Sandwich-Structured Implants to Obstruct Multipath Energy Supply and Trigger Self-Enhanced Hypoxia-Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis.

As a currently common strategy to treat cancer, surgical resection may cause tumor recurrence and metastasis due to residual postoperative tumors. Herein, an implantable sandwich-structured dual-drug depot is developed to trigger a self-intensified starvation therapy and hypoxia-induced chemotherapy sequentially. The two outer layers are 3D-printed using a calcium-crosslinked mixture ink containing soy protein isolate, polyvinyl alcohol, sodium alginate, and combretastatin A4 phosphate (CA4P). The inner layer is one patch of poly (lactic-co-glycolic acid)-based electrospun fibers loaded with tirapazamine (TPZ). The preferentially released CA4P destroys the preexisting blood vessels and prevents neovascularization, which obstructs the external energy supply to cancer cells but aggravates hypoxic condition. The subsequently released TPZ is bioreduced to cytotoxic benzotriazinyl under hypoxia, further damaging DNA, generating reactive oxygen species, disrupting mitochondria, and downregulating hypoxia-inducible factor 1α, vascular endothelial growth factor, and matrix metalloproteinase 9. Together these processes induce apoptosis, block the intracellular energy supply, counteract the disadvantage of CA4P in favoring intratumor angiogenesis, and suppress tumor metastasis. The in vivo and in vitro results and the transcriptome analysis demonstrate that the postsurgical adjuvant treatment with the dual-drug-loaded sandwich-like implants efficiently inhibits tumor recurrence and metastasis, showing great potential for clinical translation.

Construction and validation of prognostic scoring models to risk stratify patients with acquired immune deficiency syndrome-related diffuse large B cell lymphoma.

Acquired immune deficiency syndrome (AIDS)-related diffuse large B cell lymphoma (AR-DLBCL) is a rare disease with a high risk of mortality. There is no specific prognostic model for patients with AR-DLBCL. A total of 100 patients diagnosed with AR-DLBCL were enrolled in our study. Clinical features and prognostic factors for overall survival (OS) and progression-free survival (PFS) were evaluated by univariate and multivariate analyses. Central nervous system (CNS) involvement, opportunistic infection (OI) at lymphoma diagnosis, and elevated lactate dehydrogenase (LDH) were selected to construct the OS model; CNS involvement, OI at lymphoma diagnosis, elevated LDH, and over four chemotherapy cycles were selected to construct the PFS model. The area under the curve and C-index of GZMU OS and PFS models were 0.786/0.712; 0.829/0.733, respectively. The models we constructed showed better risk stratification than International Prognostic Index (IPI), age-adjusted IPI, and National Comprehensive Cancer Network-IPI. Furthermore, in combined cohort, the Hosmer-Lemeshow test showed that the models were good fits (OS: p = 0.8244; PFS: p = 0.9968) and the decision curve analysis demonstrated a significantly better net benefit. The prognostic efficacy of the proposed models was validated independently and outperformed the currently available prognostic tools. These novel prognostic models will help to tackle a clinically relevant unmet need.

Research progress in the treatment of Alzheimer's disease by regulating brain-gut-microbiome axis with "Sanjiao" acupuncture method / 中华老年医学杂志

Recent studies have found that the brain-gut-microbiome axis(BGMA)is closely related to the occurrence and development of Alzheimer's disease(AD). BGMA can affect AD in various aspects such as neuro-immune regulation and intestinal microflora, and is a potential new target for the treatment of AD.The "Sanjiao" acupuncture method is proposed by professor Han Jingxian, a famous Chinese medicine practitioner, based on his theory of "dysfunction of Qi activity of Sanjiao leads to aging" , and has been widely used in the treatment of AD and other age-related diseases in clinical practice.This article reviews the theory of "dysfunction of Qi activity of Sanjiao leads to aging" and the relationship between the "Sanjiao" acupuncture method and BGMA, with the hope that the "San Jiao" acupuncture method can become a new target for treatment of AD in the future.

HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems / 中华预防医学杂志

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

Yoga Therapy During Chemotherapy for Early-Stage and Locally Advanced Breast Cancer.

BACKGROUND: Chemotherapy is associated with decreased quality of life (QOL), fatigue, depression, and weight gain in patients with breast cancer. Weight gain is associated with poorer prognosis. Yoga improves QOL, fatigue, and mood in women with breast cancer but its effect on treatment-related weight gain has not been studied. The aim of this trial was to determine the feasibility of personalized yoga therapy in women receiving treatment for early-stage or locally advanced breast cancer and assess its impact on weight gain. METHODS: Thirty women were randomized 1:1 to receive yoga therapy by a certified yoga therapist during treatment or a control group. Participants in the yoga arm were asked to complete three 30 minute yoga sessions weekly (which included movement, breath work, mindfulness, and relaxation) throughout adjuvant or neoadjuvant chemotherapy (N = 29) or endocrine (N = 1); the control arm received breast cancer treatment without yoga. For comparability between participants randomized to yoga therapy, the single patient treated with endocrine therapy was excluded from the analysis. Primary outcomes were feasibility and weight change. Additional outcomes were mood, fatigue, QOL, serum tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP) as immune mediator biomarkers. RESULTS: Mean age was 51.6 years, 75.9% were white and 24.1% were people of color, reflecting the cancer center population. 80% had stage II-III disease. Enrollment was completed in 9 months. Compliance was lower than predicted; however, participants participated in on average 1.7 yoga sessions/week for a mean 15.6 weeks duration. There were no adverse events. Control arm participants gained on average 2.63% body weight during treatment while yoga participants lost 0.14% body weight (weight change = -0.36 in yoga arm vs. 2.89 in standard of care arm, Wilcoxon rank sum test P = .024). Control participants reported increased fatigue and decreased QOL, while yoga participants reported no change in QOL. No significant change in TNF-alpha or CRP was noted in either arm. CONCLUSION: This feasibility study suggests that personalized yoga therapy is beneficial for QOL and weight maintenance among women undergoing chemotherapy for early-stage or locally advanced breast cancer. Weight maintenance associated with yoga therapy may be of clinical significance in this population given the poorer prognosis associated with weight gain in breast cancer survivors. TRIAL REGISTRATION: NIH Clinicaltrials.gov #NCT03262831; August 25, 2017. https://clinicaltrials.gov/ct2/show/NCT03262831.

Genome-wide identification and analysis of bZIP gene family reveal their roles during development and drought stress in Wheel Wingnut (Cyclocarya paliurus).

BACKGROUND: The bZIP gene family has important roles in various biological processes, including development and stress responses. However, little information about this gene family is available for Wheel Wingnut (Cyclocarya paliurus).  RESULTS: In this study, we identified 58 bZIP genes in the C. paliurus genome and analyzed phylogenetic relationships, chromosomal locations, gene structure, collinearity, and gene expression profiles. The 58 bZIP genes could be divided into 11 groups and were unevenly distributed among 16 C. paliurus chromosomes. An analysis of cis-regulatory elements indicated that bZIP promoters were associated with phytohormones and stress responses. The expression patterns of bZIP genes in leaves differed among developmental stages. In addition, several bZIP members were differentially expressed under drought stress. These expression patterns were verified by RT-qPCR. CONCLUSIONS: Our results provide insights into the evolutionary history of the bZIP gene family in C. paliurus and the function of these genes during leaf development and in the response to drought stress. In addition to basic genomic information, our results provide a theoretical basis for further studies aimed at improving growth and stress resistance in C. paliurus, an important medicinal plant.

Plant Virome Analysis by the Deep Sequencing of Small RNAs of Fritillaria thunbergii var. chekiangensis and the Rapid Identification of Viruses.

Thunberg fritillary (Fritillaria thunbergii), a perennial used in traditional Chinese herbal medicine, is a members of the family Liliaceae. The degeneration of germplasm is a severe problem in the production of Fritillaria thunbergii var. chekiangensis. However, no information about viral infections of F. thunbergii var. chekiangensis has been reported. In this study, we sequenced the small RNAs of F. thunbergii var. chekiangensis from leaves and bulbs, and viruses were identified using a phylogenetic analysis and BLAST search for sequence. In addition, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) was used to rapidly detect viruses in this variety. Our study first reported that five viruses infected F. thunbergii var. chekiangensis. Among them, fritillary virus Y (FVY), lily mottle virus (LMoV), Thunberg fritillary mosaic virus (TFMV), and hop yellow virus (HYV) had been reported in F. thunbergii, while apple stem grooving virus was first reported in the genus Fritillaria. A multiplex RT-PCR method was developed to rapidly test the four viruses FVY, LMoV, TFMV, and HYV in F. thunbergii var. chekiangensis. Our results provide a better understanding of the infection of F. thunbergii var. chekiangensis by viruses and a basic reference for the better design of suitable control measures.

In vivo identification of the pharmacodynamic ingredients of Polygonum cuspidatum for remedying the mitochondria to alleviate metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic liver disease that currently lacks approved pharmacological treatment options. The mechanisms and active ingredients of Polygonum cuspidatum (PC) that regulate the mitochondria to relieve MAFLD have not been assessed. Thus, this study was designed to explore the bioactive components of PC extract in regulating mitochondria to alleviate high-fat diet-induced MAFLD using mitochondrial pharmacology and pharmacochemistry. Our results demonstrate that PC protected the mitochondrial ultrastructure and inhibited oxidative stress and energy metabolism disorder in the liver mitochondria. Furthermore, PC-derived components in the liver mitochondria attenuated oxidative stress and restored the energy metabolism of fat emulsion-induced steatosis in L02 cell. Sixteen compounds were identified in the liver-mitochondrial extracts of PC-treated rats. The antisteatotic effects of three identified monomers and anti-MAFLD ability of the monomer group were confirmed. Collectively, our data suggest that the extract of PC can alleviate lipid metabolism disorder in MAFLD by protecting the mitochondrial ultrastructure, reducing oxidative stress injury, and promoting energy metabolism. The sixteen identified compounds were potentially the main effective ingredients of PC in treating MAFLD. Thus, PC shows potential in treating MAFLD and related mitochondrial dysfunction. The proposed strategy to identify the ingredients of herbal medicines based on mitochondrial pharmacology and pharmacochemistry presents a new approach in exploring the pharmacodynamic components of herbal medicines that regulate mitochondria in preventing and treating diseases.

Insights into Pyrroloquinoline Quinone (PQQ) Effects on Soil Nutrients and Pathogens from Pepper Monocropping Soil under Anaerobic and Aerobic Conditions.

Imbalances of soil available nutrients and soilborne diseases have seriously restricted the productivity of crops and jeopardized food security worldwide. Pyrroloquinoline quinone (PQQ), a redox cofactor in some bacteria involved in glucose metabolism and phosphorus mineralization, could be anticipated to alter soil ecosystems to a certain extent. However, there is limited information on PQQ defending soilborne pathogens and regulating soil main nutrients. Here, a pot experiment based on mono-cropping soils of pepper was conducted to examine the effects of PQQ amendment on reconstructing soil microbial communities and soil nutrients under aerobic/anaerobic conditions comprising three treatments, namely, control, PQQ (aerobic), and FL-PQQ (anaerobic). The results revealed that soil microbial community composition and soil nutrients were distinctly altered by PQQ regimes. Compared to control, PQQ treatment significantly increased the content of soil available phosphorus (AP), while FL_PQQ treatment strongly improved the content of soil available nitrogen (AN). In terms of pathogens, relative to control, both PQQ treatments suppressed the abundances of pathogens, of which FL_PQQ treatment significantly decreased the abundance of the pathotrophic fungal by 64% and the abundance of Fusarium oxysporum by 57%, largely attributed to the increase of organic acid generators (Oxobacter, Hydrogenispora) and potential antagonists (Bacillus, Talaromyces). Structural equation modeling (SEM) showed that PQQ regimes suppressed pathogens by indirectly regulating soil physicochemical properties and microbial communities. Overall, we proposed that PQQ application both in aerobic/anaerobic conditions could improve soil available nutrients and suppress soil pathogens in pepper monocropping soils. IMPORTANCE The attention to PQQ (pyrroloquinoline quinone) effect on soil nutrients and pathogens was less paid in monocropping soils. However, the underlying microbial interacting mechanism remains unclear. Adopting a novel external bio-additive, the effects of PQQ on soil main nutrients and the pathotrophic fungal under aerobic and anaerobic regimes will be investigated, which would help to improve soil quality health. Our main conclusion was that PQQ would help to remediate monocropping obstacle soils in terms of soil nutrients and soil pathogens by associating with the microbial community, and anaerobic PQQ application more favored amelioration of continuous obstacle soils. These results will benefit the health and sustainable development of pepper production as well as other greenhouse vegetable production.

A randomized feasibility study evaluating temozolomide circadian medicine in patients with glioma.

Background: Gliomas are the most common primary brain tumor in adults. Current treatments involve surgery, radiation, and temozolomide (TMZ) chemotherapy; however, prognosis remains poor and new approaches are required. Circadian medicine aims to maximize treatment efficacy and/or minimize toxicity by timed delivery of medications in accordance with the daily rhythms of the patient. We published a retrospective study showing greater anti-tumor efficacy for the morning, relative to the evening, administration of TMZ in patients with glioblastoma. We conducted this prospective randomized trial to determine the feasibility, and potential clinical impact, of TMZ chronotherapy in patients with gliomas (NCT02781792). Methods: Adult patients with gliomas (WHO grade II-IV) were enrolled prior to initiation of monthly TMZ therapy and were randomized to receive TMZ either in the morning (AM) before 10 am or in the evening (PM) after 8 pm. Pill diaries were recorded to measure compliance and FACT-Br quality of life (QoL) surveys were completed throughout treatment. Study compliance, adverse events (AE), and overall survival were compared between the two arms. Results: A total of 35 evaluable patients, including 21 with GBM, were analyzed (18 AM patients and 17 PM patients). Compliance data demonstrated the feasibility of timed TMZ dosing. There were no significant differences in AEs, QoL, or survival between the arms. Conclusions: Chronotherapy with TMZ is feasible. A larger study is needed to validate the effect of chronotherapy on clinical efficacy.

Phytoestrogen arctigenin preserves the mucus barrier in inflammatory bowel diseases by inhibiting goblet cell apoptosis via the ERß/TRIM21/PHB1 pathway.

Intestinal mucus barrier dysfunction is closely involved in the pathogenesis of inflammatory bowel diseases (IBD). To investigate the protective effect and underlying mechanism of arctigenin, a phytoestrogen isolated from the fruits of Arctium lappa L., on the intestinal mucus barrier under colitis condition. The role of arctigenin on the intestinal mucus barrier and the apoptosis of goblet cells were examined by using both in vitro and in vivo assays. Arctigenin was demonstrated to promote the mucus secretion and maintain the integrity of mucus barrier, which might be achieved by an increase in the number of goblet cells via inhibiting apoptosis. Arctigenin selectively inhibited the mitochondrial pathway-mediated apoptosis. Moreover, arctigenin elevated the protein level of prohibitin 1 (PHB1) through blocking the ubiquitination via activation of estrogen receptor ß (ERß) to competitively interact with PHB1 and disrupt the binding of tripartite motif 21 (TRIM21) with PHB1. ERß knock down in the colons of mice with DSS-induced colitis resulted in significant reduction of the protection of arctigenin and DPN against the mucosal barrier. Arctigenin can maintain the integrity of the mucus barrier by inhibiting the apoptosis of goblet cells through the ERß/TRIM21/PHB1 pathway.

"Fenestration and Tunnel Method" a Modification for the Holmium Laser Transurethral Prostatectomy of Large-Volume Prostates >80 ml: A Retrospective Study Based on 1-Year Follow-Up.

The purpose of this study was to promote the holmium laser enucleation of the prostate (HoLEP) technology for large-volume prostates (>80 ml) and compare it with the traditional method, we modified the technique and applied this technology to clinical practice. A retrospective study comprising 118 patients who underwent HoLEP surgery from February 2018 to December 2019 was conducted in our center. Group A consisted of 57 patients with large-volume prostate (>80 ml) who received modified "fenestration and tunnel method" from February 2019 till December 2019, while group B consisted of 61 patients who received the traditional trivalvular operation method from February 2018 to December 2018 for comparison. Control subjects are selected such that they match the cases concerning certain characteristics, and perioperative data, voiding outcomes, and complications were evaluated at 1- and 12-month follow-up. The international prostatic symptomatic score (IPSS), quality of life (QoL), and maximum flow rate (Qmax) at 1 month and 12 months were both significantly improved compared with the preoperative baseline, and no significant differences were found between Groups A and B. The mean enucleation time, operation time, catheter indwelling duration, and hemoglobin decrease during the operation of Group A showed superiority compared with Group B (p<.05). The modified "fenestration and tunnel method" of HoLEP was statistically superior to the traditional trivalvular method in terms of the operation time, enucleation time, catheter indwelling duration, and hemoglobin decrease. For large-volume prostates (>80 ml), modified HoLEP was suggested to be a better treatment option.

Effect of electroacupuncture at Baihui ameliorated neurologic deficit and hemodynamic stability in rat model of post-cardiac arrest syndrome / 中华危重病急救医学

Objective:To observe the results of electroacupuncture (EA) on the resuscitation of a rat model of asphyxia cardiac arrest (CA). And to explore its effect on the neurologic deficits and hemodynamic instability of post-cardiac arrest syndrome (PCAS).Methods:A total of 107 male SD rats were randomly divided into sham, CA, and EA groups. Each group received arterial catheterization and tracheal intubation. The sham group was not induced asphyxia. Asphyxial cardiac arrest was established by endotracheal tube clamping. Rats in the CA group received basic respiratory support and fluid resuscitation in return of spontaneous circulation (ROSC) and rats in the EA group received EA at Baihui based on the treatment of CA group after ROSC, with a dense-dispersed wave at frequencies of 4-20 Hz, while the current intensity was adjusted minimum to induce a twitch of the scalp, the course of treatment was 30 minutes. The baseline data, hemodynamics after ROSC, neurological deficit score (NDS), pathological changes of brain tissue, and levels of serum biomarker were recorded and compared among the three groups. The 72-hour survival of rats was analyzed by Kaplan-Meier survival curve. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of necrotic neurons in the hippocampal CA1 region of rat brain. Meanwhile, Nissl staining and TdT-mediated dUTP nick-end labeling (TUNEL) were used to detect cell apoptosis and injury.Results:Compared with the CA group, the mean arterial pressure (MAP) in the EA group increased significantly at 15 minutes after ROSC [mmHg (1 mmHg≈0.133 kPa): 125.00 (94.00, 136.25) vs. 92.00 (72.00, 122.50), P < 0.05]. There was no significant difference in the NDS score between the EA group and the sham group. Still, the NDS score of the rats in the CA group at 6 hours after ROSC were significantly lower than that in the sham group (46.00±10.61 vs. 80.00±0.00, P < 0.05). Kaplan-Meier survival curve analysis showed that EA did not improve the 72-hour survival rate of rats (100% in the sham group, 25% in the CA group, and 30% in the EA group, P > 0.05). The analysis by TUNEL showed that the apoptosis rate of neurons in CA1 region of the hippocampus in EA group at 6 hours after ROSC was significantly lower than that in CA group [(62.84±2.67)% vs. (71.29±3.70)%, P < 0.05]. Compared with the CA group, the level of serum S100 calcium binding protein B (S100B) in the EA group at 6 hours after ROSC was significantly lower (ng/L: 19.30±13.87 vs. 132.28±31.67, P < 0.05), but there were no significant differences in the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) between these two groups. Conclusions:In the present study, EA at Baihui can stabilize the hemodynamic, moreover, it has a particular neuroprotective effect on PCAS rats. Still, EA at Baihui does not reduce the systemic inflammatory response and improve the survival rate of rats, and its mechanism remains to be verified in further research.

Effects of directional adaptation on selenium tolerance and accumulation of heterotrophic Chlorella pyrenoidosa / 生物工程学报

Selenium (Se) is an essential trace element for organisms. Se deficiency will cause diseases such as Keshan disease and Kashin-Beck in human being, and huge loss to animal husbandry. Currently available Se supplements have such problems as low Se content, poor bioavailability, and poor safety. Chlorella pyrenoidosa can produce bioavailable and safe organic Se under suitable conditions, which is thus a promising Se supplement. Therefore, in this study, we tried to improve the Se tolerance and accumulation of C. pyrenoidosa by directional adaptation. To be specific, we gradually increased the concentration of Na2SeO3 in medium to domesticate C. pyrenoidosa and optimized the adapting time and concentration gradient of Na2SeO3 during the adaptation. The results showed that the adapted C. pyrenoidosa was more tolerant to Se and had stronger Se enrichment ability. In 5 L fermenter, the adapted strains could tolerate 40 mg/L Na2SeO3 and the synthesis rate of organic Se was 175.6% higher. Then, Se addition method in the 5 L fermenter was optimized. The result demonstrated that addition of Na2SeO3 at 40 mg/L during heterotrophic culture achieved the final dry weight of C. pyrenoidosa cells at 106.4 g/L, content of organic Se at 1 227 mg/kg, and synthesis rate of organic Se at 1.36 mg/(L·h). Compared with the reported highest cell density of 75 g/L and the highest organic Se content of 560 mg/kg, the corresponding figures in this study were 41.9% and 119.1% higher, respectively. In conclusion, directional adaptation can remarkably improve the Se tolerance and enrichment of C. pyrenoidosa.

A network pharmacology approach to investigate the anticancer mechanism of cinobufagin against hepatocellular carcinoma via downregulation of EGFR-CDK2 signaling.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers with high mortality and poor prognosis, and the investigation on new approaches and effective drugs for HCC therapy is of great significance. In our study, we demonstrate that treatment with cinobufagin, a natural compound isolated from traditional chinese medicine Chansu, reduces proliferation and the colony formation capacity of the human hepatoma cells in vitro, in addition, cinobufagin induces mitotic arrest in human hepatoma cells. The results of a network pharmacology-based analysis show that EGFR, MAPK1, PTK2, CDK2, MAPK3, ESR1, CDK1, PRKCA, AR, and CSNK2A1 are the key targets involved in the anti-tumor activities of cinobufagin, additionally, several signaling pathways such as proteoglycans in cancer, pathways in cancer, HIF-1 signaling pathway, VEGF signaling pathway, ErbB signaling pathway, and PI3K-AKT signaling pathway are identified as the potential pathways involved in the inhibitory effects of cinobufagin against HCC. Furthermore, at the molecular level, we find that cinobufagin decreases EGFR expression and CDK2 activity in human hepatoma cells. Inhibition of EGFR or CDK2 expression could not only suppress the growth of tumor cells but also enhance the inhibitory effects of cinobufagin on the proliferative potential of human hepatoma cells. We also demonstrate that EGFR positively regulates CDK2 expression. Furthermore, EGFR inhibitor gefitinib or CDK2 inhibitor CVT-313 synergistically enhances anticancer effects of cinobufagin in human hepatoma cells. Taken together, these findings indicate that cinobufagin may exert antitumor effects by suppressing EGFR-CDK2 signaling, and our study suggests that cinobufagin may be a novel, promising anticancer agent for the treatment of HCC.

Gestational diabetes mellitus decreased umbilical cord blood polyunsaturated fatty acids: a meta-analysis of observational studies.

BACKGROUND: Polyunsaturated fatty acid (PUFA) is important for the development of the fetal brain, and the retina. Gestational diabetes mellitus (GDM) may influence maternal and fetal fatty acid metabolism, in turn affecting fetal growth and development. In several studies, maternal and fetal PUFA metabolic differences have been reported between mothers with and without GDM, but not in other studies. Thus, the aim of this meta-analysis (registration number: CRD42020220448) was to compare levels of linoleic acid (LA), α-linolenic acid (ALA), arachidonic acid (AA), docosahexaenoic acid (DHA), and total n-3 and n-6 PUFA between mothers with and without GMD and their fetuses. METHODS: We performed a meta-analysis of observational studies on maternal and fetal fatty acid metabolism, published until May 2021. In addition, we performed subgroup analysis depending on the analyzed tissues (plasma/serum, erythrocyte membrane, or placenta) and the expression modes of fatty acids (concentration or percentage). RESULTS: We included 24 observational studies involving 4335 maternal datasets and 12 studies involving 1675 fetal datasets in the meta-analysis. Levels of AA, DHA, and n-6 and n-3 PUFA were lower in the cord blood of mothers with GDM than in controls (P  <  0.05). Compared to that in controls, in erythrocyte membranes, the percentages of AA, DHA, and n-6 and n-3 PUFA in total fatty acid were lower in mothers with GDM (P  <  0.05), but in plasma/serum, the percentages of AA, DHA, and n-6 PUFA in total fatty acid were higher in mothers with GDM (P  <  0.05). CONCLUSIONS: GDM appears to influence the transfer of PUFAs from mothers to fetuses. The percentage of PUFAs in maternal plasma/serum was higher, and that in erythrocyte membranes was lower in mothers with GDM compared to those with normal glucose tolerance.

[Research progress on active components and mechanism of Isatidis Radix for influenza virus].

Isatidis Radix is the dried root of the Isatis indigotica, with pharmacological effects such as heat-clearing and detoxification, cooling blood and pharyngeal relief, antibacterial and anti-inflammatory effects. It is often used clinically to prevent and treat influenza and other diseases. In this paper, relevant domestic and foreign literatures in recent years were summarized, and it was found that Isatidis Radix lignans, indole alkaloids, polysaccharides, etc. were the main active components against influenza virus. Then its pharmacological effects and the mechanism of action were reviewed, providing a basis for in-depth research on the antiviral effect of Isatidis Radix.

3D Printed Bioceramic Scaffolds as a Universal Therapeutic Platform for Synergistic Therapy of Osteosarcoma.

The postoperative tumor recurrence and chemotherapy resistance in clinical osteosarcoma treatment have raised an imperative need to develop local implants for selectively killing residual tumor cells and simultaneously provide a scaffold for effectively filling the tumor resection-induced bone defects. Herein, a multifunctional platform is developed through successively coating TiN microparticles and doxorubicin (DOX) on the surface of tricalcium phosphate (TCP) scaffolds to achieve synergetic effects of photothermal therapy and chemotherapy for osteosarcoma. The content of TiN and DOX in the scaffolds can be flexibly adjusted by immersing the scaffolds into the solution containing different concentrations of TiN and DOX. The excellent therapeutic effect was achieved both in vitro and in vivo through the precise photothermal therapy and localized controlled-release chemotherapy. Moreover, the overall bulk scaffolds provide the mechanical support for bone tissue when implanting scaffolds into bone defects resulting from surgical removal of osteosarcoma. Importantly, using the poly(d,l-lactide) (PDLLA) as the medium, the scaffolds can be exploited as a universal platform for loading different kinds of therapeutic agents. This study may provide insights into designing multifunctional local implantation for eradicating tumors after surgical interventions with mitigated side effects.

The prognostic relevance of p53 and Ki-67 to chemotherapy sensitivity and prognosis in triple-negative breast cancer.

BACKGROUND: This study aimed to explore the prognostic function of p53 and Ki-67 protein expression in chemotherapy sensitivity and prognosis in triple-negative breast cancer (TNBC). METHODS: Patients who were confirmed with TNBC in Wenzhou Geriatric Hospital and Wenzhou Hospital of Traditional Chinese Medicine (including the Oncology Department, Tumor Surgery Department, and Gynecology Department) between January 2006 and February 2018 were included in this study. The expression of p53 and Ki-67 detected by immunohistochemistry, the rate of recurrence, and the objective curative effect evaluation at the end of the first-line rescue treatment were recorded for all patients. RESULTS: The patients were followed up to August 2020, and the median follow-up time was 9 years and 4 months. A total of 285 patients with TNBC were enrolled in the study. The patients ranged in age from 19 to 76 years old, with an average age of 53 years. The overall recurrence rate among the patients was 31.58%. The majority of cases (68.07%) were pathological stage I. The overall positive expression rates of Ki-67 and p53 were 53.33% and 56.84%, respectively. In the TNBC recurrence group, the positive rates of p53 and Ki-67 were 71.11% and 82.22%, respectively, which were significantly higher than those in the non-recurrence group. The positive rates of p53 and Ki-67 in the chemosensitive group were 96.05% and 92.11%, respectively, which were significantly higher than those in the non-chemosensitive group. Among all the TNBC patients, 128 patients had positive expression of both p53 and Ki-67, and 101 patients had negative expression of both p53 and Ki-67. The chemosensitivity rate of TNBC patients with positive expression of both Ki-67 and p53 was 98.53%, and that of TNBC patients with negative expression of both Ki-67 and p53 was 0.00%. The difference was statistically significant. The recurrence rate in TNBC patients with positive expression of both Ki-67 and p53 was 53.13%, and that in patients with negative expression of both Ki-67 and p53 was 6.93%. The difference was statistically significant. CONCLUSIONS: The expression of p53 and Ki-67 had prognostic relevance to chemotherapy sensitivity and prognosis in TNBC patients.

Research progress on natural cannabinoid receptor type 2( CB2R)regulators and their effects on bone metabolism / 中国中药杂志

Cannabinoid receptor type 2( CB2 R),a member of the G protein-coupled receptor( GPCR) superfamily,has a variety of biological activities,such as regulating pain response,resisting inflammation and fibrosis,and mediating bone metabolism. Some CB2 R regulators exhibit a good regulatory effect on bone metabolism. Cannabinoids in Cannabis sativa can cause psychoactive effects despite various pharmacological actions they exerted by targeting CB2 R. Therefore,it is of great significance to discover CB2 R regulators in non-Cannabis plants for finding new lead compounds without psychoactive effects and elucidating the action mechanism of plant drugs. The present study clarifies the discovery,structure,and physiological functions of CB2 R,especially its regulatory effects on bone metabolism,summarized CB2 R regulators extracted from non-Cannabis plants,and systematically analyzes the regulatory effects of CB2 R regulators on bone metabolism in animals,osteoblasts,and osteoclasts,to provide a scientific basis for the discovery of new CB2 R regulators and the development of anti-osteoporotic drugs.