Currently, the drug delivery system (DDS) based on nanomaterials has become a hot interdisciplinary research topic. One of the core issues is drug loading and controlled release, in which the key lever is carriers. Vaterite, as an inorganic porous nano-material, is one metastable structure of calcium carbonate, full of micro or nano porous. Recently, vaterite has attracted more and more attention, due to its significant advantages, such as rich resources, easy preparations, low cost, simple loading procedures, good biocompatibility and many other good points. Vaterite, gained from suitable preparation strategies, can not only possess the good drug carrying performance, like high loading capacity and stable loading efficiency, but also improve the drug release ability, showing the better drug delivery effects, such as targeting release, pH sensitive release, photothermal controlled release, magnetic assistant release, optothermal controlled release. At the same time, the vaterite carriers, with good safety itself, can protect proteins, enzymes, or other drugs from degradation or inactivation, help imaging or visualization with loading fluorescent drugs in vitro and in vivo, and play synergistic effects with other therapy approaches, like photodynamic therapy, sonodynamic therapy, and thermochemotherapy. Latterly, some renewed reports in drug loading and controlled release have led to their widespread applications in diverse fields, from cell level to clinical studies. This review introduces the basic characteristics of vaterite and briefly summarizes its research history, followed by synthesis strategies. We subsequently highlight recent developments in drug loading and controlled release, with an emphasis on the advantages, quantity capacity, and comparations. Furthermore, new opportunities for using vaterite in cell level and animal level are detailed. Finally, the possible problems and development trends are discussed.

Objective:To investigate how gut microbiota changes during prostate cancer radiotherapy and decipher the relationship of gut microbiota with disease progression and chronic radiation enteritis.Methods:Thirty-one patients with prostate cancer were included in this study,admitted to The First Affiliated Hospital of Xinjiang Medical University from September 2022 to December 2023.The clinical data and stool samples of the patients were collected,and patients were followed up.The collected stool specimens were subjected to 16S rRNA se-quencing to detect gut microbiota and bioinformatics analysis.Results:The relative abundance of phyla such as Firmicutes and Actinobac-teria increased,and that of Bacteroidetes decreased(P<0.05)with an increasing radiotherapeutic dose,while beta diversity was significantly higher(P=0.001).The relative abundance of the phylum Actinobacteria was significantly higher in the prostate cancer progression group than in the non-progression group(P<0.05),the relative abundances of genera such as Sutterella and Haemophilus were significantly higher in the progression group(P<0.05).That of Verrucomicrobia and its offshoots in Akkermansia was higher in the chronic radiation enteritis than in the non-enteritis group(P<0.05),while the relative abundances of Coprococcus_1 and Catabacter in the non-enteritis group were higher than those in the enteritis group(P<0.05).Conclusions:Radiotherapy dose accumulation significantly remodeled the floral structure.Sutterella and Haemophilus of the phylum Proteobacteria might be key flora in prostate cancer recurring early after treatment.An augmen-ted abundance of Akkermansia might increase the risk of chronic radiation enteritis,whereas the flora under the Lachnospiraceae branch might exert aprotective effect against chronic radiation enteritis.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

Objective:To investigate how gut microbiota changes during prostate cancer radiotherapy and decipher the relationship of gut microbiota with disease progression and chronic radiation enteritis.Methods:Thirty-one patients with prostate cancer were included in this study,admitted to The First Affiliated Hospital of Xinjiang Medical University from September 2022 to December 2023.The clinical data and stool samples of the patients were collected,and patients were followed up.The collected stool specimens were subjected to 16S rRNA se-quencing to detect gut microbiota and bioinformatics analysis.Results:The relative abundance of phyla such as Firmicutes and Actinobac-teria increased,and that of Bacteroidetes decreased(P<0.05)with an increasing radiotherapeutic dose,while beta diversity was significantly higher(P=0.001).The relative abundance of the phylum Actinobacteria was significantly higher in the prostate cancer progression group than in the non-progression group(P<0.05),the relative abundances of genera such as Sutterella and Haemophilus were significantly higher in the progression group(P<0.05).That of Verrucomicrobia and its offshoots in Akkermansia was higher in the chronic radiation enteritis than in the non-enteritis group(P<0.05),while the relative abundances of Coprococcus_1 and Catabacter in the non-enteritis group were higher than those in the enteritis group(P<0.05).Conclusions:Radiotherapy dose accumulation significantly remodeled the floral structure.Sutterella and Haemophilus of the phylum Proteobacteria might be key flora in prostate cancer recurring early after treatment.An augmen-ted abundance of Akkermansia might increase the risk of chronic radiation enteritis,whereas the flora under the Lachnospiraceae branch might exert aprotective effect against chronic radiation enteritis.

Objective To observe the value of dual-energy CT(DECT)for diagnosing knee gouty arthritis(GA)complicated with knee osteoarthritis(KOA).Methods Forty-eight cases of GA(GA group),30 cases of KOA(KOA group)and 60 cases of GA complicated with KOA(GA+KOA group)were retrospectively enrolled.Clinical and imaging data were compared among 3 groups and between each 2 groups,and the efficacy of DECT for diagnosing knee GA complicated with KOA was analyzed.Results Significant differences of detection rate and CT value of bone marrow edema(BME)were found among 3 groups and between each 2 groups(all P＜0.05),also of the course of disease,serum uric acid(SUA),monosodium urate(MSU)volume,bone erosion score and CT value between GA group and GA+KOA group(all P＜0.05).The area under the curve(AUC)of bone erosion score and CT value for diagnosing knee GA complicated with KOA was 0.779 and 0.824,respectively,and of the combination of the above 5 indexes was 0.898,higher than that of each parameter alone(all P＜0.05).Conclusion DECT was helpful for diagnosing knee GA complicated with KOA,and further combining with clinical parameters could improve its diagnostic efficacy.

Objective The purpose of the study is to breed homozygous interferon-γ knockout(IFN-γ-/-)mice and optimize the breeding strategies to achieve continuous and stable reproduction of IFN-γ-/-mice,which could be used as an ideal animal model for fundamental research.Methods Initially,heterozygous IFN-γ knockout(IFN-γ+/-)C57BL/6J mice were used as the parental generation for breeding.Subsequently,3 breeding strategies were employed using the offspring:(1)female heterozygotes mated with male heterozygotes;(2)male homozygotes mated with female heterozygotes;(3)female homozygotes mated with male homozygotes.The number and survival rate of IFN-γ-/-mice were compared across the three breeding strategies to determine the optimal breeding strategy.Under the optimal strategy,the effects of female mating age and diet type on the reproductive performance of IFN-γ-/-mice were further evaluated.Data from the first three litters of 60 IFN-γ-/-female mice,including litter size,number of weaning survivors,and weaning survival rate,were recorded and analyzed.In addition,the effects of dietary supplementation of pregnant mice and environmental optimization measures,such as the provision of shelters,were evaluated.Results Under conditions where the nutritional needs of pregnant mice were adequately met by supplementation with egg yolk and sunflower seeds,mating of female and male IFN-γ-/-mice result ed in a litter size of five to eight IFN-γ-/-mice,demonstrating higher efficiency compared to other breeding strategies.In addition,diet type and mating age significantly influenced female reproductive performance.When 7～9 weeks old female IFN-γ-/-mice were mated to male IFN-γ-/-mice and fed a high-protein breeding diet,litter size(6.9±1.7),weaning survival number(6.5％±2.0％)and weaning survival rate(93.2％±17.8％)were higher than those under other conditions.In addition,providing shelters to prevent fighting between breeding pairs further improved reproductive outcomes.Conclusions By adopting an optimized breeding strategy,combined with a high-protein diet,nutritional supplementation,and standardized mating age management,the breeding efficiency and stability of IFN-γ-/-mice can be significantly improved.This provides a reliable animal model for related research.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Methodological quality assessment is a pivotal link between primary studies and reliable evidence-based practice,and an essential pathway for operationalizing the core principles of the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition).A prevalent challenge in practice,however,is the conflation of appraising methodological robustness(risk of bias assessment)with verifying reporting transparency(adherence to reporting guidelines).This paper systematically addresses this fundamental challenge,beginning with a clear distinction between the essence and boundaries of these two concepts.On this basis,the article provides a comprehensive review of mainstream quality assessment tools,covering the methodological features and evolutionary trajectory of numerous instruments for interventional(e.g.,RoB 2,ROBINS-I),observational(e.g.,NOS,the JBI/SIGN/NIH series),secondary(e.g.,AMSTAR 2),and other specific types of studies such as health economic evaluations.Furthermore,a complete case study is used to illustrate the practical application of the ROBINS-I tool.The paper's central thesis advocates for an"appraisal-informed design"philosophy,urging a conceptual shift from the retrospective critique of existing literature to the prospective quality control of new research by internalizing appraisal standards as design principles,while also exploring the emerging paradigm of artificial intelligence in assisting assessment.This paper provides a comprehensive methodological reference for researchers and practitioners to prudently select appropriate assessment tools and to conduct rigorous critical appraisals of pharmacoepidemiological evidence.

Aim To evaluate the bioequivalence of two oral preparations of rivaroxaban tablets(test preparation T and refe-rence preparation R)in fasting/postprandibular state in healthy Chinese subjects.Methods A randomized,open,single-dose,four-cycle,completely repeated crossover experiment was used in this study.A total of 70 healthy male and female subjects were enrolled,including 38 subjects in the fasting group and 32 sub-jects in the postprandial group.Rivaroxaban tablets(2.5 mg/tablet)were taken orally once per cycle and their reference preparations were tested.The plasma rivaroxaban concentration was determined by LC-MS/MS method.The pharmacokinetic parameters of rivaroxaban tablets were calculated by WinNonlin software,and the parameters were analyzed and processed.Re-sults The PK parameters of rivaroxaban tablets and reference preparations in fasting group were as follows:Cmax was(72.48±17.08)and(66.36±15.64)μg·L-1,respectively.AUC0-t were(383.49±101.06)and(370.43±102.16)h·ng·mL-1,and AUC0-inr were(389.58±102.28)and(375.84±103.01)h·μg·L-,respectively.Main PK parameters of subjects taking rivaroxaban tablets orally after meals:Cmax were(66.48±15.64 and 60.87±13.44)μg·L-1,AUC0-t were(404.44±72.58)and(381.80±79.93)h·μg·L-1,re-spectively.AUC0_inf was(410.88±73.55)and(393.64±69.71)h·μg·L-1,respectively.Under fasting and postmeal conditions,subjects took rivaroxaban test and reference prepara-tion orally,one tablet(2.5 mg/tablet)each time.The geometric mean of the main pharmacokinetic parameters of rivaroxaban in plasma(Cmax,AUC0-t,AUC0-inf)and their corresponding values had a 90％confidence interval ranging from 80.00％to 125.00％.No serious adverse events or unexpected adverse e-vents occurred in both groups.Conclusion Rivaroxaban tablets are bioequivalent and safe in vivo under fasting and postprandial conditions.

Objective To investigate the incidence and types of patient-ventilator asynchrony(PVA)in mechanically ventilated patients within the intensive care unit(ICU),and to identify associated high-risk factors,thereby providing a basis for reducing PVA,enhancing mechanical ventilation efficiency,and refining ventilation strategies.Methods A prospective observational study was conducted among patients admitted to the general ICU of the Affiliated Hospital of Guizhou Medical University from October to December 2024 who were receiving mechanical ventilation.Inclusion criteria were as follows:age ≥18 years and mechanical ventilation duration ≥12 hours.Exclusion criteria included complete controlled mechanical ventilation,palliative care or do-not-resuscitate status,and lack of informed consent.Senior respiratory therapists performed daily bedside observations of ventilator waveforms for 10～15 minutes between 08:00 and 12:00.PVA was diagnosed based on pressure-time and flow-time waveforms,with the types of PVA being recorded.Demographic and clinical data,including age,sex,body mass index(BMI),primary diagnosis,comorbidities,APACHEⅡ score at ICU admission,blood gas analysis,ventila-tion mode and parameters,analgesia and sedation status,duration of mechanical ventilation,and length of ICU stay,were collected.The incidence and types of PVA during the observation period were analyzed.Univariate and multivariate logistic regression analyses were performed to identify high-risk factors for PVA.Clinical outcomes were compared between patients with and without PVA.Results A total of 105 patients and 453 episodes of assisted mechanical ventilation waveforms were analyzed.Among these,60.95％(64/105)experienced at least one episode of PVA.Of the 453 ventilation waveforms assessed,35.76％(162/453)demonstrated PVA.The types of PVA,ranked by incidence,were as follows:cycling mismatch(12.58％,57/453),double triggering(11.92％,54/453),ineffective triggering(9.49％,43/453),flow starvation(5.30％,24/453),and exhalation flow limitation(1.77％,8/453).The incidence of PVA varied significantly across different ventilation modes:45.7％in volume-assist/control ventilation(V-A/C),38.1％in pressure-assist/control ventilation(P-A/C),42.9％in synchronized intermittent mandatory ventilation(SIMV),and 16.7％in pressure support ventilation(PSV)(P<0.001).Multi-variate logistic regression analysis revealed that the mechanical ventilation mode[reference:PSV;V-A/C:OR=4.687,95％CI:2.140～10.263,P<0.001;P-A/C:OR=2.922,95％CI:1.489～5.734,P=0.002;SIMV:OR=4.682,95％CI:1.758～12.466,P=0.002]and actual respiratory rate(OR=1.07,95％CI:1.016～1.127,P=0.011)were significant high-risk factors for PVA.Patients with PVA had a significantly longer duration of mechanical ventilation[8.21(5.35,13.91)days vs.3.00(1.96,5.71)days,P<0.001]compared to those without PVA.Conclusions PVA is commonly observed in ICU patients receiving assisted invasive mechanical ventilation,with cycling mismatch,double triggering,and ineffective triggering being the most prevalent types.The incidence of PVA tends to be lower when using the PSV mode.Clinically,real-time monitoring of patient-ventilator synchrony via ventilator waveforms,along with the optimization of ventilator modes and parameters,should be employed to minimize the occurrence of PVA and enhance the efficiency of mechanical ventilation.