (docetaxel, cisplatinand capecitabine) and TPF regimen alone in larynx preservation strategy for locally advanced resectable hypopharyngeal squamous cell carcinoma. Methods: A cohort study was conducted. Patients with locally advanced resectable hypopharyngeal carcinoma (cT3-4aN0-3bM0) who were treated at the Eye & ENT Hospital of Fudan University from January 2017 to April 2023 were enrolled in the study. One group was treated with a modified TPF regimen (TPF group) for 2-3 cycles (retrospective data), and the other group was a prospective phase Ⅱ trial with a modified TPF regimen combined with carrelizumab (TPFC group) for three cycles. The patients with complete or partial remission of the primary focus were treated with sequential radical radiotherapy and/or drug therapy. The patients in the TPFC group were treated with carrelizumab at the end of radiotherapy with a maximum of up to 18 doses. The patients with stable or progressive disease were given radical surgery, and those who refused the surgery were given radical chemoradiotherapy. Objective response rate (ORR), overall survival rate, progression-free survival (PFS) rate, larynx preservation rate (LPR), and adverse reactions were compared between the two groups. Results: There were 51 male patients in the TPFC group, with an median age of 57 (35, 69) years. Meanwhile, 44 patients were in the TPF group, among which 43 were male and one was female, with an median age of 62 (46, 70) years. The ORR of the TPFC group was higher than that of the TPF group [82.4% (42/51) vs 63.6% (28/44), P=0.039]. During a median follow-up of 24.4 (18.5, 31.4) months, the TPFC group showed a higher 2-year survival rate (84.8% vs 64.6%, P=0.013) and 2-year LPR (66.6% vs 48.6%, P=0.045) than those in the TPF group. In patients with poor effect of induction therapy for hypopharyngeal carcinoma, surgical combination therapy significantly prolonged the 2-year PFS rate (77.9% vs 18.2%, P<0.001) and 2-year survival rate (76.9% vs 45.5%, P=0.005)than those of non-surgical combination therapy. The incidences of nausea and/or vomiting, reactive cutaneous capillary endothelial proliferation, thyroid dysfunction, and rash were increased in the TPFC group (all P<0.05). There was no treatment-related death. Conclusion: Carrelizumab combined with a modified TPF regimen has good efficacy and safety and can improve the LPR of locally advanced hypopharyngeal carcinoma.

[Relationship between plasma levels of thrombin activatable fibrinolysis inhibitor, plasminogen activator inhibitor-1 and tissue-type plasminogen activator and deep venous thrombosis in patients with systemic lupus erythematosus].

Objective: To investigate the plasma levels of thrombin activatable fibrinolysis inhibitor (TAFI), plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) in patients with systemic lupus erythematosus (SLE), and their relationship with deep venous thrombosis of the lower limbs. Methods: A case-control study was conducted to retrospectively select 32 SLE patients with deep venous thrombosis of the lower extremities (thrombus group) admitted to Liaocheng People's Hospital in Shandong Province from June 2018 to June 2021, including 4 males and 28 females, with a mean age of (49.7±5.5) years. Meanwhile, 64 SLE patients without deep venous thrombosis of the lower extremities (control group) were also selected, including 11 males and 53 females, with a mean age of (50.8±5.5) years. The plasma levels of TAFI, PAI-1 and t-PA of the two groups were compared. A logistic regression model was used to analyze the correlation of TAFI, PAI-1 and t-PA with SLE in patients. Results: The plasma levels of TAFI, PAI-1 and t-PA were (32.77±5.17) mg/L, (29.43±5.51) µg/L and (6.58±1.40) µg/L in the thrombotic group, while the plasma levels of TAFI, PAI-1 and t-PA in the control group were (23.56±4.40) mg/L, (19.00±4.40) µg/L and (9.40±2.23) µg/L. The levels of TAFI and PAI-1 in the thrombotic group were higher than those in the control group, while the level of t-PA was lower than that in the control group (all P<0.05). The results of logistic regression model showed that higher TAFI levels (OR=1.75, 95%CI: 1.05-2.90, P=0.043), higher PAI-1 levels (OR=1.85, 95%CI: 1.04-3.29, P=0.046), and lower t-PA levels (OR=0.72, 95%CI: 0.52-0.99, P=0.048) were related factors for the occurrence of deep venous thrombosis of the lower limbs in SLE patients. Conclusion: The plasma levels of TAFI and PAI-1 in SLE patients with deep venous thrombosis of the lower extremities increase, while the t-PA level decreases, which are related factors for the occurrence of deep venous thrombosis of the lower extremities in SLE patients.

RNA interference in Pardosa pseudoannulata, an important predatory enemy against several insect pests, through ingestion of dsRNA-expressing Escherichia coli.

RNA interference is an important technology for gene functional research in many organisms. The pond wolf spider (Pardosa pseudoannulata) is an important natural enemy of rice field pests. To facilitate large-scale gene functional research in this spider species and others, we developed an RNA interference (RNAi) method via ingestion of bacteria expressing dsRNA. The dsRNA targeting a cytochrome P450 monooxygenase (cyp41g2) was expressed in Escherichia coli HT115 (DE3). And then the bacterial suspension was fed to 14-20 days old spiderlings. The mRNA abundance of the target gene was significantly reduced after 3-day's ingestion of bacteria expressing dsRNA, and between day 5 and 7, RNAi efficiency remained stable. Thus, we selected 5 days as the optimum interference time. Furthermore, the bacteria resuspension containing 20 ng/µl dsRNA was selected as the optimum concentration. To evaluate the applicability of this method, three other genes with different tissue expression pattern were also selected as targets. And the mRNA abundance of all the four target genes was significantly reduced with RNAi efficiency between 66.0% and up to 86.9%. The results demonstrated that the oral delivery of bacteria expressing dsRNA would be an effective RNAi method for the gene functional study in P. pseudoannulata.

[Comparison of efficacy and safety of insulin aspart injection Rishulin and NovoRapid for treatment of diabetes: a multicenter, randomized, open-labeled, controlled trial].

Objective: To compare the efficacy and safety of Tonghua Dongbao's insulin aspart injection (Rishulin) and NovoRapid (Novo Nordisk) in the treatment of diabetes. Methods: A 26-week, randomized, open-label, parallel-group, positive control drug and non-inferiority trial was conducted in 23 centers in China. A total of 563 diabetes with poor blood glucose control treated with insulin for at least 3 months before were included. The subjects were randomized(stratified block random method) into those receiving Rishulin or NovoRapid at a ratio of 3∶1. Both groups were combined with basal insulin (Lantus). The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to the end of 24 weeks of treatment. Results: For full analysis set, after 24 weeks of treatment, HbA1c level of Ruishulin group decreased from (8.66±1.28)% to (7.77±1.09)% (P<0.001), and that of NovoRapid group decreased from (8.47±1.28) % to (7.65±0.97) % (P<0.001). Treatment difference in HbA1c (NovoRapid group-Ruishulin group) was -0.061% (95%CI -0.320-0.199). HbA1c<7.0% target reacing rates were 24.26% and 21.21% (P=0.456), and HbA1c<6.5% target reacing rates were 9.65% and 6.82% (P=0.310) in Ruishulin group and NovoRapid group, repectively. The standard 2 hours postprandial blood glucose (2hPG) in Ruishulin group decreased from (16.23±5.22) mmol/L to (12.65±4.57) mmol/L (P<0.001), and 2hPG in NovoRapid group decreased from (16.13±5.37) mmol/L to (11.91)±4.21) mmol/L (P<0.001). The fingertips blood glucose at 7-point of both groups exhibited varying degrees of reduction compared with those at baseline, repectively. Positive ratios of specific antibodies were 31.68% in Ruishulin group and 36.36% in NovoRapid group (P=0.320). Ratios of negative to positive were 7.43% and 10.61% (P=0.360), and ratios of positive to negative were 10.40% and 7.58% (P=0.360) in Ruishulin group and NovoRapid group, respectively. The incidence of hypoglycemia was 60.05% and 55.40% (P=0.371), and the incidence of adverse events was 76.60% and 77.70% (P=0.818) in Ruishulin group and NovoRapid group, respectively. Conclusions: Rishulin is not inferior to NovoRapid, and has shown good efficacy and safety. It can be an ideal choice for clinicians in patients with poor blood glucose control with insulin.

Clinical and radiographic characterization of primary seminomas and nonseminomatous germ cell tumors.

BACKGROUND: Primary malignant mediastinal germ cell tumors (PMMGCTs) including seminomas and nonseminomatous germ cell tumors (NSGCTs) are rare, and sometimes the diagnosis is very difficult. PURPOSE: The purpose of this study is to compare the clinical characteristics, biomarkers, and imaging findings of seminomas and NSGCTs and to determine whether these features could help distinguish these two types of PMMGCT. MATERIAL AND METHODS: A retrospective study of 24 male patients with histopathologically proven PMMGCT was performed. We collected the information of computed tomography (CT) (the scan area ranged from the apex of lung to the costophrenic angles) and magnetic resonance imaging blood test and histology characteristics of these patients. RESULTS: Twelve of 24 cases were confirmed to be seminomas, whereas the other 12 cases were NSGCTs. Alfa-fetoprotein (AFP) was found to be elevated in all patients with NSGCT, whereas none of the patients with seminomas had elevated AFP level. Beta-human chorionic gonadotropin (ß-HCG) level was elevated in all the patients with seminomas (seven/seven), whereas in NSGCT only two of seven patients had elevated ß-HCG. Lactate dehydrogenase level was increased in five of the nine patients with seminomas, as well as in the eight patients with NSGCT. CT imaging revealed that 12 masses from the seminoma group were homogeneous, soft tissue opacity and showed minimal contrast enhancement. On the contrary, all 12 NSGCT cases showed cystic and solid masses; on contrast-enhanced CT, heterogeneous enhancement was found on the capsule of the tumor, septum, and solid masses. CONCLUSION: Seminomas and NSGCT showed different profiles of tumor biomarkers and radiographic features. Evidence from serum test, histopathological analysis, and imaging should be combined to ensure the accurate diagnosis of these two types of PMMGCT.

Real-world resource use and costs of haemophilia A-related bleeding.

INTRODUCTION: Prophylaxis treatment is recommended for haemophilia patients, but associated real-world economic costs and potential cost-savings associated with improved disease management are not fully known. This study aimed to assess haemophilia A-related resource use and cost by treatment type (prophylaxis versus non-prophylaxis) and any associated cost-savings. METHODS: Truven MarketScan Commercial claims data (2004-2012) were used to identify haemophilia A-related healthcare utilization, healthcare costs and patterns of prophylaxis and non-prophylaxis treatment among 6- to 64-year-old males. We estimated bleeding-related resource utilization and costs in three age groups (6-18, 19-44, 45-64) by treatment types and assessed the extent to which early initiation of prophylactic treatment can mitigate them. T-tests and ordinary least squares regressions were used to compare unadjusted and demographics-adjusted cost estimates. RESULTS: Among children, overall haemophilia- and bleeding-related non-pharmacy costs were substantially lower for patients receiving prophylaxis (haemophilia-related: $15,864 vs. $53,408; P < 0.001; bleeding-related: $696 vs. $2013, respectively; P = 0.04). Among younger adults (19-44), haemophilia-related non-pharmacy costs were lower for patients receiving prophylaxis ($22,028 vs. $56,311, respectively; P = 0.001). Among children, these savings fully offset the incremental pharmacy cost due to prophylaxis. Among younger adults, the savings offset approximately 34% of the incremental pharmacy cost. No differences were found for older adults (45-64). CONCLUSION: These results suggest that initiating prophylaxis earlier in life may reduce the healthcare costs of bleeding events and their long-term complications. Future studies should strive to collect more detailed information on disease severity and treatment protocols to improve estimates of disease burden.

[Meta analysis of the efficacy and safety of drainage after total hip arthroplasty].

Objective: To determine whether suction drainage is safe and effective compared with no-drainage in total hip arthroplasty. Methods: The research was based on PubMed, MEDLINE, EMBASE, Highwire, the Cochrane Library, CBM, CNKI, VIP and WFSD.The data were analysed using RevMan 5.2.Twenty-seven randomised controlled trials involving 3 603 hips were included in the analysis. Results: The meta-analysis indicate that suction drainage increases the rate of homologous blood transfusion (OR=1.98, 95%CI: 1.49-2.64, P<0.000 01)and the length of stay (OR=0.66, 95%CI: -0.01-1.33, P=0.05) (P<0.05). No significant difference was observed in the incidence of infection(OR=0.80, 95%CI: 0.52-1.22, P=0.30), wound haematomas(OR=0.47, 95%CI: 0.21-1.10, P=0.08), oozing (OR=0.93, 95%CI: 0.63-1.36, P=0.71) , deep venous thrombosis(OR=2.12, 95%CI: 0.68-6.56, P=0.19), VAS(OR=-0.06, 95%CI: -0.37-0.24, P=0.68) when the drainage group was compared with the no-drainage group. Conclusions: The comparison between suction drainage and no drainage in THA have indicated that no-drainage for easy total hip arthroplasty may be a better choice. However, orthopedic surgeon need to weigh the pros and cons of no-drainage in some complicated THAs.

Iguratimod in combination with methotrexate in active rheumatoid arthritis : Therapeutic effects.

BACKGROUND: Rheumatoid arthritis (RA) is a potentially destructive disease that may have a profound impact on patients' function and quality of life. RA therapy is still a challenge for rheumatologists; however, new antirheumatic drugs may be a treatment option for disease-modifying antirheumatic drug (DMARD)-experienced patients with active RA. OBJECTIVES: The present study is a prospective trial that aims to investigate the effects of therapy with iguratimod plus methotrexate (MTX) in comparison with iguratimod or MTX monotherapy in DMARD-experienced adult patients with active RA. METHODS: A total of 131 patients (24 men, 107 women, mean age 46.63 ± 10.61 years) with a history of being treated with traditional DMARDs were investigated. In all, 44 patients were treated with iguratimod (25 mg, twice daily, orally) plus MTX (a weekly dose of 10 mg, orally), 38 patients received iguratimod (25 mg, twice daily, orally), or 49 patients received MTX (weekly dose of 10 mg, orally) for 24 weeks. RESULTS: A therapeutic effect with iguratimod was observed between 4 and 10 weeks after treatment initiation and was effective even in patients who had a poor response to previous treatment with DMARDs. The combination of iguratimod with MTX was superior to iguratimod or MTX monotherapy. CONCLUSION: The data imply that iguratimod is a welcome addition to the small-molecule drug therapy for DMARD-experienced patients with active RA. Iguratimod (alone or in combination with MTX) is an emerging option for the treatment of DMARD-experienced adult patients with active RA who have had an inadequate response to or are intolerant of other DMARDs.

Association of tumor necrosis factor-α 308G/A polymorphism with urogenital cancer risk: a systematic review and meta-analysis.

We integrated all the eligible studies and investigated whether the TNF-α 308G/A polymorphism correlates with urogenital cancer risk. Tumor necrosis factor-α (TNF-α) is a risk factor for some urogenital cancers; however, in prostate and bladder cancers the results are controversial. PubMed, EMBASE, Web of Science, the Cochrane Library, the Chinese Biomedical Literature Database, and the Wanfang Database were searched for all case-control studies on the relationship between the TNF-α 308G/A polymorphism and susceptibility to urogenital cancer between January 1994 and January 2015. The pooled odds ratio with 95% confidence interval was calculated to assess the associations. A total of 504 articles were found, 39 of which involved 11,613 cases and 12,542 controls that fulfilled the inclusion criteria. Overall, the TNF-α 308G/A polymorphism was significantly associated with the risk of urogenital cancer. In the subgroup analysis for different cancer types, significant associations were found in cervical cancer and urothelial carcinoma, while our meta-analysis indicated that there were no significant associations between the TNF-α 308G/A polymorphism and prostate, bladder, or renal cancers. When stratified by ethnicity, significant associations were observed in Caucasian populations, whereas no significant associations were found in African-Americans, Asians, or mixed populations. Furthermore, carriers of the -308A allele among the hospital-based case-control group were at a high risk of urogenital cancer. Our meta-analysis showed that the TNF-α 308G/A polymorphism was significantly associated with urogenital cancer risk, particularly in the Caucasian and hospital-based populations.

[Progress of circulating tumor DNA methylation for gastric cancer screening and management].

Circulating tumor DNA (ctDNA) is cell-free DNA released by tumors or circulating tumor cells, containing abundant tumor-specific information that can serve as biomarkers for cancer early screening, monitoring, prognosis, and prediction of treatment response. This is particularly attractive in the field of gastric cancer, where high-quality screening, monitoring, and prediction methods are currently lacking. Gastric cancer exhibits significant tumor heterogeneity, with large differences in genetic and epigenetic characteristics among different subgroups. Methylated ctDNA has high sensitivity and specificity, which can help clarify tumor genotyping and facilitate the formulation of precise diagnostic and therapeutic strategies. Furthermore, numerous studies have confirmed the unique advantages of methylated DNA in predicting treatment response, adjuvant therapy, and drug resistance assessment, which may be used in the future to enhance the efficacy of chemotherapy regimens and improve patient chemotherapeutic response, and even treat multidrug resistance. However, there are several challenges associated with methylated ctDNA, such as low sensitivity and specificity at single-target sites, limited association between some gastric cancer subtypes and ctDNA, off-target risks, and the lack of large-scale and high-quality clinical research evidence. This review mainly summarizes current research on the methylation status of ctDNA in gastric cancer and connects these findings to early screening, recurrence monitoring, and potential treatment opportunities for gastric cancer. With advances in technology and the deepening of interdisciplinary research, ctDNA detection will reveal more disease information and become an essential foundation for gastric cancer research and precision medicine treatment.

Phylogenetic, molecular and drug-sensitivity analysis of HA and NA genes of human H3N2 influenza A viruses in Guangdong, China, 2007-2011.

Annual H3N2 subtype influenza outbreaks in Guangdong, China are a severe public health issue and require ongoing monitoring of emerging viral variants. The variation and evolution of haemagglutinin (HA) and neuraminidase (NA) genes of influenza isolates from Guangdong during 2007-2011 and others from GenBank were analysed using Lasergene 7.1 and MEGA 5.05, and serological analysis of antigens was determined by haemagglutination inhibition (HI). Susceptibility to antiviral drugs was correlated with genetic mutations. Phylogenetic analysis and alignment of HA and NA genes were performed on 18 Guangdong isolates and 26 global reference strains. The non-synonymous (dN) evolutionary rate of HA1 was 3.13 times that of HA2. Compared with the A/Perth/16/2009 vaccine HA gene, homologies of Guangdong isolates were between 98.8-99.7% and 98.0-98·4% in 2009 and 2010, respectively. Amino-acid substitutions were found in five epitopes of HA1 from Guangdong isolates between 2007 and 2011, especially in epitopes B (N160K) and D (K174R/N). The K189E/N/Q and T228A mutations in the receptor-binding site (RBS) occurred in the 2010 strains, which affected the antigenicity of HA1. The antigenicity of the epidemic H3N2 isolates in 2010 was somewhat different from that of A/Perth/16/2009. The Guangdong H3N2 isolates were determined to be oseltamivir-resistant with IC50 of 0.396 ± 0.085 nmol/l (n=17) and zanamivir-resistant with IC50 of 0.477 ± 0.149 nmol/l (n=18). Variations were present in epitopes B and D, two sites in the RBS and two glycosylation sites in the Guangdong H3N2 HA1 gene. The majority of the Guangdong H3N2 isolates were sensitive to oseltamivir and zanamivir. Compared to the World Health Organization 2012 vaccine strains, Guangdong H3N2 strains varied genetically and antigenically to some degree.

Increased hepatic yolk precursor synthesis, secretion and facilitated uptake by follicles are involved in the rejuvenation of reproductive performance of molted hens (Gallus gallus domesticus).

Molt, a natural behavior that is initiated at the end of a lay cycle in birds, is implicated in the regression of the reproductive system in birds followed by a rejuvenation of egg-laying potential. The aim of the present study was to evaluate the physiological basis for the apparent rejuvenation of egg production that occurs following molting. Eighty-three-week-old Hy-line hens, were obtained and subjected to forced molting. Blood and tissue samples were obtained at the beginning of molt (at 83 weeks of age), during molt (at 85 weeks of age) and postmolt (at 89 weeks of age). The laying performance, egg quality, blood parameters and gene expression in the liver and the ovary were investigated before, during and after molt. There was an obvious increase in the postmolt laying rate from 70% premolt to 93% postmolt. Eggshell thickness, albumin height, Haugh unit and egg shape index were all significantly improved after molt. The circulating levels of estrogen and progesterone were lower in the postmolt hens, whereas the concentrations of luteinizing hormone and follicle stimulating hormone were not significantly affected by molt. These results indicate that enhanced hepatic yolk precursor synthesis and secretion contribute to increased postmolt laying performance. Molt enhanced the sensitivity of sex hormones in F1 follicles. Augmented gene expression in the ovary was involved in the rejuvenation of the reproductive performance of molted hens. These results suggest that facilitated yolk-precursor uptake by follicles is involved in the rejuvenation of the reproductive performance of molted hens.

Protocatechuic acid, a new active substance against the challenge of avian infectious bursal disease virus.

The present study aims to investigate the potential antiviral activity of protocatechuic acid (PCA) and its mechanism against infectious bursal disease virus (IBDV) infection. In the curative test, dosages of PCA of 40, 20, and 10 mg/kg, the survival rate was 90, 90, and 60%, respectively, and the BW gain was 36.63, 31.85, and 51.8%, respectively. The survival rate for the Astragalus polysaccharide (ASP) group was significantly lower than those of the birds treated with 20 mg/kg or 40 mg/kg of PCA. The bursa indeces of chickens in 40 mg/kg, 20 mg/kg, and ASP groups were significantly higher than that of the infection group, whereas a significant increase of the spleen index was found in birds with 20 mg/kg PCA in comparison with other challenged groups. The birds treated with 20 mg/kg or 40 mg/kg of 3,4-dihydroxybenzoic acid also showed slightly higher levels of IBDV clearance in the bursa of Fabricius. Furthermore, the chickens treated with 20 mg/kg of PCA induced a significant lymphocyte proliferation and a significant increase in the CD4+/CD8+ ratio in comparison with the ASP chickens. These results imply that chickens treated with 20 mg/kg of PCA for 5 d could effectively induce active nonspecific immune responses against the IBDV infection.

Fish oil, selenium and mercury in relation to incidence of hypertension: a 20-year follow-up study.

OBJECTIVES: Long-chain omega-3 polyunsaturated fatty acids (LCω3PUFAs), selenium (Se) and mercury (Hg) are three important components in fish. The cardioprotective effect of LCω3PUFA intake has been recognized; however, the hypothesis that this benefit may be greatest with high Se and low Hg levels has not been investigated. DESIGN: A cohort of 4508 American adults aged 18-30, without hypertension at baseline in 1985, were enrolled. Six follow-ups were conducted at examinations in 1987, 1990, 1992, 1995, 2000 and 2005. Diet was assessed by a validated interviewer-administered quantitative food frequency questionnaire at exams in 1985, 1992 and 2005. Incident hypertension was defined as first occurrence at any follow-up examination of systolic blood pressure (BP) ≥ 140 mmHg, diastolic BP ≥ 90 mmHg or taking antihypertensive medication. Toenail clippings were collected in 1987, and Se and Hg levels were quantified by instrumental neutron-activation analysis. RESULT: Participants in the highest LCω3PUFA intake quartile had a significantly lower incidence of hypertension (hazard ratio: 0.65; 95% CI: 0.53-0.79; P(trend) < 0.01) compared to those in the lowest quartile after adjustment for potential confounders. Docosahexaenoic acid showed a greater inverse association than eicosapentaenoic acid. The inverse association of LCω3PUFA intake with hypertension appeared more pronounced at higher Se and lower Hg levels, although interaction tests were statistically nonsignificant. CONCLUSIONS: Our findings indicated that LCω3PUFA intake was inversely associated with incidence of hypertension. The prior hypothesis that the potential antihypertensive effect of LCω3PUFA intake varies depending on joint levels of Se and Hg received modest support and cannot be ruled out.

[The efficacy and safety of daratumumab in relapsed and refractory multiple myeloma].

Objective: To investigate the efficacy and safety of daratumumab in relapsed and refractory multiple myeloma (RRMM) . Methods: The clinical characteristics, adverse reactions, efficacy, and prognosis of 46 patients with RRMM treated with daratumumab in Shanghai Changzheng Hospital from September 2017 to March 2020 were retrospectively analyzed. Results: All patients were treated with daratumumab-based regimen: 8 in the Dd group, 35 in the DRd group, and 3 in the DVd group. With a median follow-up of 9.6 months, the overall response rate (ORR) was 75% [complete remission (CR) rate 18.2% ] among the 44 patients available for evaluation. The ORRs of patients resistant to bortezomib, lenalidomide, and both were 70.6% , 69.2% , and 63.6% , respectively. The CR rates of patients resistant to bortezomib, lenalidomide, and both were 17.6% , 11.5% , and 13.6% , respectively. No significant difference was observed in ORR and CR rates among the three groups. The ORRs of the DRd, DVd, and Dd groups were 85.3% , 66.7% , and 28.6% , respectively (P=0.007) . The median PFS of 46 patients was 8.9 months, the median OS was not reached, and the 1-year OS rate was 74% . The median PFS and OS in the DRd group were longer than those in the Dd group (PFS: 14.4 months vs 2.0 months; OS: not reached vs 5.2 months) . After treatment with daratumumab, neutropenia is the most common hematological adverse reaction above grade 3. Non-hematological adverse reactions are mainly infusion-related adverse reactions and infections. Prognostic analysis showed that patients with extramedullary invasion had shorter PFS and OS compard with patients without extramedullary invasion (PFS: 5.7 vs 14.4 months, P=0.033; OS: 6.3 months vs not reached, P=0.029) . The OS of patients with an ECOG score of 3-4 was significantly shorter than patients with an ECOG score of 1-2 (5.9 months vs not reached, P=0.004) . Conclusion: Daratumumab-based regimens have good efficacy and safety in the treatment of RRMM.

Development, verification, and comparison of a risk stratification model integrating residual cancer burden to predict individual prognosis in early-stage breast cancer treated with neoadjuvant therapy.

BACKGROUND: A favorable model for predicting disease-free survival (DFS) and stratifying prognostic risk in breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) is lacking. The aim of the current study was to formulate an excellent model specially for predicting prognosis in these patients. PATIENTS AND METHODS: Between January 2012 and December 2015, 749 early-stage BC patients who received NAC in Xijing hospital were included. Patients were randomly assigned to a training cohort (n = 563) and an independent cohort (n = 186). A prognostic model was created and subsequently validated. Predictive performance and discrimination were further measured and compared with other models. RESULTS: Clinical American Joint Committee on Cancer stage, grade, estrogen receptor expression, human epidermal growth factor receptor 2 (HER2) status and treatment, Ki-67 expression, lymphovascular invasion, and residual cancer burden were identified as independent prognostic variables for BC treated with NAC. The C-index of the model consistently outperformed other available models as well as single independent factors with 0.78, 0.80, 0.75, 0.82, and 0.77 in the training cohort, independent cohort, luminal BC, HER2-positive BC, and triple-negative BC, respectively. With the optimal cut-off values (280 and 360) selected by X-tile, patients were categorized as low-risk (total points ≤280), moderate-risk (280 < total points ≤ 360), and high-risk (total points >360) groups presenting significantly different 5-year DFS of 89.9%, 56.9%, and 27.7%, respectively. CONCLUSIONS: In patients with BC, the first model including residual cancer burden index was demonstrated to predict the survival of individuals with favorable performance and discrimination. Furthermore, the risk stratification generated by it could determine the risk level of recurrence in whole early-stage BC cohort and subtype-specific cohorts, help tailor personalized intensive treatment, and select comparable study cohort in clinical trials.

Growth rate of human fingernails and toenails in healthy American young adults.

BACKGROUND: Human nail clippings are increasingly used in epidemiological studies as biomarkers for assessing diet and environmental exposure to trace elements or other chemical compounds. However, little is known about the growth rate of human nails. OBJECTIVE: To estimate the average growth rate of fingernails and toenails and examine factors that may influence nail growth rate. METHODS: Twenty-two healthy American young adults marked their nails close to the proximal nail fold with a provided nail file following a standardized protocol, and recorded the date and the distance from the proximal nail fold to the mark. One to three months later, participants recorded the date and distance from the proximal nail fold to the mark again. Nail growth rate was calculated based on recorded distance and time between the two measurements. RESULTS: Average fingernail growth rate was faster than that of toenails (3.47 vs. 1.62 mm/month, P < 0.01). There was no significant difference between right and left fingernail/toenail growth rates. The little fingernail grew slower than other fingernails (P < 0.01); the great toenail grew faster than other toenails (P < 0.01). Younger age, male gender, and onychophagia were associated with faster nail growth rate; however, the differences were not statistically significant. CONCLUSION: Nail growth rates have increased compared with previous estimates conducted decades ago. Toenail clippings may reflect a long exposure time frame given the relatively slow growth rate.

Hepatitis B virus protein preS2 potentially promotes HCC development via its transcriptional activation of hTERT.

BACKGROUNDS AND AIMS: Telomerase is significantly reactivated in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Our previous studies showed that the transactivation unit of HBV surface (S) gene, preS2, could upregulate human telomerase reverse transcriptase (hTERT) expression and telomerase activity of HepG2 cells. Here, we aim to explore the functions, and the underlying mechanisms, of this preS2-mediated hTERT upregulation during HCC development. METHODS: An antisense blocking assay was performed on HBV-integrated HepG2.2.15 cells. The expression of hTERT was examined in clinical samples to test the role of the preS2-mediated hTERT upregulation in HCC development in vivo. In order to explore the mechanisms of preS2-mediated hTERT upregulation, co-transfection, reporter assays and electrophoretic mobility shift assays (EMSA) were performed. RESULTS: Blocking preS2 expression reduced hTERT expression, telomerase activity, cell proliferation and tumorigenicity of HepG2.2.15. A region located between -349 and -329 bp upstream of the transcription initiation site of hTERT was identified as responsible for the preS2-mediated effect. preS2 interacted with the preS2-responsible region (PRR) and activated the hTERT promoter. Importantly, hTERT was also highly expressed in preS2-positive human HCC samples. All these findings strongly suggest that preS2 may promote HCC development via hTERT activation. CONCLUSIONS: HBV protein preS2 upregulates hTERT via the PRR element in promoting HCC development.