Construct a Magnetic Pt/Ru Alloy Peroxidase Mimic As a Reusable and Cost-Effective "Signal-Off" Sensing Platform for Sensitive and Wide-Linear-Range Assay.

"Signal-off" nanozyme sensing platforms are usually employed to detect analytes (e.g., ascorbic acid (AA) and alkaline phosphatase (ALP)), which are mostly based on oxidase (OXD) nanozymes. However, their drawbacks, like dissolved oxygen-dependent catalysis capability, relatively low enzyme activity, limited amount, and kind, may not favor sensing platforms' optimization. Meanwhile, with the need for sustainable development, a reusable "signal-off" sensing platform is essential for cutting down the cost of the assay, but it is rarely developed in previous studies. Magnetic peroxidase (POD) nanozymes potentially make up the deficiencies and become reusable and better "signal-off" sensing platforms. As a proof of concept, we first construct Fe3O4@polydopamine-supported Pt/Ru alloy nanoparticles (IOP@Pt/Ru) without stabilizers. IOP@Pt/Ru shows high POD activity with Vmax of 83.24 × 10-8 M·s-1 for 3,3',5,5'-Tetramethylbenzidine (TMB) oxidation. Meanwhile, its oxidation rate for TMB is slower than the reduction of oxidized TMB by reducers, favorable for a more significant detection signal. On the other hand, IOP@Pt/Ru possesses great magnet-responsive capability, making itself be recycled and reused for at least 15-round catalysis. When applying IOP@Pt/Ru for AA (ALP) detection, it performs better detectable adaptability, with a linear range of 0.01-0.2 mM (0.1-100 U/L) and a limit of detection of 0.01 mM (0.05 U/L), superior to most of OXD nanozyme-based ALP sensing platform. Finally, IOP@Pt/Ru's reusable assay was demonstrated in real blood samples for ALP assay, which has never been explored in previous studies. Overall, this study develops a reusable "signal-off" nanozyme sensing platform with superior assay capabilities than traditional OXD nanozymes, paves a new way to optimize nanozyme-based "signal-off" sensing platforms, and provides an idea for constructing inexpensive and sustainable sensing platforms.

Effects of Talaromyces marneffei on Complete Blood Count by a Sysmex XN-9000 Analyzer.

BACKGROUND: Talaromyces marneffei (T. marneffei) infection detected in the peripheral blood smears has been described by several reports. We studied the effects of T. marneffei in peripheral blood samples on complete blood count (CBC) using a Sysmex XN-9000 analyzer. METHODS: In a simulated T. marneffei infection model, blood samples with and without infectious diseases were selected, with high, medium, and low levels of white blood cell (WBC) and platelet (PLT) count, respectively. All samples were detected immediately and after a warm bath of 37℃ for 2 hours. RESULTS: WBC count of all samples was significantly increased by T. marneffei from a certain concentration and higher. For all samples, the effect of T. marneffei on WBC count after warm bath was significantly reduced compared to that on immediate WBC count from 4 - 6 x 109/L T. Marneffei and higher (p < 0.05). The presence of T. marneffei in all blood samples did not affect the results of PLT count. For all samples, the obvious effects of T. marneffei on WBC differential (WDF) and white cell nucleated red blood cell (WNR) scatter plots were from 4 - 6 x 109 T Marneffei and higher. CONCLUSIONS: As a kind of intracellular yeast, T. marneffei may affect WBC count, NRBC count, and WBC differential count of peripheral blood samples when the yeast concentration is (4 - 6) x 109 T Marneffei and higher. Moreover, the unique scatter plot cloud on WDF and WNR scatter plots caused by T. marneffei, may become an important clue pointing toward T. marneffei in peripheral blood.

Non-structural proteins of bovine viral diarrhea virus.

Bovine viral diarrhea virus (BVDV) belongs to the family Flaviviridae genus pestivirus. The viral genome is a single-stranded, positive-sense RNA that encodes four structural proteins (i.e., C, Erns, E1, and E2) and eight non-structural proteins (NSPs) (i.e., Npro, p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B). Cattle infected with BVDV exhibit a number of different clinical signs including diarrhea, abortion, and other reproductive disorders which have a serious impact on the cattle industry worldwide. Research on BVDV mainly focuses on its structural protein, however, progress in understanding the functions of the NSPs of BVDV has also been made in recent decades. The knowledge gained on the BVDV non-structural proteins is helpful to more fully understand the viral replication process and the molecular mechanism of viral persistent infection. This review focuses on the functions of BVDV NSPs and provides references for the identification of BVDV, the diagnosis and prevention of Bovine viral diarrhea mucosal disease (BVD-MD), and the development of vaccines.

Quantitative Analysis of Polysaccharide Composition in Polyporus umbellatus by HPLC-ESI-TOF-MS.

Polyporus umbellatus is a well-known and important medicinal fungus in Asia. Its polysaccharides possess interesting bioactivities such as antitumor, antioxidant, hepatoprotective and immunomodulatory effects. A qualitative and quantitative method has been established for the analysis of 12 monosaccharides comprising polysaccharides of Polyporus umbellatus based on high-performance liquid chromatography coupled with electrospray ionization-ion trap-time of flight-mass spectrometry. The hydrolysis conditions of the polysaccharides were optimized by orthogonal design. The results of optimized hydrolysis were as follows: neutral sugars and uronic acids 4 mol/L trifluoroacetic acid (TFA), 6 h, 120 °C; and amino sugars 3 mol/L TFA, 3 h, 100 °C. The resulting monosaccharides derivatized with 1-phenyl-3-methyl-5-pyrazolone have been well separated and analyzed by the established method. Identification of the monosaccharides was carried out by analyzing the mass spectral behaviors and chromatography characteristics of 1-phenyl-3-methyl-5-pyrazolone labeled monosaccharides. The results showed that polysaccharides in Polyporus umbellatus were composed of mannose, glucosamine, rhamnose, ribose, lyxose, erythrose, glucuronic acid, galacturonic acid, glucose, galactose, xylose, and fucose. Quantitative recoveries of these monosaccharides in the samples were in the range of 96.10-103.70%. This method is simple, accurate, and sensitive for the identification and quantification of monosaccharides, and can be applied to the quality control of Polyporusumbellatus as a natural medicine.

Prognostic significance of Ki67 in Chinese women diagnosed with ER+/HER2- breast cancers by the 2015 St. Gallen consensus classification.

BACKGROUND: This study evaluated the distribution pattern of the Ki67-labeling index (LI) among patients at a Chinese breast cancer center, and analyzed its prognostic significance in the 2015 St Gallen consensus breast cancer classification, estrogen receptor-positive and human epidermal growth factor receptor 2-negative(ER+/HER2-)subtype. METHODS: We classified 939 women with ER+/HER2- breast cancer into three groups by Ki67-LI levels, and followed their clinicopathologic characteristics and prognoses. RESULTS: In the 939 eligible subjects, 342 had Ki67-LI ≤10% (Ki67Low), 281 had Ki67-LI between 10 and 30% (Ki67Medium), and 316 had Ki67-LI ≥30% (Ki67High). Although the Ki67High group had less favorable clinicopathologic factors, the Ki67Medium group's factors varied considerably. Kaplan-Meier estimates showed that disease-free survival(DFS) for the Ki67Medium group was significantly shorter than the Ki67Low group but longer than the Ki67High group. Ki67-LI had independent prognostic significance in multivariate analysis. Other diagnostic factors, including tumor size >2 cm, positive lymph nodes, and grade III disease, were significantly associated with poorer disease-free survival only in the Ki67Medium group. CONCLUSIONS: For patients with ER+/HER2- breast cancer, we confirmed three distinct risk patterns by Ki67-LI levels according to the 2015 St Gallen consensus. For patients with clearly low or high Ki67-LI, straightforward clinical decisions could be offered, but for patients with intermediate Ki67-LI, other factors might provide valuable information.

Prospective comparison of Sapylin and Avitene for reducing hydrops after axillary lymphadenectomy in breast cancer patients.

BACKGROUND: This study compared the efficacy of Sapylin and Avitene in reducing postoperative axillary seroma formation and effusion when applied topically after axillary lymphadenectomy. METHODS: A total of 224 patients were randomly divided into a Sapylin treatment group (STG), an Avitene treatment group, and a control group (CG). All patients underwent axillary lymphadenectomy and were treated during surgery with Sapylin, Avitene, or neither according to their group assignment. The duration and amount of postoperative drainage, as well as the occurrence of seromas were recorded. Outcomes were compared by one-way analysis of variance and chi-square tests. RESULTS: Baseline patient data, including age, body mass index, history of neoadjuvant chemotherapy, type of surgery, number of resected lymph nodes, and number of positive metastases did not differ among the three groups. Patients in both the STG and the Avitene treatment group experienced significantly fewer days of drainage than those in the CG; there was no significant difference in drainage tube retention time between the two treated groups. The STG experienced significantly less drainage volume than the CG. Fewer patients in both treatment groups required seroma treatment or experienced complications compared with CG patients. CONCLUSIONS: Both Sapylin and Avitene effectively reduced postoperative subcutaneous fluid accumulation after axillary lymphadenectomy. These treatments may be particularly useful for breast cancer patients at high risk of seroma formation, especially those with hypertension, diabetes mellitus, or a high body mass index who undergo axillary lymphadenectomy.

Comparison of the Therapeutic Efficacy of the Early and the Delayed Use of Vinorelbine-Based Regimens for Patients with Advanced Breast Cancer.

BACKGROUND: The aim of this study was to evaluate the efficacy of vinorelbine-based regimens as first-, second- and more-line therapies in advanced breast cancer (ABC) and to analyze the best timing of vinorelbine treatment. METHODS: A total of 71 ABC patients were retrospectively reviewed. Of these, 35 patients were treated with vinorelbine-based regimens as first-line chemotherapy, and 36 patients were treated with vinorelbine-based regimens as second-line or more-line therapy. The primary end point of the study was progression-free survival (PFS). RESULTS: No difference was found in baseline characteristics between the two groups (p > 0.1 for all comparisons). There was a significant difference in the objective response rate (ORR; p = 0.006) and clinical benefit rate (CBR; p = 0.013) between the first-line group and the second- or more-line groups. In the vinorelbine first-line group, the ORR was 68.6% (24 patients), and in the second-line or more-line groups the ORR was 36.1% (13 patients). A significant difference in PFS between the first-line group and the second-line or more-line groups was also observed (p = 0.030). The median PFS in the overall population was 6.3 ± 1.32 months (95% CI 3.69-8.90). The median PFS was 11.1 ± 3.76 months (95% CI 3.73-18.47) in the first-line group compared with 5.2 ± 1.35 months (95% CI 2.54-7.85) in the second-line or more-line groups. In patients treated with vinorelbine-trastuzumab combination as the first-line therapy, a complete response was observed in 1 patient (12.5%) and partial response in 5 patients (62.5%), giving an ORR of 75.0%. Progressive disease was observed in 1 patient (12.5%), and stable disease in 1 patient (12.5%), leading to a CBR of 87.5%. The median PFS was 13.8 ± 2.75 months (95% CI 8.42-19.18), and median OS was 37.0 ± 11.6 months (95% CI 14.18-59.82). No significant difference was found in overall survival (OS) between the groups (p = 0.612). CONCLUSION: For ABC patients, no significant difference in median OS was found between the early use and delayed use of vinorelbine-based regimens, but the short-term efficacy and PFS of vinorelbine-based regimens were significantly better in the early use group than in the delayed use group.

What lies behind chemotherapy-induced amenorrhea for breast cancer patients: a meta-analysis.

To evaluate the incidence of chemotherapy-induced amenorrhea (CIA) and its therapeutic impact in premenopausal breast cancer patients. A systematic search was performed to identify clinical studies that compared the incidence of CIA with different chemotherapy regimens and oncological outcomes with and without CIA. The fixed-effects and random-effects models were used to assess the pooled estimates. Heterogeneity and sensitivity analyses were performed to explore heterogeneity among studies and to assess the effects of study quality. A total of 15,916 premenopausal breast cancer patients from 46 studies were included. The cyclophosphamide-based regimens, taxane-based regimens, and anthracycline/epirubicin-based regimens all increased the incidence of CIA with pooled odds ratios of 2.25 (95 % CI 1.26-4.03, P = 0.006), 1.26 (95 % CI 1.11-1.43, P = 0.0003) and 1.39 (95 % CI 1.15-1.70, P = 0.0008), respectively. The three-drug combination regimens of cyclophosphamide,anthracycline/epirubicin, and taxanes (CAT/CET) caused the highest rate of CIA compared with the other three drug combinations (OR 1.41, 95 % CI 1.16-1.73, P = 0.0008). Tamoxifen therapy was also correlated with a higher incidence of CIA, with an OR of 1.48. Patients with CIA were found to exhibit better disease-free survival (DFS) and overall survival (OS) compared with patients without CIA. With respect to molecular subtype, this DFS advantage remained significant in hormone-sensitive patients (HR 0.61, 95 % CI 0.52-0.72, P < 0.00001). The current meta-analysis has demonstrated that anthracycline/epirubicin, taxanes, cyclophosphamide, and tamoxifen all contributed to elevated rates of CIA, and CIA was not merely a side effect of chemotherapy but was a better prognostic marker, particularly for ER-positive premenopausal early-stage breast cancer patients. However, this topic merits further randomized control studies to detect the associations between CIA and patient prognosis after adjusting for age, ER status, and other influential factors.

HER-2 positive breast cancer is associated with an increased risk of positive cavity margins after initial lumpectomy.

BACKGROUND: The effect of breast cancer subtype on margin status after lumpectomy remains unclear. This study aims to determine whether approximated breast cancer subtype is associated with positive margins after lumpectomy, which could be used to determine if there is an increased risk of developing local recurrence (LR) following breast-conserving surgery. METHODS: We studied 1,032 consecutive patients with invasive cancer who received lumpectomies and cavity margin (CM) assessments from January 2003 to November 2012. The following data were collected: patient age, cT stage, pT stage, grade, status of CM, lymph node status, menopausal status, ER, PR, HER-2, and Ki67, as well as the presence of extensive intraductal component (EIC) and lymphovascular invasion (LVI). A χ2 test was used to compare categorical baseline characteristics. Univariate and multivariate logistic regression analyses were performed to evaluate associations between pathologic features of CM status. Kaplan-Meier actuarial cumulative rates of LR (ipsilateral in-breast) were calculated. RESULTS: A total of 7,884 pieces of marginal tissue were collected from 1,032 patients, and 209 patients had positive CMs. Of the patients tested, 52.3% had luminal A subtype, 14.9% were luminal B, 12.8% were luminal-HER-2, 8.1% were HER-2 enriched, and 11.8% were triple negative. Univariate analysis showed that EIC (P < 0.001), LVI (P = 0.026), pN stage (N1 vs. N0: P = 0.018; N3 vs. N0: P < 0.001), and luminal B (P = 0.001) and HER-2 (P < 0.001) subtypes were associated with positive CMs. Multivariable analysis indicated that only EIC (P < 0.001), pN stage (P = 0.003), and HER-2 subtype (P < 0.001) were significantly correlated with positive CMs. On multivariable analysis, HER-2 subtype was an independent prognostic factor in LR (P = 0.031). CONCLUSIONS: The HER-2 subtype was the predictive factor most associated with positive CMs and an independent prognostic factor for LR. This result suggests that the increased risk of LR in HER-2 breast cancer is due to an increased microscopic invasive tumor burden, which is indicated by margin status after lumpectomy.

Which nomogram is best for predicting non-sentinel lymph node metastasis in breast cancer patients? A meta-analysis.

To present a systematic [corrected] review and meta-analysis to evaluate the nomograms developed to predict non-sentinel lymph node (NSLN) metastasis in breast cancer patients. We focused on the six nomograms (Cambridge, MSKCC, Mayo, MDA, Tenon, and Stanford) that are the most widely validated. The AUCs were converted to odds ratios for the meta-analysis. In total, the Cambridge, Mayo, MDA, MSKCC, Stanford, and Tenon models were validated in 2,156, 2,431, 843, 8,143, 3,700, and 3,648 patients, respectively. The pooled AUCs for the Cambridge, MDA, MSKCC, Mayo, Tenon, and Stanford models were 0.721, 0.706, 0.715, 0.728, 0.720, and 0.688, respectively. Subgroup analysis revealed that in populations with a higher micrometastasis rate in the SLNs, the Tenon and Stanford models had a significantly higher predictive accuracy. A meta-regression analysis revealed that the SLN micrometastasis rate, but not the NSLN-positivity rate, was associated with improved predictive accuracy in the Tenon and Stanford models. The performance of the MSKCC and Cambridge models was not influenced by these two factors. All of these prediction models perform better than random chance. The Stanford model seems to be relatively inferior to the other models. The accuracy of the Tenon and Stanford models is influenced by the tumor burden in the SLNs.

Axillary web syndrome following secondary breast-conserving surgery: a case report.

BACKGROUND: Axillary web syndrome is a cause of significant morbidity in the early postoperative period after axillary surgery. CASE PRESENTATION: A patient developed axillary web syndrome after secondary breast surgery and recovered in 3 weeks through physical therapy and using Aescuven Forte. DISCUSSION: The pathogenesis of axillary web syndrome is not clear. It is reported that axillary surgery is the main cause. The presented case indicates that tissue injury might be an important cause of axillary web syndrome. Though axillary web syndrome is self-limiting, special physical therapy and Aescuven Forte can shorten the natural duration. CONCLUSION: Secondary breast surgery could cause axillary web syndrome. Physical therapy and Aescuven Forte could shorten the duration of the self-limited morbidity.

Validation and comparison of models to predict non-sentinel lymph node metastasis in breast cancer patients.

Several models for predicting the risk of non-sentinel lymph node (NSLN) metastasis in breast cancer patients with positive sentinel lymph nodes (SLNs) have been developed. The purpose of this study was to validate and compare these models in Chinese patients. A total of 159 breast cancer patients with positive SLNs treated at our institution were included. Among them, 81 (50.9%) patients had at least one NSLN involvement. The Cambridge, Mou, Mayo, Tenon, MDA, Memorial Sloan-Kettering Cancer Center (MSKCC), Ljubljana, SNUH, Turkish, Louisville, Stanford, and Saidi models were evaluated and compared using receiver operating characteristic (ROC) curves, calibration plots, and false negative (FN) rates. The Cambridge and Mou models outperformed the others, both with area under the ROC curves (AUCs) of 0.73. The Mayo, Tenon, MDA, MSKCC, Turkish, Ljubljana, SNUH, and Louisville models had AUCs of 0.68, 0.66, 0.66, 0.64, 0.63, 0.62, 0.61, and 0.60, respectively. The Stanford and Saidi models did not present any discriminative capabilities, with AUCs of 0.54 and 0.50, respectively. The Cambridge, MSKCC, and Mayo models were well calibrated. With adjusted thresholds, the Mayo model outperformed the others by classifying the highest proportion of patients (20%) into the low-risk group. Our study revealed that the Cambridge and Mou models performed well in Chinese patients. The ROC curves, calibration plots, and FN rates should be used together for the accurate evaluation of prediction models. Selection of these models should be based on the clinicopathological features of the targeted population. The models specifically designed for patients with micrometastases or macrometastases of SLNs are needed in the future.

Clinical outcomes of breast-conserving surgery in patients using a modified method for cavity margin assessment.

BACKGROUND: This study describes a modified intraoperative method for cavity margin (CM) assessment in place of lumpectomy margin assessment in patients undergoing breast-conserving surgery (BCS). METHODS: This is a retrospective review of 422 breast cancer patients undergoing BCS with intraoperative CM assessment. After an initial lumpectomy with intent to obtain ≥1-cm margins, separate specimens 1 × 1 cm, 0.5-cm thick were taken from the cavity margin circumferentially. These were frozen without reference to the side of the new margin as a time-saving measure, and parallel sections of the resected surface were evaluated. RESULTS: After a median follow-up of 55.5 months, a cumulative 5-year locoregional recurrence-free survival rate of 95.3%, metastasis-free survival rate of 97.8%, disease-free survival rate of 88.3%, and overall survival rate of 96.0%, was achieved. The CM positivity rates were of no statistical difference when <7, 7-8, and >8 CMs were assessed. The second operation rate was 3.5% because of the false-negative results of the frozen section analysis on CMs. Univariate and multivariate analysis revealed that a higher pN stage and cT stage as well as a lack of adjuvant chemotherapy or radiation demonstrated significantly worse clinical outcomes. Locoregional recurrences and metastasis are both correlated with worse overall survival. The number of the CMs assessed was not associated with clinical outcomes. CONCLUSIONS: The modified CM assessment presented here is a rapid, accurate, and oncologically safe approach for margin evaluation in BCS patients. Lumpectomy margin assessment might be spared when this method is used.

A comparison of survival outcomes and side effects of toremifene or tamoxifen therapy in premenopausal estrogen and progesterone receptor positive breast cancer patients: a retrospective cohort study.

BACKGROUND: In premenopausal women, endocrine adjuvant therapy for breast cancer primarily consists of tamoxifen alone or with ovarian suppressive strategies. Toremifene is a chlorinated derivative of tamoxifen, but with a superior risk-benefit profile. In this retrospective study, we sought to establish the role of toremifene as an endocrine therapy for premenopausal patients with estrogen and/or progesterone receptor positive breast cancer besides tamoxifen. METHODS: Patients with early invasive breast cancer were selected from the breast tumor registries at the Sun Yat-Sen Memorial Hospital (China). Premenopausal patients with endocrine responsive breast cancer who underwent standard therapy and adjuvant therapy with toremifene or tamoxifen were considered eligible. Patients with breast sarcoma, carcinosarcoma, concurrent contralateral primary breast cancer, or with distant metastases at diagnosis, or those who had not undergone surgery and endocrine therapy were ineligible. Overall survival and recurrence-free survival were the primary outcomes measured. Toxicity data was also collected and compared between the two groups. RESULTS: Of the 810 patients reviewed, 452 patients were analyzed in the study: 240 received tamoxifen and 212 received toremifene. The median and mean follow up times were 50.8 and 57.3 months, respectively. Toremifene and tamoxifen yielded similar overall survival values, with 5-year overall survival rates of 100% and 98.4%, respectively (p = 0.087). However, recurrence-free survival was significantly better in the toremifene group than in the tamoxifen group (p = 0.022). Multivariate analysis showed that recurrence-free survival improved independently with toremifene (HR = 0.385, 95% CI = 0.154-0.961; p = 0.041). Toxicity was similar in the two treatment groups with no women experiencing severe complications, other than hot flashes, which was more frequent in the toremifene patients (p = 0.049). No patients developed endometrial cancer. CONCLUSION: Toremifene may be a valid and safe alternative to tamoxifen in premenopausal women with endocrine-responsive breast cancer.

Cavity margins and lumpectomy margins for pathological assessment: which is superior in breast-conserving surgery?

PURPOSE: This prospective cohort study aimed to compare the efficacy of cavity margins (CMs) and lumpectomy margins (LMs) for pathological assessment in breast-conserving surgery. METHODS: We assessed the CMs and LMs of 163 breast cancer patients during breast-conserving surgery. We compared and analyzed the positivity rates of CM and LM. RESULTS: The positivity rate of CM at the case level and individual margin level was 30.7% and 8.0%, respectively. The positivity rate of LM was 12.3%, 33.1%, and 45.4% at the case level and 1.8%, 6.2%, and 9.1% at the individual margin level, when we used the National Surgical Adjuvant Breast and Bowel Project criteria (ink-free), 1 mm-free criteria and 2 mm-free criteria, respectively. The positivity rate of LM with 1 mm-free criteria was similar to that of CM. Delivery of neoadjuvant chemotherapy increased the positivity rate of CM (50.0% versus 25.2%; P < 0.01) but not LM (41.6% versus 30.7%; P > 0.05) at the case level, whereas the positivity rate of CM and LM both increased after neoadjuvant chemotherapy at the margin level (CMs: 15.5% versus 5.6%, P < 0.001; and LMs: 10.7% versus 4.9%, P < 0.001). In univariate and multivariate analysis, delivery of neoadjuvant chemotherapy, higher node-positive stage, and presence of ductal carcinoma in situ component were correlated with positive CM, whereas positive human epidermal growth factor receptor 2 status and higher node-positive stage were associated with positive LM. CONCLUSIONS: Ink-free criteria may be insufficient for LM assessment in breast-conserving surgery, and at least 1 mm width LM is suggested. After the delivery of neoadjuvant chemotherapy, CM assessment should be routinely performed in addition to LM assessment.

Recent Progress on Tick-Borne Animal Diseases of Veterinary and Public Health Significance in China.

Ticks and tick-borne diseases pose a growing threat to human and animal health, which has brought great losses to livestock production. With the continuous expansion of human activities and the development of natural resources, there are more and more opportunities for humans to contract ticks and tick-borne pathogens. Therefore, research on ticks and tick-borne diseases is of great significance. This paper reviews recent progress on tick-borne bacterial diseases, viral diseases, and parasitic diseases in China, which provides a theoretical foundation for the research of tick-borne diseases.

An on-line detection system for screening small molecule inhibitors of α-Amylase and α-Glucosidase in Prunus mume.

High-throughput screening of inhibitors from natural products is an efficient approach to target key enzymes in diabetes progression. In this study, an on-line detection system was established for the first time to rapidly screen inhibitors of α-amylase and α-glucosidase from Prunus mume. Among 28 identified compounds, 26 and 21 compounds showed strong inhibitory effect against α-amylase and α-glucosidase, respectively. Their inhibitory effects were validated by in vitro enzyme assay and fluorescence quenching which demonstrated that these inhibitors effectively interfered enzyme active sites. The inhibition kinetics suggested that chemical structures are of great importance for interfering the enzyme structures and their microenvironment polarity. Among evaluated compounds, isorhamnetin-3-O-glucoside (19) showed the strongest binding activities to α-amylase and α-glucosidase (6.34×106·nmol-1 and 6.28×106·nmol-1, respectively) by the on-line detection system. Its IC50 values were 0.16 ± 0.06 and 0.09 ± 0.01 µM against α-amylase and α-glucosidase, respectively. 19 gave a much higher Ki for α-amylase (0.1307 mM) than α-glucosidase (0.0063 mM), indicating its selectivity towards α-glucosidase. This reported method was rapid and reliable to identify prototype inhibitors against key enzymes in diabetes, and thus might serve as a general platform to screen enzyme inhibitors from natural products.

[Research progress of c-di-GMP in the regulation of Escherichia coli biofilm].

Escherichia coli biofilm is a complex membrane aggregation produced by the adhesion and secretion of extracellular polymeric substances by E. coli cells aggregated on specific media. Pathogenic E. coli will evade the immune system and the impact of various harmful factors in the environment after the formation of biofilm, causing sustained and even fatal damage to the host. Cyclic diguanosine monophosphate (c-di-GMP) is a second messenger ubiquitous in bacteria and plays a crucial role in regulating biofilm formation. This paper reviewed the recent studies about the role of c-di-GMP in the movement, adhesion, and EPS production mechanism of E. coli during biofilm formation, aiming to provide a basis for inhibiting E. coli biofilm from the perspective of c-di-GMP.

Multicenter phase II trial of Camrelizumab combined with Apatinib and Eribulin in heavily pretreated patients with advanced triple-negative breast cancer.

In the later-line setting or for patients with PD-L1-negative tumors, immunotherapy-based regimens remain ineffective against advanced triple-negative breast cancer (TNBC). In this multicentered phase II trial (NCT04303741), 46 patients with pretreated advanced TNBC were enrolled to receive camrelizumab 200 mg (day 1), and apatinib 250 mg daily, plus eribulin 1.4 mg/m2 (day 1 and 8) on a 21-day cycle until progression, or unacceptable toxicity. Primary endpoint was objective response rate (ORR) according to RECIST 1.1. Secondary endpoints included toxicities, disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), and 1-year overall survival. With a median of 3 lines of prior chemotherapy in the advanced setting, 17.4% had received PD-1/PD-L1 blockade plus chemotherapy for advanced disease. The ORR was 37.0% (17/46, 95% CI 23.2-52.5). The DCR was 87.0% (40/46, 95% CI 73.7-95.1). Median PFS was 8.1 (95% CI 4.6-10.3) months. Tertiary lymphoid structure was associated with higher ORR. Patients with lower tumor PML or PLOD3 expression had favorable ORR and PFS. PD-L1 status was not associated with ORR/PFS. Grade 3/4 treatment-related adverse events occurred in 19 (41.3%) of 46 patients. Camrelizumab plus apatinib and eribulin shows promising efficacy with a measurable safety profile in patients with heavily pretreated advanced TNBC.

A single-center, prospective and randomized controlled study: Can the prophylactic use of lamivudine prevent hepatitis B virus reactivation in hepatitis B s-antigen seropositive breast cancer patients during chemotherapy?

Over the past four decades, chemotherapy has played an important role in prolonging survival in breast cancer patients. However, it may also result in undesirable side effects such as hepatitis B virus (HBV) reactivation seen in this study. With the increasing use of chemotherapy paralleling the rise in breast cancer incidence, the occurrence of HBV reactivation is likely to further increase. Several strategies use lamivudine to deal with this problem. Initially, lamivudine had been used to treat patients who developed alanine transaminase elevation attributable to HBV reactivation during chemotherapy. However, using this strategy, fatal reactivation has also been reported. Later studies have suggested that prophylactic lamivudine significantly reduces HBV reactivation and its associated morbidity. However, these studies were based mainly on patients with lymphoma, whereas studies on breast cancer patients were few. Moreover, these studies were retrospective. Recently, a prospective study has recommended that deferred preemptive lamivudine could be a comparable alternative to the prophylactic strategy. However, it was not a randomized controlled study. In this study, it was examined the efficacy of the prophylactic strategy in hepatitis B s-antigen seropositive breast cancer patients during chemotherapy using a prospective, randomized controlled study. Two groups were studied. One group consisted of 21 patients who were treated with prophylactic lamivudine, the other group consisted of 21 patients who were not treated with prophylactic lamivudine. The results showed that the prophylactic lamivudine strategy significantly decreased the incidence of HBV reactivation (0 vs. 28.6%, P = 0.021). It was conclude that the prophylactic lamivudine strategy significantly reduces the incidence of HBV reactivation for hepatitis B s-antigen seropositive breast cancer undergoing chemotherapy.