Pomegranate Juice Supplemented with Inulin Modulates Gut Microbiota and Promotes the Production of Microbiota-Associated Metabolites in Overweight/Obese Individuals: A Randomized, Double-Blind, Placebo-Controlled Trial.

Pomegranate juice (PJ) and inulin have been reported to ameliorate diet-induced metabolic disorders by regulating gut microbiota dysbiosis. However, there was a lack of clinical evidence for the combined effects of PJ and inulin on regulating gut microbiota in individuals with metabolic disorders. A double-blind, parallel, randomized, placebo-controlled trial was conducted, and 68 overweight/obese individuals (25 ≤ BMI ≤ 35 kg/m2) were randomly assigned to receive 200 mL/d PJ, PJ supplemented with inulin, or placebo for 3 weeks. Our results showed that PJ and PJ+inulin did not significantly alter the levels of anthropometric and blood biochemical indicators after 3 weeks of treatment. However, there was an increasingly significant impact from placebo to PJ to PJ+inulin on the composition of gut microbiota. Detailed bacterial abundance analysis further showed that PJ+inulin treatment more profoundly resulted in significant changes in the abundance of gut microbiota at each taxonomic level than PJ. Moreover, PJ+inulin treatment also promoted the production of microbiota-associated short-chain fatty acids and pomegranate polyphenol metabolites, which correlated with the abundance of the bacterial genus. Our results suggested that PJ supplemented with inulin modulates gut microbiota composition and thus promotes the production of microbiota-associated metabolites that exert potential beneficial effects in overweight/obese subjects.

Facile fabrication of temperature/pH dual sensitive hydrogels based on cellulose and polysuccinimide through aqueous amino-succinimide reaction.

A temperature/pH dual sensitive hydrogel with a semi-interpenetrating network (semi-IPN) structure was synthesized through an aqueous amino-succinimide reaction between water-soluble polysuccinimide and polyethyleneimine in the presence of thermosensitive cellulose derivatives. Single-factor experiments were carried out to optimize the preparation conditions of the semi-IPN hydrogel. The swelling behavior and cytotoxicity assay of the hydrogel were tested. Finally, taking 5- fluorouracil (5-Fu) as a model drug, the release performance of the 5-Fu-loaded hydrogel was investigated. The results indicated that the swelling ratio (SR) first decreased and then increased when the pH of the solutions ascended from 2 to 10. The SR decreased with the increase in temperature. In addition, the swelling behavior of the hydrogel was reversible and reproducible under different pH values and temperatures. The prepared hydrogels had good cytocompatibility. The release behavior of 5-Fu was most consistent with the Korsmeyer-Peppas model and followed the case II diffusion. The acidic environment was beneficial for the release of 5-Fu. The preparation process of the semi-IPN hydrogel is simple and the reaction can proceed quickly in water. The strategy introduced here has great potential for application in the preparation of drug carriers.

A historical controlled study of domestic trastuzumab and pertuzumab in combination with docetaxel for the neoadjuvant treatment of early HER2-positive breast cancer.

Background: HER2-positive molecular breast cancer subtypes are characterized by high aggressiveness and malignancy, and their metastasis and mortality rates are among the highest of all types of breast cancer. The use of anti-HER2-targeted agents in neoadjuvant therapy has significantly improved the prognosis of patients with HER2-positive breast cancer. In this study, we investigated the efficacy and safety of a neoadjuvant Chinese THP regimen (docetaxel, trastuzumab biosimilar TQB211 plus the pertuzumab biosimilar TQB2440 or pertuzumab) for ER/PR-negative and HER2-positive breast cancer in China. Method: All enrolled patients received the THP regimen (T: docetaxel 75 mg/m2 per cycle; H: trastuzumab biosimilar TQB211 8 mg/kg in the first cycle and 6 mg/kg maintenance dose in cycles 2 to 4; P: pertuzumab biosimilar TQB2440 or pertuzumab 840 mg in the first cycle, maintenance dose 420 mg in cycles 2 to 4) every 3 weeks for 4 cycles. The biosimilar TQB2440 pertuzumab and pertuzumab were randomly assigned to patients. Docetaxel, TQB211, and TQB2440 were all developed by Chiatai Tianqing. The primary endpoint was the complete pathological response (pCR) in the breast, and the secondary endpoint was cardiac safety. Results: Of the 28 eligible patients, 19 (67.9%) achieved tpCR. The tpCR rate was higher than in the NeoSphere trial (pCR63.2%) and the PEONY study (tpCR52.5%). The adverse events that occurred most frequently were leukopenia and neutropenia, with incidence rates of 82.1% and 75.0%, respectively. Of these, grade 3 leukopenia and neutropenia occupied 46.4% and 35.7%. Other grade 3 or higher adverse events were bone marrow suppression (7.1%), lymphopenia (3.6%), and anemia (3.6%). There were no events of heart failure in patients and no patient died during the neoadjuvant phase. Conclusion: Domestic dual-target HP has a more satisfactory efficacy and safety in the neoadjuvant phase of treatment. Clinical trial registration: https://clinicaltrials.gov/study/NCT05985187, NCT05985187.

Preparation and application of the thermo-/pH-/ ion-sensitive semi-IPN hydrogel based on chitosan.

Chitosan based hydrogels with multiple stimulus responses have broad application prospects in many fields. Considering the advantages of semi interpenetrating network (IPN) technology and the special temperature and ion responsiveness of polymers containing zwitterionic groups, a semi-IPN hydrogel was prepared through in situ free radical polymerization of N,N-dimethyl acrylamide and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide with polyethylene glycol dimethacrylate as a crosslinker and carboxymethyl chitosan as filler. The gel mass fraction and swelling ratio were measured, and the preparation conditions were optimized. The result indicated that the hydrogel possessed a unique thermo-/pH-/ ion-sensitive behavior. The swelling ratio increased with the increase of temperature and ion concentration, and showed a decreasing trend with the increase in pH. In addition, the hydrogel was stable when the stimuli changed. Adsorption behavior of the hydrogel to Eosin Y (EY) was systematically investigated. The adsorption process can be described well by the pseudo-second-order kinetic model and Langmuir isotherm model, indicating that it was a chemical adsorption. The experiments indicated that the hydrogel exhibited good antifouling and reusability features. Therefore, the semi-IPN hydrogel with antifouling properties and thermo-/pH-/ion-sensitivity can be easily manufactured is expected to find applications in water treatment fields.

Facile fabrication of a broad-spectrum starch/poly(α-l-lysine) hydrogel adsorbent with thermal/pH-sensitive IPN structure through simultaneous dual-click strategy.

A thermal/pH-sensitive interpenetrating network (IPN) hydrogel was prepared facilely from starch and poly(α-l-lysine) through amino-anhydride and azide-alkyne double-click reactions in one pot. The synthesized polymers and hydrogels were systematically characterized using different analytical techniques such as Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), scanning electron microscope (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and rheometer. The preparation conditions of the IPN hydrogel were optimized via one-factor experiments. Experimental results indicated the IPN hydrogel possessed pH and temperature sensitivity. Effect of different parameters (pH, contact time, adsorbent dosage, initial concentration, ionic strength, and temperature) on adsorption behavior were investigated in monocomponent system with cationic methylene blue (MB) and anionic Eosin Y (EY) as model pollutants. The results indicated that the adsorption process of the IPN hydrogel for MB and EY followed pseudo-second-order kinetics. The adsorption data for MB and EY fitted well with the Langmuir isotherm model, indicating monolayer chemisorption. The good adsorption performance was due to various active functional groups (-COOH, -OH, -NH2, etc.) in the IPN hydrogel. The strategy described here opens up a new way for preparing IPN hydrogel. The as-prepared hydrogel exhibits potential application and bright prospects as an adsorbent in wastewater treatment.

Development and Validation of the Prediction Model of Sepsis in Patients After Percutaneous Nephrolithotomy and Sepsis Progresses to Septic Shock.

Background: To study the predictors of sepsis and the progression of sepsis to septic shock in patients after percutaneous nephrolithotomy (PCNL) and to establish and validate predictive models. Methods: The patients were assigned to either the development cohort or the validation cohort depending on their hospital. In the development cohort, univariate and multivariate logistic regression analyses were used to screen independent risk factors for sepsis after PCNL and sepsis progression to septic shock. Nomogram prediction models were established according to the related independent risk factors. Areas under the receiver operating characteristic curves, calibration plots, and decision curve analysis (DCA) were used to estimate the discrimination, calibration, and clinical usefulness of the prediction models, respectively. The two sets of models were further validated on the validation cohort. Results: In the development cohort, the risk factors for sepsis after PCNL were diabetes, urine nitrite, staghorn calculi, HU value, albumin-globulin ratio, and high-sensitivity C-reactive protein/albumin ratio. The pre- and postoperative white blood cell counts were risk factors for the progression of sepsis to septic shock. The area under the ROC curve value for predicting sepsis risk was 0.891 and that for predicting septic shock risk was 0.981 in the development cohort; in the validation cohort, these values were 0.893 and 0.996, respectively. In the development cohort, the calibration test p values in the sepsis and septic shock cohorts were 0.946 and 0.634, respectively; in the validation cohort, these values were 0.739 and 0.208, respectively. DCA of the model in the sepsis and septic shock cohorts showed threshold probabilities of 10%-90% in the development cohort; in the validation cohort, these values were 10%-90%. Conclusion: The individualized nomogram prediction models can help improve the early identification of patients who are at higher risk of developing sepsis after PCNL and the progression of sepsis to septic shock to avoid further damage.

COVID-induced 3 weeks' treatment delay may exacerbate breast cancer patient's psychological symptoms.

The delayed access to cancer treatment due to the outbreak of COVID-19 pandemic posed a unique challenge to breast cancer patients and caused a significant level of mental distress among them. In the current research, we examined the psychological impacts of COVID on a subpopulation of breast cancer patients from a hospital in Shaanxi province of China using Symptom Checklist-90-R (SCL-90-R). Participants were 195 breast cancer patients at the outpatient clinic of Xijing hospital, Xi'an, Shaanxi Province, China. We found that a treatment delay of more than 3 weeks may exacerbate breast cancer patients' psychological symptoms, such as somatization, obsessive-compulsive disorder, interpersonal sensitivity, depression, hostility, phobic anxiety, paranoid ideation, and psychoticism, whereas a short-term delay of less than 3 weeks is less likely to have a significant effect on one's mental well-being. Additionally, breast cancer survivors, especially those at more advance stages, tend to experience more elevated psychological symptoms with longer treatment delay, and whose treatments continues to be delayed reported stronger psychological symptoms than individuals whose treatment are resumed, regardless of treatment type.

A model for sepsis prediction after retrograde intrarenal surgery and the use of the preoperative/postoperative white blood cell ratio to predict progression from sepsis to septic shock.

OBJECTIVES: To study the predictors of sepsis and progression to septic shock after RIRS; to establish and validate predictive models accordingly. METHODS: In total, 1220 patients were included in the study during. Eight hundred forty-eight patients were assigned to the development cohort and 372 to the validation cohort according to medical record. Univariate and multivariate logistic regression analyses were used to screen independent risk factors for post-RIRS (Retrograde intrarenal surgery) sepsis and progression to septic shock. Nomogram prediction models were established according to the related independent risk factors. Areas under the receiver operating characteristic curves, calibration plots, and DCA (Decision curve analysis) were used to estimate the discrimination, calibration and clinical usefulness of the prediction model, respectively. RESULTS: In the development cohort, sepsis occurred in 59 patients, 16 of whom developed septic shock. Multivariate logistic regression analyses showed that the independent risk factors for sepsis after RIRS were preoperative D-J stent implantation, hydronephrosis > 6.25 HU (Hounsfield units), AGR (Albumin/globulin ratio) < 1.95, hs-CRP/Alb (High-sensitivity C-reactive protein/albumin ratio) > 0.060, operating time > 67.5 min, and urinary nitrite positivity. The preoperative/postoperative WBC ratio > 1.5 was an independent risk factor for progression from sepsis to septic shock. In the development cohort, the AUC (Area under curve) for predicting sepsis risk was 0.845, and the AUC for predicting septic shock risk was 0.896; in the validation cohort, the corresponding values were 0.896 and 0.974, respectively. In the development cohort, the calibration test P values in the sepsis and septic shock cohorts, respectively, were 0.921 and 0.817; in the validation cohort, these values were 0.882 and 0.859. DCA of the model in the sepsis and septic shock cohorts showed threshold probabilities of 10-90% in the development cohort and 10-50% and 10-20% in the validation cohort. CONCLUSION: These individualized nomogram prediction models can improve the early identification of patients at risk for developing sepsis after RIRS or progressing from sepsis to septic shock.

Sulfonated polybenzothiazole cathode materials for Na-ion batteries.

A new flexible aromatic polymer sulfonated polybenzothiazole (sPBT-SE) with sulphone and ether units is reported as an advanced cathode material for storing Na+, which delivers a high discharge capacity of 103 mA h g-1 after 350 cycles at 30 mA g-1.

Upregulation of microRNA-762 suppresses the expression of GIPC3 in systemic lupus erythematosus and neuropsychiatric systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE), especially neuropsychiatric SLE (NPSLE), is a complex systemic autoimmune disease, characterized by variable course and multiple organ dysfunction. Our study aimed to identify crucial microRNA (miRNAs) in SLE and NPSLE. METHODS: Totally 12 cases of serum specimens were collected from General Hospital of Ningxia Medical University (SLE = 4, NPSLE = 4, control = 4). After miRNA sequencing, differential expression analysis, miRNA target prediction, and miRNA-messenger RNA (mRNA) regulatory network construction were performed to identify the hub miRNAs. The expression of target gene was determined by quantitative reverse transcription-polymerase chain reaction and Western blot. RESULTS: There were 79 and 59 differentially expressed miRNAs (DEmiRNAs) in NPSLE versus Control, and SLE versus Control, respectively. Among 35 overlapped DEmiRNAs, 5 upregulated miRNAs' (hsa-miR-762, hsa-miR-4270, hsa-miR-3663-3p, hsa-miR-4778-5p, and hsa-miR-4516) target genes were supported by at least six databases. The miRNA-mRNA network indicated that core miRNA hsa-miR-762 regulated 1270 target genes. MiR-762 was significantly upregulated in SLE and NPSLE, and over expression of miR-762 significantly suppressed GIPC PDZ domain containing family member 3 (GIPC3) expression in SLE and NPSLE. CONCLUSIONS: Upregulation of hub miRNA miR-762 can suppress the expression of GIPC3 in both SLE and NPSLE samples, which is probably involved in the development of SLE and NPSLE. Meanwhile, along with the development from SLE to NPSLE, miR-762 exhibits higher expression.

Facile fabrication of semi-IPN hydrogel adsorbent based on quaternary cellulose via amino-anhydride click reaction in water.

Clean and safe water resources play a key role in environmental safety and human health. Recently, hydrogels have attracted extensive attention due to their non-toxicity, controllable performance, and high adsorption. Herein, a semi- interpenetrating network hydrogel (semi-IPN-Gel) adsorbent based on quaternary cellulose (QC) was prepared by the amino-anhydride click reaction between maleic anhydride copolymer and polyacrylamine hydrochloride (PAH), and its adsorption properties for Eosin Y were studied. First, a binary copolymer (PAM) of acrylamide and maleic anhydride was synthesized by free radical polymerization. Then, the PAM, QC and PAH were dissolved in water, and the pH of the solution was adjusted to alkaline. Semi-IPN-Gel was successfully prepared by fast anhydride-amino click reaction. The preparation conditions of hydrogels were optimized by single-factor experiments. Finally, taking Eosin Y as a model pollutant, the adsorption performance of Eosin Y was studied. The factors influencing the adsorption capacity of the absorbents such as initial concentration of the Eosin Y, temperature, the amount of absorbent, ionic strength and pH of the Eosin Y solutions were investigated. And adsorption data were analyzed via the kinetic model and the isothermal model, indicating that the adsorption process of the hydrogel is a single layer chemisorption process.

Preparation and characterization of starch-cellulose interpenetrating network hydrogels based on sequential Diels-Alder click reaction and photopolymerization.

Herein, starch-cellulose interpenetrating network (IPN) hydrogels were fabricated by sequential Diels-Alder click reaction and photopolymerization in water. Moreover, ß-cyclodextrin, a commonly used host molecule in supramolecular chemistry, was also introduced to improve the performance of the IPN hydrogel. Firstly, the starch-based dienes were synthesized by modifying starch with N-maleoyl-ß-alanine, and the cellulose-based dienophiles were obtained by the reaction of cellulose and furfurylamide succinate; Secondly, the as-synthesized starch-based dienes, cellulose-based dienophiles, polymerizable ß-cyclodextrin, crosslinker, and acrylamide were dissolved in water and obtained a transparent solution. The solution was maintained in a water bath of 50 °C for 3 h, forming the first network via catalyst-free click Diels-Alder reaction, subsequently, the second network was formed by photopolymerization. Their preparation conditions were optimized via one-factor experiments and their properties and structures were characterized. Finally, 5- fluorouracil (5-Fu) was used as a model drug to study the sustained release behavior of the drug-loaded hydrogels. Release profile was found to fit in Ritger-Peppas kinetic model and polymer relaxation and drug diffusion made a valuable contribution to drug release. Taking into account the virtues of easily controllable photopolymerization and catalyst-free Diels-Alder reaction, the strategy described here has a potential application in the preparation of IPN hydrogels.

Factors Associated With Surgical Modality Following Neoadjuvant Chemotherapy in Patients with Breast Cancer.

BACKGROUND: The breast-conserving surgery (BCS) rate for patients with breast cancer in China is much lower than that in Europe and the United States. This study aimed to identify factors affecting the choice of surgical modality following neoadjuvant chemotherapy (NAC) in patients with breast cancer in northwest China. PATIENTS AND METHODS: Patients who underwent mastectomy or BCS after NAC for invasive breast cancer from January 2013 to December 2017 were enrolled in the study. Single-factor and multivariate logistic regression analyses were applied to identify the association between the type of surgery and demographic characteristics or clinical pathological factors of patients. RESULTS: This study enrolled 916 patients. Among them, 191 patients (20.9%) and 725 patients (79.1%) underwent BCS and mastectomy, respectively. Patients with high education were less likely to undergo mastectomy compared with patients with less education (P < .001; odds ratio [OR] = 0.50; 95% confidence interval [CI], 0.35-0.71). Patients with cT3 tumors were nearly six times more likely to undergo mastectomy compared with patients with cT1 tumors (P = .003; OR = 5.74; 95% CI, 2.07-15.97). Moreover, patients older than 50 years of age (P < .001; OR = 2.84; 95% CI, = 1.93-4.16) were more likely to be offered mastectomy. No association between the type of surgery and pathological complete response (P = .351) was observed. CONCLUSION: Pretreatment clinical disease size remains a strong predictor of surgical management, whereas response to NAC appeared to play no role in the surgical decision, suggesting that the potential surgical benefits of NAC may be still under-recogonized in northwest China.

Synthesis and characterization of double-network hydrogels based on sodium alginate and halloysite for slow release fertilizers.

In this work, novel sodium alginate-based double-network hydrogel beads were prepared and applied for the water-retention and slow release of fertilizers (WSF). The WSF beads were prepared by ion-crosslinking and the free radical polymerization of acrylic acid, acrylamide, and polymerizable ß-cyclodextrin in the presence of urea-loaded halloysites. The WSF beads were characterized using SEM, FTIR, and TGA. Their swelling capacity and water retention were measured by a weighing method and their slow-release behavior was studied by spectrophotometry. The water retention and slow release results showed that the fertilizer displayed improved urea release and water retention properties, indicating that halloysite nanotubes clearly improved the performance of fertilizers. In addition, the experimental data of the slow release of urea in water and soil better fitted the Korsmeyer-Peppas model compared with the Higuchi model, a zero-order model or a first order mode. The release behavior of the fertilizer beads followed a Fickian diffusion mechanism.

Simultaneous Diels-Alder click reaction and starch hydrogel microsphere production via spray drying.

Herein, starch was used as a raw material to produce hydrogel microspheres via a strategy that combines spray drying and a Diels-Alder reaction. First, the starch was modified with N-maleoyl alanine and succinic acid amide. Second, starch hydrogel microspheres (SGPs) and drug-loaded hydrogel microspheres (5-Fu/SGPs) were produced by spray drying an aqueous solution of the as-prepared modified starch, forming chemical crosslinks via an in situ Diels-Alder reaction during the spray drying. The microspheres slowed the release rate of 5-Fu. In vitro cytotoxicity tests indicated that the SGPs are non-toxic for model human breast cancer cells; however, the 5-Fu/SGPs demonstrated clear cytotoxicity for human breast cancer cells. Taking into account the ease of the spray drying process and the good performance of the prepared microspheres, the strategy presented here has the potential to be applied to the green preparation of drug-loaded hydrogel microspheres.

Glucose ligand modififed thermally activated delayed fluorescence targeted nanoprobe for malignant cells imaging diagnosis.

Probes with long lifetime fluorescent emission are highly desirable for time-resolved fluorescence imaging to eliminate the interference from short-lived auto-fluorescence. Aromatic-imide-based thermally activated delayed fluorescence material TADF compound with high external quantum efficiency was encapsulated with Glucose-PEG2000-DSPE amphiphilic copolymer to prepare nanoprobe micelles. Glucose-PEG2000-DSPE TADF (GPDT) Micelles had good biocompatibility, biodegradability, less toxicity, and they could be efficiently transported by over expressed GLUT1 on tumor cell membrane, then efficiently targeted lysosome of HepG2 cells. GPDT Micelles had great clinical application and research development value, and be suitable for the application and popularization in fluorescence imaging technology, especially time-resolved fluorescent imaging in living cells.

Preparation of dummy molecularly imprinted polymers for extraction of Zearalenone in grain samples.

Surface molecularly imprinted polymers (MIL-101@MIPs) were prepared using MIL-101 as supporting core, imprinted polymers as selective shell synthesized with coumarin-3-carboxylic acid as dummy template of Zearalenone (ZEN), methacrylic acid as functional monomer, and ethylene glycol dimethacrylate hydroxyethyl methacrylate as cross-linker. The polymers were characterized by scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and particle-size distribution analyses. MIL-101@MIPs were used as the sorbent to compose the self-made cartridge. The cartridge was used to purify and enrich ZEN from real samples. Under optimized SPE conditions, a self-made cartridge can be reused for at least seven cycles. Elution was monitored with a high-performance liquid chromatography-fluorescence detection system. The linearity of the method ranged within 6.25-250 ng kg-1. The limits of detection ranged within 2.09 - 4.16 ng kg-1, and the limits of quantification ranged within 6.25 -12.50 ng kg-1, respectively. The matrix effects of four real samples were discussed. The spiking recoveries of ZEN ranged within 81.70%-90.10% with relative standard deviations lower than 5.56%. The performance of the self-made cartridge and immunoaffinity column was compared by chromatography.

A multifunctional self-healing G-PyB/KCl hydrogel: smart conductive, rapid room-temperature phase-selective gelation, and ultrasensitive detection of alpha-fetoprotein.

A multifunctional G-PyB/KCl hydrogel showed outstanding self-healability, high conductivity, and rapid room-temperature phase-selective gelation capacity, and was developed as an electrochemical aptamer sensing platform for the ultrasensitive detection of alpha-fetoprotein.

Preparation and characterization of slow-release and water-retention fertilizer based on starch and halloysite.

In this work, a kind of slow-release and water-retention fertilizer was fabricated by free radical copolymerization of potato starch, acrylic acid, acrylamide, and ß-cyclodextrin modified by maleic anhydride, accompanying halloysite nanotubes whose cavities were enlarged by acidification and loaded with urea in advance. The fertilizer was characterized by FTIR, TGA, SEM, TEM, and XRD. Its swelling behavior in distilled water and salt solutions as well as the ability to hold water was studied by weighing method. Finally, its controlled-release behavior to urea was investigated. The results suggested the as-prepared fertilizer had good abilities to retain water and control urea release. Moreover, the addition of halloysite helped to improve the release properties of the fertilizer. The study on urea release kinetics indicated the release behavior of urea in water was controlled by its concentration, whereas the release behavior of urea in soil fitted with Fickian diffusion mechanism.