Relationship between social support and self-care ability among patients with breast cancer during rehabilitation: The multiple mediating roles of resilience and depression.

AIMS: To identify the multiple mediating effects of resilience and depression between social support and self-care ability among patients with breast cancer during rehabilitation to provide reference for developing and implementing targeted interventions. DESIGN: A cross-sectional study reported according to the STROBE checklist. METHODS: A convenience sample of 320 patients with breast cancer during rehabilitation was recruited from one hospital in China. Data were collected from April to August 2022 using a self-report questionnaire, including the demographic and clinical information, Appraisal of Self-Care Agency Scale-Revised, Multidimensional Scale of Perceived Social Support, Connor-Davidson Resilience Scale-10 item, and Patient Health Questionnaire-9. The mediation analysis was conducted using the SPSS Process macro. RESULTS: Self-care ability was positively associated with social support (ß = .229) and resilience (ß = .290), and negatively associated with depression (ß = -.208). The relationship between social support and self-care ability was mediated by resilience and depression, respectively, and together in serial. The multiple mediating effects accounted for 34.0% of the total effect of social support on self-care ability. CONCLUSION: Our findings identify resilience and depression as multiple mediators between social support and self-care ability and highlight the important roles of social support, resilience and depression in improving self-care ability. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers should pay great attention to the underlying mechanisms of how social support affects patients' self-care ability during breast cancer rehabilitation. Integrated intervention programmes targeted at enhancing social support, building resilience and alleviating depression might be beneficial to the improvement of self-care ability. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. REPORTING METHOD: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross-sectional studies was applied to report the results.

The potential of antifungal peptides derived from Lactiplantibacillus plantarum WYH for biocontrol of Aspergillus flavus contamination.

Aspergillus flavus is a notorious fungus that contaminates food crops with toxic aflatoxins, posing a serious threat to human health and the agricultural economy. To overcome the inadequacy of traditional control methods and meet consumer preferences for natural-sources additives, there is an urgent demand for novel biocontrol agents that are safe and efficient. This study aims to investigate the antifungal properties of a novel antifungal agent derived from the biologically safe Lactiplantibacillus plantarum WYH. Firstly, antifungal peptides (AFPs) with a molecular weight of less than 3kD, exhibiting remarkable temperature stability and effectively retarding fungal growth in a dose-dependent manner specifically against A. flavus, were concentrated from the fermentation supernatant of L. plantarum WYH and were named as AFPs-WYH. Further analysis demonstrated that AFPs-WYH might exert antifungal effects through the induction of oxidative stress, disruption of mitochondrial function, alteration of membrane permeability, and cell apoptosis in A. flavus. To further validate our findings, a transcriptomics analysis was conducted on A. flavus treated with 2 and 5 mg/mL of AFPs-WYH, which elucidated the potential effect of AFPs-WYH administration on the regulation of genes involved in impairing fungal development and preventing aflatoxin biosynthesis pathways. Overall, AFPs-WYH reduced the A. flavus proliferation and affected the AFB1 biosynthesis, exhibiting a promising potential for food industry applications as a biopreservative and biocontrol agent.

Advance in Hippophae rhamnoides polysaccharides: Extraction, structural characteristics, pharmacological activity, structure-activity relationship and application.

Hippophae rhamnoides (Sea buckthorn) is an excellent medicinal and edible plant owing to its high nutritional and health-promoting properties. As an important bioactive component, H. rhamnoides polysaccharides (HRPs) have aroused wide attention due to their various pharmacological activities, including hepatoprotective, immuno-modulatory, anti-inflammatory, anti-oxidant, anti-tumor, hypoglycemic, anti-obesity, and so on. Nevertheless, the development and utilization of HRP-derived functional food and medicines are constrained to a lack of comprehensive understanding of the structure-activity relationship, application, and safety of HRPs. This review systematically summarizes the advancements on the extraction, purification, structural characteristics, pharmacological activities and mechanisms of HRPs. The structure-activity relationship, safety evaluation, application, as well as the shortcomings of current research and promising prospects are also highlighted. This article aims to offer a comprehensive understanding of HRPs and lay a groundwork for future research and utilization of HRPs as multifunctional biomaterials and therapeutic agents.

Toxicity, physiological response, and biosorption mechanism of Dunaliella salina to copper, lead, and cadmium.

Background: Heavy metal pollution has become a global problem, which urgently needed to be solved owing to its severe threat to water ecosystems and human health. Thus, the exploration and development of a simple, cost-effective and environmental-friendly technique to remove metal elements from contaminated water is of great importance. Algae are a kind of photosynthetic autotroph and exhibit excellent bioadsorption capacities, making them suitable for wastewater treatment. Methods: The effects of heavy metals (copper, lead and cadmium) on the growth, biomolecules accumulation, metabolic responses and antioxidant response of Dunaliella salina were investigated. Moreover, the Box-Behnken design (BBD) in response surface methodology (RSM) was used to optimize the biosorption capacity, and FT-IR was performed to explore the biosorption mechanism of D. salina on multiple heavy metals. Results: The growth of D. salina cells was significantly inhibited and the contents of intracellular photosynthetic pigments, polysaccharides and proteins were obviously reduced under different concentrations of Cu2+, Pb2+ and Cd2+, and the EC50 values were 18.14 mg/L, 160.37 mg/L and 3.32 mg/L at 72 h, respectively. Besides, the activities of antioxidant enzyme SOD and CAT in D. salina first increased, and then descended with increasing concentration of three metal ions, while MDA contents elevated continuously. Moreover, D. salina exhibited an excellent removal efficacy on three heavy metals. BBD assay revealed that the maximal removal rates for Cu2+, Pb2+, and Cd2+ were 88.9%, 87.2% and 72.9%, respectively under optimal adsorption conditions of pH 5-6, temperature 20-30°C, and adsorption time 6 h. Both surface biosorption and intracellular bioaccumulation mechanisms are involved in metal ions removal of D. salina. FT-IR spectrum exhibited the main functional groups including carboxyl (-COOH), hydroxyl (-OH), amino (-NH2), phosphate (-P=O) and sulfate (-S=O) are closely associated with the biosorption or removal of heavy metalsions. Discussion: Attributing to the brilliant biosorption capacity, Dunaliella salina may be developed to be an excellent adsorbent for heavy metals.

[Research progress on processing history evolution, chemical constituents, and pharmacological action of Scorpio].

Scorpio is a valuable Chinese animal medicine commonly used in clinical practice in China. It is the main drug in the treatment of liver wind internal movement caused by various reasons throughout the history of traditional Chinese medicine(TCM), with the effects of relieving wind and spasm, dredging collaterals, relieving pain, and eliminating toxin and mass. Scorpio is poisonous and often used as medicine after processing. There are records of its processing as early as the Song Dynasty. Afterward, there were more than 15 processing methods, including frying with vinegar, neat processing, and stir-frying. After processing, the fishy smell could be removed to correct the taste, and the toxicity could be reduced, which was beneficial to clinical application. At present, the main reported components in Scorpio are protein polypeptides, alkaloids, and lipids, with many pharmacological effects, such as anti-cancer, anti-coagulation, anti-thrombosis, anti-atherosclerosis, and anti-bacteria. In this study, the historical evolution of processing, chemical constituents, and pharmacological action of Scorpio were discussed in order to provide references for the related research on Scorpio.

Fructus mori: An Updated Review on Botany, Phytonutrient, Detection, Bioactivity, Quality Marker, and Application.

BACKGROUND: Fructus mori (mulberry) is not only a delicious fruit with rich phytonutrients and health functions but also a medicinal plant with many clinical therapeutic values for tonifying kidneys and consolidating essence, making hair black and eyes bright. METHODS: The related references about F. mori in this review from 1996 to 2022 had been collected from both online and offline databases, including PubMed, Elsevier, SciFinder, Willy, SciHub, Scopus, Web of Science, ScienceDirect, SpringerLink, Google Scholar, Baidu Scholar, ACS publications, and CNKI. The other information was acquired from ancient books and classical works about F. mori. RESULTS: An updated summary of phytonutrients from F. mori was listed as fellows: flavonoids (1-20) (23.5%), phenolic acids (21-34) 16.5%), alkaloids (35-75) (48.2%), polysaccharides (76- 78) (3.5%), other compounds (79-85) (8.3%). The above chemical components were detected by TLC, UV-Vis, HPLC, GC-MS, and AAS methods for their quality standards. The various bioactivities (hepatoprotective, immunomodulatory, anti-oxidant, hypoglycemic, anti-cancer, and other activities) of mulberry are summarized and discussed in this review, which laid an important basis for analyzing their mechanisms and quality markers. This review summarized its applications for vinegar, wine, yogurt, drink, jelly, and sweetmeat in food fields, and the existing problems and future development directions are also discussed in this review. CONCLUSIONS: This review made a comprehensive description of F. mori, including botany, phytonutrient, detection, bioactivity, quality marker, and application. It will not only provide some important clues for further studying F. mori, but also provide some valuable suggestions for indepth research and development of F. mori.

Macrophage KLF15 prevents foam cell formation and atherosclerosis via transcriptional suppression of OLR-1.

BACKGROUND: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis. METHODS: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE-/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively. RESULTS: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis. CONCLUSION: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis.

[Role of autophagy in cadmium-induced damage to the blood-testis barrier in mice].

OBJECTIVE: To investigate the role of autophagy in cadmium chloride (CdCl2)-induced damage to the blood-testis barrier (BTB) in mice. METHODS: Twenty four-week-old male C57BL/6 mice were randomly divided into four groups and intraperitoneally injected with CdCl2 at 0 mg/kg/d (the control), 0.5 mg/kg/d (low-dose), 1.0 mg/kg/d (medium-dose) and 2.0 mg/kg/d (high-dose) respectively for 28 consecutive days. Then the morphological changes of the testis tissue was observed by HE staining, the integrity of BTB measured with the biotracer, and the expressions of the BTB components ZO-1 and N-Cadherin proteins detected by Western blot. The TM4 Sertoli cells were treated with CdCl2at 0, 2.5, 5 and 10 µmol/L respectively for 24 hours, followed by determination of the expression levels of ZO-1 and N-Cadherin as well as the autophagy-related proteins LC3II and p62. Then the cells were again treated with CdCl2 in the presence of the autophagy inhibitor chloroquine (CQ) at 5 µmol/L or the autophagy inducer rapamycin (Rap) at 50 nmol/L for 24 hours, followed by measurement of the expressions of LC3II, p62, ZO-1 and N-Cadherin by Western blot. RESULTS: Compared with the control group, the cadmium-exposed mice showed increased interstitial space in the seminiferous tubules, formation of intracellular cavitation in the germ cells with decreased layers and disordered arrangement, and damaged integrity of the BTB. The expressions of the ZO-1 and N-Cadherin proteins were significantly down-regulated in the testis tissue of the mice in the medium- and high-dose CdCl2 groups (P < 0.05), and even more significantly in the CdCl2-exposed cells in comparison with those in the control mice (P < 0.01), while the expressions of the LC3II and p62 proteins were remarkably up-regulated (P < 0.05). The expressions of ZO-1, N-Cadherin, LC3II and p62 were also up-regulated in the cells co-treated with CQ and CdCl2 (P < 0.01), those of ZO-1, N-Cadherin and p62 down-regulated (P< 0.05) and that of LC3II up-regulated (P < 0.05) in the cells co-treated with Rap and CdCl2. CONCLUSION: CdCl2 can damage the integrity of the mouse BTB, which may be attributed to its ability to enhance the autophagy in Sertoli cells and regulate the expressions of BTB proteins.

Two-Fold ND5 Genes, Three-Fold Control Regions, lncRNA, and the "Missing" ATP8 Found in the Mitogenomes of Polypedates megacephalus (Rhacophridae: Polypedates).

In prior research on the mitochondrial genome (mitogenome) of Polypedates megacephalus, the one copy of ND5 gene was translocated to the control region (CR) and the ATP8 gene was not found. Gene loss is uncommon among vertebrates. However, in this study, we resequenced the mitogenomes of P. megacephalus from different regions using a "primer bridging" approach with Sanger sequencing technologies, which revealed the "missing" ATP8 gene in P. megacephalus as well as three other previously published Polypedates. The mitogenome of this species was found to contain two copies of the ND5 genes and three copies of the control regions. Furthermore, multiple tandem repeats were identified in the control regions. Notably, we observed that there was no correlation between genetic divergence and geographic distance. However, using the mitogenome, gene expression analysis was performed via RT-qPCR of liver samples and it was thus determined that COIII, ND2, ND4, and ND6 were reduced to 0.64 ± 0.24, 0.55 ± 0.34, 0.44 ± 0.21 and 0.65 ± 0.17, respectively, under low-temperature stress (8 °C) as compared with controls (p < 0.05). Remarkably, the transcript of long non-coding RNA (lncRNA) between positions 8029 and 8612 decreased significantly with exposure to low-temperature stress (8 °C). Antisense ND6 gene expression showed a downward trend, but this was not significant. These results reveal that modulations of protein-coding mitochondrial genes and lncRNAs of P. megacephalus play a crucial role in the molecular response to cold stress.

Probiotic Potential, Antibacterial, and Antioxidant Capacity of Aspergillus luchuensis YZ-1 Isolated From Liubao Tea.

Aspergillus fungi are widely used in the traditional fermentation of food products, so their safety risks and functions are worthy of investigation. In this study, one Aspergillus luchuensis YZ-1 isolated from Liubao tea was identified based on phylogenetic analyses of sequences of three genes coding for internal transcribed spacer 1 (ITS1), ß-tubulin (benA), and calmodulin (CaM). The results of hemolytic activity, DNase activity, cytotoxicity assay, and antibiotic resistance assay indicated that the strain is potentially safe. The excellent gastrointestinal fluid tolerance, acid tolerance, bile tolerance, auto-aggregation, co-aggregation, cell surface hydrophobicity, and adhesion to human colon adenocarcinoma (HT29) cell line were observed on analysis of the probiotic properties. Furthermore, the results of the antibacterial activity of A. luchuensis YZ-1 indicated that the strain had strong antagonistic effects against Gram-negative and Gram-positive bacteria as well as fungi. Simultaneously, the water extracts and 80% ethanolic extracts of A. luchuensis YZ-1 cells also showed strong ABTS, DPPH, and OH- scavenging ability. Taken together, our results suggest that A. luchuensis YZ-1 has desirable functional probiotic properties and can be proposed as a biocontrol agent in the food industry.

Mutant IAA21 genes from Dendrocalamus sinicus Chia et J. L. Sun inhibit stem and root growth in transgenic tobacco by interacting with ARF5.

Woody bamboos are important resource of industrial fibres. Auxin signaling plays a key role in multiple plant developmental processes, as yet the role of auxin/indole acetic acid (Aux/IAA) in culm development of woody bamboos has not been previously characterized. Dendrocalamus sinicus Chia et J. L. Sun is the largest woody bamboo documented in the world. Here, we identified two alleles of DsIAA21 gene (sIAA21 and bIAA21) from the straight- and bent-culm variants of D. sinicus, respectively, and studied how the domains I, i, and II of DsIAA21 affect the gene transcriptional repression. The results showed that bIAA21 expression was rapidly induced by exogenous auxin in D. sinicus. In transgenic tobacco, sIAA21 and bIAA21 mutated in domains i, and II significantly regulated plant architecture and root development. Stem cross sections revealed that parenchyma cells were smaller in transgenic plants than that in wild type plants. Domain i mutation changed the leucine and proline at position 45 to proline and leucine (siaa21L45P and biaa21P45L) strongly repressed cell expansion and root elongation by reducing the gravitropic response. Substitution of isoleucine with valine in domain II of the full length DsIAA21 resulted in dwarf stature in transgenic tobacco plants. Furthermore, the DsIAA21 interacted with auxin response factor 5 (ARF5) in transgenic tobacco plants, suggesting that DsIAA21 might inhibit stem and root elongation via interacting with ARF5. Taken together, our data indicated that DsIAA21 was a negative regulator of plant development and suggested that amino acid differences in domain i of sIAA21 versus bIAA21 affected their response to auxin, and might play a key role in the formation of the bent culm variant in D. sinicus. Our results not only shed a light on the morphogenetic mechanism in D. sinicus, but also provided new insights into versatile function of Aux/IAAs in plants.

[Research progress on processing historical evolution, chemical constituents, and pharmacological action of Bombyx Batryticatus].

Bombyx Batryticatus is a precious traditional Chinese animal drug commonly used in clinical practice in China, which has the effects of extinguishing wind, stopping convulsions, dispelling wind, relieving pain, resolving phlegm, and dissipating mass. The processing of Bombyx Batryticatus has a long history. As early as in the Liu Song period of the Southern and Northern Dynasties, there was a record of the processing of Bombyx Batryticatus with rice swill. In addition to the processing with bran, honey bran, and ginger juice, which are still used today, there are also processing methods such as rendering, flour processing, wine processing, salt processing, oil processing, charcoal, and red dates processing in ancient times. After processing, the fishy smell of Bombyx Batryticatus can be removed, and avoid nausea and vomiting caused by the direct taking. Furthermore, processing can also facilitate the removal of surface hairs and toxicity reduction, making the medicinal material crispy and easy to crush. Previous studies have shown that the main chemical constituents of Bombyx Batryticatus include protein polypeptides, sterols, and flavonoids, with anticonvulsant, anticoagulation, antithrombotic, anti-cancer, hypnotic, hypoglycemic, and other pharmacological effects. This paper reviewed the processing historical evolution, chemical constituents, and pharmacological effects of Bombyx Batryticatus to lay a foundation for the research on the processing mechanism, quality control, and active core substances of Bombyx Batryticatus.

Peganum harmala L.: A Review of Botany, Traditional Use, Phytochemistry, Pharmacology, Quality marker, and Toxicity.

BACKGROUND: Peganum harmala L. is a perennial herb of Peganum in Zygophyllaceae family. It has been used as a national medicinal herb with the efficacy of strengthening muscle, warming stomach, dispelling cold, and removing dampness in Chinese folk. Clinically, it is mainly used to treat diseases such as weak muscles and veins, joint pain, cough and phlegm, dizziness, headache, and irregular menstruation. METHODS: The relevant information about P. harmala L. in this review is based on online databases, including Elsevier, Willy, Web of Science, PubMed, ScienceDirect, SciFinder, SpringLink, Google Scholar, Baidu Scholar, ACS publications, SciHub, Scopus, and CNKI. The other information was acquired from ancient books and classical works about P. harmala L. RESULTS: P. harmala L. is an important medicinal plant with a variety of traditional uses according to the theory of Chinese medicine. Phytochemical research revealed that P. harmala L. contained alkaloids, volatile oils, flavonoids, triterpenoids, coumarins, lignins, anthraquinones. Modern studies showed P. harmala L. possessed multiple bioactivities, including anti-cancer, neuroprotective, anti-bacterial, anti-inflammatory, hypoglycemic, anti-hypertensive, anti-asthmatic, and insecticidal activities. Furthermore, the contents of the quality marker and toxicity of P. harmala L. were summarized and analyzed in this review. CONCLUSION: The botany, traditional use, phytochemistry, pharmacology, quality marker, and toxicity of P. harmala L. were reviewed in this paper. It will not only provide an important clue for further studying P. harmala L., but also supply an important theoretical basis and valuable reference for in-depth research and exploitations of this plant in the future.

A Scoring System to Select the Candidates for Adjuvant Chemotherapy Alone in High-Risk Early-Stage Cervical Cancer Patients With Pelvic Lymph Node Metastases After Surgery.

BACKGROUND: The aim was to build a risk scoring system to guide the adjuvant treatment for early-stage cervical cancer patients with pelvic lymph node (LN) metastases after surgery. METHODS: A cohort of 1213 early-stage cervical cancer patients with pelvic LN metastases (T1-2aN1M0) were selected from the NCI SEER database, of which 1040 patients received adjuvant external beam radiotherapy concurrent with chemotherapy (EBRT+Chemo) and 173 patients received adjuvant chemotherapy alone. The Cox regression analysis was applied to identify the risk factors associated with worse survival. The exp (ß) of each independent risk factors from multivariate analysis was assigned to develop the risk scoring system. The total cohort was divided into different risk subgroups accordingly and the efficacy of different adjuvant modalities in each risk subgroups was compared. RESULTS: The patients were divided into 3 risk subgroups (Low-risk: total score <7.20, Middle-risk:7.20≤ total score≤ 8.40, High-risk: total score<8.40) based on the scoring system incorporating 5 independent risk factors. The survival analysis suggested that low-risk (hazard ratio [HR]=1.046, 95% CI: 0.586-1.867; P= 0.879) and middle-risk patients (HR=0.709, 95% CI: 0.459-1.096; P =0.122) could not benefit more from EBRT+Chemo than Chemo alone. However, EBRT+Chemo remained the superiority to Chemo alone in the high-risk subgroup (HR=0.482, 95% CI: 0.294-0.791; P =0.003). CONCLUSION: A risk scoring system has been built to direct the adjuvant treatment for early-stage cervical cancer patients with pelvic LN metastases after surgery, where Chemo alone was totally enough for low-risk and middle-risk patients stratified by the model while EBRT+Chemo was still recommended for patients in the high-risk subgroup.

A population-based risk scoring system to individualize adjuvant treatment for stage IIIC endometrial cancer patients after surgery.

BACKGROUND: To develop a risk scoring system to tailor the adjuvant treatment for stage IIIC EC patients after surgery. METHODS: Data source was from the Surveillance, Epidemiology, and End Results (SEER) registry, where 3251 post-operative stage IIIC EC patients with different adjuvant treatment were included. Cox regression analysis was used to identify risk factors. The exp (ß) of each independent risk factors generating from the cox analysis was used to construct the risk scoring system, which was further utilized to divide the patients into different risk subgroups and the efficacy of different adjuvant modalities in each risk subgroups would be compared accordingly. RESULTS: Six independent risk factors were identified to develop the scoring system, which further divided the patients into three risk subgroups based on the total risk score (Low-risk≤8.46, 8.47 ≤ Middle-risk≤9.94, High-risk≥9.95). This study revealed that CRT was not superior to RT alone (HR:1.208, 95%CI: 0.852-1.741; P = 0.289) or CT alone (HR:1.260, 95%CI: 0.750-2.116; P = 0.382) in Low-risk subgroup. We also observed that CRT had a survival advantage over other treatment modalities in the Middle-risk subgroup (All P < 0.001), but CRT and CT alone to be superimposable in the High-risk subgroup (HR: 1.395, 95%CI: 0.878-2.216; P = 0.159). CONCLUSION: A risk scoring system has been developed to tailor the adjuvant treatment for stage IIIC EC patients after surgery, where RT or CT alone could be a substitute for CRT in Low-risk patients and CT alone was a potential alternative for High-risk patients while CRT remained to be the optimal choice for the Middle-risk patients.

[Research progress on processing history evolution, chemical constituents, and pharmacological effects of Hirudo].

As a traditional animal drug, Hirudo is slightly toxic and has the effects of breaking blood stasis, dredging meridians, expelling stasis, and resolving mass. It has a long history of processing, and the early boiling records can be traced back to the Han Dynasty. More than ten processing methods such as frying, roasting, and lime processing appeared later. After processing, Hirudo is deodorized and modified in taste and becomes crispy, which is conducive to crushing and clinical application. At present, the reported components in Hirudo mainly include protein polypeptides, pteridines, and lipids, which have anti-coagulant, anti-thrombotic, anti-atherosclerotic, anti-tumor, and other pharmacological effects. This study reviewed the processing history evolution, chemical consti-tuents, and pharmacological effects of Hirudo to provide a reference for the related research on Hirudo.

One-pot synthesis and enzyme-responsiveness of amphiphilic doxorubicin prodrug nanomicelles for cancer therapeutics.

In this study, we report a one-pot synthesis and enzyme-responsiveness of polyethylene glycol (PEG) and glutamic acid (Glu)-based amphiphilic doxorubicin (DOX) prodrug nanomicelles for cancer therapeutics. The nanomicelles were accomplished by esterification and amidation reactions. The nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) data confirmed the structure of nanomicelles. The DOX-loaded nanomicelles showed a DLS-measured average size of 107 nm and excellent stability in phosphate-buffered saline (PBS) for 7 days. The drug loading and cumulative release rates were measured by ultraviolet-visible (UV-vis) spectrophotometry at 481 nm. The cumulative release rate could reach 100% in an enzyme-rich environment. Further, the therapeutic efficiency of nanomicelles to cancer cells was determined by cell viability and cellular uptake and distribution using HeLa cells. The cell viability study showed that the DOX-loaded nanomicelles could effectively inhibit the HeLa cell proliferation. The cellular uptake study confirmed that the nanomicelles could be effectively ingested by HeLa cells and distributed into cell nuclei. Based on the collective experimental data, this study demonstrated that the synthesized nanomicellar prodrug of DOX is a potential candidate for cancer therapeutics.

Prognostic model for the exemption of adjuvant chemotherapy in stage IIIC endometrial cancer patients.

Background: This study aimed to develop a nomogram to predict the survival for stage IIIC endometrial cancer (EC) patients with adjuvant radiotherapy (ART) alone and personalize recommendations for the following adjuvant chemotherapy (ACT). Methods: In total, 746 stage IIIC EC patients with ART alone were selected from the Surveillance, Epidemiology, and End Results (SEER) registry. Cox regression analysis was performed to identify independent risk factors. A nomogram was developed accordingly, and the area under the receiver operating characteristic curve (AUC) and C-index were implemented to assess the predictive power. The patients were divided into different risk strata based on the total points derived from the nomogram, and survival probability was compared between each risk stratus and another SEER-based cohort of stage IIIC EC patients receiving ART+ACT (cohort ART+ACT). Results: Five independent predictors were included in the model, which had favorable discriminative power both in the training (C-index: 0.732; 95% CI: 0.704-0.760) and validation cohorts (C-index: 0.731; 95% CI: 0.709-0.753). The patients were divided into three risk strata (low risk <135, 135 ≤ middle risk ≤205, and high risk >205), where low-risk patients had survival advantages over patients from cohort ART+ACT (HR: 0.45, 95% CI: 0.33-0.61, P < 0.001). However, the middle- and high-risk patients were inferior to patients from cohort ART+ACT in survival (P < 0.001). Conclusion: A nomogram was developed to exclusively predict the survival for stage IIIC EC patients with ART alone, based on which the low-risk patients might be perfect candidates to omit the following ACT. However, the middle- and high-risk patients would benefit from the following ACT.

Bacteroides fragilis ameliorates Cronobacter malonaticus lipopolysaccharide-induced pathological injury through modulation of the intestinal microbiota.

Cronobacter has attracted considerable attention due to its association with meningitis and necrotizing enterocolitis (NEC) in newborns. Generally, lipopolysaccharide (LPS) facilitates bacterial translocation along with inflammatory responses as an endotoxin; however, the pathogenicity of Cronobacter LPS and the strategies to alleviate the toxicity were largely unknown. In this study, inflammatory responses were stimulated by intraperitoneal injection of Cronobacter malonaticus LPS into Sprague-Dawley young rats. Simultaneously, Bacteroides fragilis NCTC9343 were continuously fed through gavage for 5 days before or after injection of C. malonaticus LPS to evaluate the intervention effect of B. fragilis. We first checked the morphological changes of the ileum and colon and the intestinal microbiota and then detected the generation of inflammatory factors, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and interleukin-10 (IL-10) and the expression of Toll-like receptor 4 (TLR4), occludin, claudin-4, and iNOs. The results indicated that C. malonaticus LPS exacerbated intestinal infection by altering gut microbe profile, tight junction protein expression, and releasing inflammatory factors in a time- and dose-dependent manner. Intriguingly, treatment with B. fragilis obviously diminished the pathological injuries and expression of TLR4 caused by C. malonaticus LPS while increasing gut microbes like Prevotella-9. We note that Shigella, Peptoclostridium, and Sutterella might be positively related to C. malonaticus LPS infection, but Prevotella-9 was negatively correlated. The results suggested that the intestinal microbiota is an important target for the prevention and treatment of pathogenic injuries induced by C. malonaticus LPS.

[The Clinical Significance of Oligoclonal Bands in Patient with Multiple Myeloma].

OBJECTIVE: To investigate the clinical value of oligoclonal bands (OB) in patients with multiple myeloma (MM). METHODS: The laboratory test and clinical data of 624 newly diagnosed MM patients admitted to Blood Diseases Hospital of Chinese Academy of Medical Sciences from January 2013 to December 2019 were retrospectively analyzed, including 30 patients with OB, and the clinical characteristics, treatment effects and survival of OB and non-OB patients were analyzed and compared. RESULTS: OB occurred in 11.8% (22/187) of patients who received autologous stem cell transplantation(ASCT) and only 1.8% (8/437) of patients who did not receive ASCT (P=0.000). The median time to the appearance of oligoclonal bands was 3.2(0.6-10.5) months after transplantation. The M protein types of oligoclonal bands mainly include IgG κ, IgG λ, IgM λ and λ light chains. In the presence of oligoclonal bands, 90% of patients were evaluated as complete remission (CR) and above. There were no statistically significant differences in disease stage, tumor burden, and genetic abnormalities between OB and non-OB patients. Among the all patients, the prognosis of OB patients was significantly better than that of non-OB patients, and OB patients showed deeper disease remission (significantly higher CR rate, MRD negative rate, and longer MRD negative duration). Among patients who underwent ASCT, OB patients showed earlier immune recovery, but the depth of treatment response and survival outcomes were similar between OB and non-OB patients, it was no statistically difference. Although OB patients showed earlier immune reconstitution, this did not translate into better survival, suggesting that the better prognosis of OB patients was mainly related to deeper and durable remission rather than early immune reconstitution. Further analysis in patients who received ASCT and obtained MRD negative indicated that there was no additional survival benefit in patients with OB. CONCLUSION: The better prognosis of OB patients may be related to the deeper treatment response, but not to the early immune reconstitution. The appearance of OB is only a sign of deep remission and early immune reconstitution in patients, it cannot be translated into survival benefit of MM patients.