Taxifolin (Tax) has been proved to be a medicinal edible substance with protective effects against alcoholic liver injury, however, its poor hydrophilicity and permeability have hindered the clinical application of Tax. In this study, we prepared taxifolin-phosphatidylcholine/sodium deoxycholate/PVP-K30 micells (Tax-MLs). Box-Behnken test was used to obtain the optimal preparation process, and Tax-MLs were characterised by transmission electron microscopy and fourier transform infrared spectroscopy. Physicochemical parameters such as proximate micelle concentration, equilibrium solubility and oil-water partition coefficient were determined, and the release pattern of Tax-MLs was investigated by in vitro digestion simulation. Alcoholic liver injury model to explore the in vivo efficacy of Tax-MLs. The results showed that the average particle size, polydispersity index (PDI) and zeta potential of Tax-MLs were 36.90 ± 4.57 nm, 0.194 ± 0.01 and -32.6 ± 0.35 mV, respectively, and the uniform size and distribution of Tax-MLs were observed by transmission electron microscopy. The formation of Tax-MLs was proved by differential scanning calorimetry and fourier transform infrared spectroscopy. In terms of physicochemical properties, the solubility of Tax-MLs in water increased by 92.02 times compared with Tax, and its oil-water partition coefficient in water increased from 0.43 to 1.14, which proved that Tax-MLs could improve its solubility and permeability. The in vivo pharmacodynamic results showed that compared with the Tax group, Tax-MLs low, medium and high dose groups showed a significant reduction in liver indices and serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < 0.05), and enhanced the activities of superoxide dismutase (SOD) and glutathione (GSH), and lowered the levels of malondialdehyde (MDA) more significantly in the hepatic tissues. Tax-MLs effectively improved drug solubility and permeability, and enhanced the protective effect against alcoholic liver injury. Animal experiments were conducted with approval from the Animal Ethics Committee of Changchun University of Traditional Chinese Medicine (approval number: 2023601).

[Objective] To establish a cryopreservation protocol for small-volume (≤1 mL) red blood cells (RBCs) and to evaluate the reactivity and stability of blood group antigens after cryopreservation, so as to explore its potential application in immunohematology reference laboratories. [Methods] Small-volume RBCs were cryopreserved for 120 days, followed by thawing and deglycerolization to restore the RBC components. The quality of the RBCs was assessed. Serum antibodies were serially diluted and reacted with RBCs before and after cryopreservation, and agglutination scores were recorded to quantitatively evaluate the reactivity and stability of blood group antigens such as Rh, Duffy, Lewis, Kidd, M, and H. Flow cytometry was used to analyze the percentage and mean fluorescence intensity of ABO antigen expression on RBCs before and after cryopreservation to assess the usability of cryopreserved RBCs in flow immunophenotyping and blood group subtype studies. [Results] The hemolysis rate of thawed and deglycerolized RBCs was (0.27±0.10)%, with a supernatant free hemoglobin level of (0.52±0.14) g/L, and the RBC recovery rate was (69.12±7.91)%. The direct antiglobulin test (DAT) was negative for all thawed RBCs. There was no difference in the reactivity of blood group antigens before and after cryopreservation, and no difference in the percentage and mean fluorescence intensity of A and B antigen expression on RBCs before and after cryopreservation. [Conclusion] The small-volume RBC cryopreservation protocol can be applied to immunohematology analysis in reference laboratories and is expected to be widely used in blood group identification, antibody screening, identification, and blood group-related research.

Objective: To analyze the association of sedentary types with symptom of depressive and anxiety among college freshmen, so as to provide a reference for improving the mental health of college students. Methods: From October to November 2022, all college freshmen at three colleges and universities in Anhui Province were selected by a cluster sampling method. The Generalized Anxiety Disorder-7 (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), and the Youth Leisure-Time Sedentary Behavior Questionnaire (YLSBQ) were used for the investigation. A binary Logistic regression analysis was conducted to investigate the relationship of different types of sedentary behavior with anxiety and depressive symptom. Results: The detection rates of anxiety and depressive symptom among college freshmen were 32.8% and 49.9%, respectively. The results of the binary Logistic regression model analysis showed that after controlling for gender, family location, parental education level, self rated family economic status and number of intimate partners, high level overall, video based, and social based sedentary time were associated with an increased risk of anxiety ( OR =1.26, 1.56, 1.27) and depressive symptom ( OR =1.42, 1.94, 1.29) among college freshmen; the association between moderate level sedentary time and depressive symptom was statistically significant ( OR =0.83) (all P <0.05). The overall trends of the association between sedentary behavior with symptom of anxiety and depressive were similar in both boys and girls. Conclusions Sedentary behavior is associated with an increased risk of anxiety and depressive symptom in college students. Reducing video based and social based sedentary behaviors is beneficial for mental health promotion in college students.

Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.

Peroxisome proliferator-activated receptor gamma(PPAR-γ)is a member of the ligand-activated nuclear tran-scription factor superfamily.Activated PPAR-γ is involved in the regulation of many central nervous system(CNS)events,and is involved in cholesterol metabolism by inducing or inhibi-ting a series of gene pathways,thereby inhibiting the deposition of β-amyloid protein(Aβ).It plays an important neuroprotec-tive role in Alzheimer's disease(AD),improves memory and cognition in AD,and is a potential target for AD.Drug develop-ment aimed at restoring cholesterol homeostasis may be a poten-tial strategy to counteract AD.By analyzing the distribution and structure of PPAR-γ,focusing on the biological correlation be-tween PPAR-γ-mediated cholesterol metabolism and AD,this paper describes the mechanism regulation of PPAR-γ on key proteins,genes and their corresponding molecules,providing a new reference for the treatment of AD.

Overexpression of P-glycoprotein(P-gp)is one of the major causes of therapeutic resistance to a variety of drugs,in-cluding antitumor drugs.P-gp has a wide range of substrates that are capable of expelling drugs from the cell via a twist-squeeze mechanism,leading to drug resistance.To address the problem of P-gp-mediated multidrug resistance,several inhibitors are being investigated.This article reviews the current small mole-cule compounds,natural source compounds and pharmaceutical excipients capable of inhibiting P-gp,and summarizes the cur-rent mechanisms of action of P-gp inhibitors,which are mainly competitive or non-competitive inhibition,stimulation of ATPase activity,down-regulation of expression,and metamorphic modu-lation.Currently,it is mainly the drug interactions and toxic re-actions that limit their clinical applications.

The aim of this study was to trace to origin of SARS-CoV-2 originating from imported cold-chain products re-sponsible for an outbreak that occurred on September 6-9,2022 in Mawei District,Fuzhou City,Fujian Province,China.Sam-ples from all positively infected persons and one positive sample from a swab of a cold-chain product during the outbreak were collected for gene sequencing.Epidemiological investigations were conducted on all positively infected persons to analyze the chain of transmission of the virus.Nucleic acids were detected by real-time fluorescence quantitative PCR,and the outbreak was characterized by a total of eight positive infections,which were asymptomatic.Whole-genome sequencing of three infected per-sons and one cold-chain product sample identified 75 nucleotides and 55 amino acid mutation sites of the BA.2.3.7 variant,with four highly homologous whole-genome sequences.These results confirmed that the outbreak was caused by exposure to impor-ted cold-chain products carrying the SARS-CoV-2 Omicron BA.2.3.7 strain.

Redox-sensitive cysteine(RSC)thiol plays an important role in many biological processes such as photosynthesis,cellular metabolism,and transcription.Therefore,it is necessary to identify red-ox-sensitive cysteine accurately.However,traditional redox-sensitive cysteine identification is very ex-pensive and time-consuming.At present,there is an urgent need for a mathematical calculation method to identify sequence information and redox-sensitive cysteines quickly and accurately.Here,we devel-oped an effective predictor called iRSC-PseAAC,which used the dimension reduction algorithm LDA combined with the support vector machine to predict redox-sensitive cysteine sites.In the cross-validation results,the specificity(Sp),sensitivity(Sn),accuracy(Acc)and Matthews correlation coefficient(MCC)were 0.841,0.868,0.859 and 0.692 respectively.In the independent dataset results,the Sp,Sn,Acc and MCC were 0.906,0.882,0.890 and 0.767 respectively.compared with existing prediction methods,iRSC-PseAAC had obvious improvement effect.The method proposed for this study can also be used for many problems in computational proteomics.

Objective:To investigate the clinical efficacy and safety of ixazomib-containing regimens in the treatment of patients with multiple myeloma(MM).Methods:A retrospective analysis was performed on the clinical efficacy and adverse reactions of 32 MM patients treated with a combined regimen containing ixazomib in the Hematology Department of the First People's Hospital of Lianyungang from January 2020 to February 2022.Among the 32 patients,15 patients were relapsed and refractory multiple myeloma(R/RMM)(R/RMM group),17 patients who responded to bortezomib induction therapy but converted to ixazomib-containing regimen due to adverse events(AE)or other reasons(conversion treatment group).The treatment included IPD regimen(ixazomib+pomalidomide+dexamethasone),IRD regimen(ixazomib+lenalidomide+dexamethasone),ICD regimen(ixazomib+cyclophosphamide+dexamethasone),ID regimen(ixazomib+dexamethasone).Results:Of 15 R/RMM patients,overall response rate(ORR)was 53.3％(8/15),among them,1 achieved complete response(CR),2 achieved very good partial response(VGPR)and 5 achieved partial response(PR).The ORR of the IPD,IRD,ICD and ID regimen group were 100％(3/3),42.9％(3/7),33.3％(1/3),50％(1/2),respectively,there was no statistically significant difference in ORR between four groups(x2=3.375,P=0.452).The ORR of patients was 50％after first-line therapy,42.9％after second line therapy,60％after third line therapy or more,with no statistically significant difference among them(x2=2.164,P=0.730).In conversion treatment group,ORR was 88.2％(15/17),among them,6 patients achieved CR,5 patients achieved VGPR and 4 patients achieved PR.There was no statistically significant difference in ORR between the IPD(100％,3/3),IRD(100％,6/6),ICD(100％,3/3)and ID(60％,3/5)regimen groups(x2=3.737,P=0.184).The median progression-free survival(PFS)time of R/RMM patients was 9 months(95％CI:6.6-11.4 months),the median overall survival(OS)time was 18 months(95％CI:11.8-24.4 months).The median PFS time of conversion treatment group was 15 months(95％CI:7.3-22.7 months),the median OS time not reached.A total of 10 patients suffered grade 3-4 adverse event(AE).The common hematological toxicities were leukocytopenia,anemia,thrombocytopenia.The common non-hematological toxicities were gastrointestinal symptoms(diarrhea,nausea and vomit),peripheral neuropathy,fatigue and infections.Grade 1-2 peripheral neurotoxicity occurred in 7 patients.Conclusion:The ixazomib-based chemotherapy regimens are safe and effective in R/RMM therapy,particularly for conversion patients who are effective for bortezomib therapy.The AE was manageable and safe.

Objective:To investigate the accuracy and feasibility of applying rapid immunohistochemistry(IHC) with CK5/6 antibodies in prostate biopsy tissues to assist frozen pathology diagnosis.Methods:The data of 41 patients who underwent prostate puncture and frozen tissue rapid IHC with CK5/6 antibody in Beijing Hospital from October 2022 to April 2023 were retrospectively analyzed. The median age of the patients was 76 (69, 79) years old, and the median PSA value was 12.37 (7.07, 26.17) ng/ml.The Prostate Imaging Reporting and Data System (PI-RADS) scores of the target lesions were all ≥3. The PI-RADS score of 9 patients(21.95%) was 3, 15 (36.59%) was 4, and 17(41.46%) was 5. The median diameter of the lesions in the MRI examination was 1.40 (1.09, 2.20) cm.Fourteen lesions (34.14%) were located in the migratory zone, 23 (56.10%) were located in the peripheral zone, and 4 (9.76%) involved both peripheral and migratory zone lesions. Transperineal cognitive fusion targeted combined systematic biopsy was used, and intraoperatively, 1 additional needle was taken from each of the target and non-target areas for frozen pathology section, and hematoxylin eosin(HE) staining and rapid IHC staining with CK5/6 antibody was performed, then the frozen remaining tissue was HE staining and CK5/6 IHC staining. Data such as HE and rapid IHC results of frozen pathology sections and HE and IHC results of routine sections of the frozen remaining tissues, International Society of Urological Pathology (ISUP) grading groupings(GG), and actual diagnostic results of targeted combined systematic puncture were recorded. Using the routine IHC results of the same needle tissue as the gold standard, the sensitivity and positive predictive value of applying rapid IHC frozen pathology to diagnose prostate cancer and the accuracy of its pathological GG were analyzed.Results:Among the 41 patients, a total of 35 cases were diagnosed with prostate cancer(PCa) by HE staining in frozen section of target tissue, with a positivity rate of 85.37%(35/41). Among these, there were 17 cases (48.57%) in ISUP GG 1, 8 cases (22.86%) in GG 2, 4 cases (11.43%) in GG 3, and 6 cases (17.14%) in GG 4 to 5. In addition, a total of 35 cases were diagnosed with PCa by HE staining in frozen remaining section of target tissue, with a positivity rate of 85.37%(35/41). Among these, there were 17 cases (48.57%) in ISUP GG 1, 8 cases (22.86%) in GG 2, 4 cases (11.43%) in GG 3, and 6 cases (17.14%) in GG 4 to 5. The results of rapid IHC of target tissue: 35 cases were negative for CK5/6 expression and 6 cases were positive. The results of routine IHC of target tissue: 35 cases were negative for CK5/6 expression and 6 cases were positive. The results of rapid IHC of non-target tissue: 12 cases were negative for CK5/6 expression and 29 cases were positive. The results of routine IHC of non-target tissue: 12 cases were negative for CK5/6 expression and 29 cases were positive. Thirty-five cases of target tissue rapid IHC diagnosis of PCa were in complete agreement with routine IHC diagnosis, with a false-positive rate of 0, a sensitivity of 100.00% (35/35) and a positive predictive value of 100.00% (35/35). Twelve cases of non-target tissue rapid IHC diagnosis of PCa were in complete agreement with routine IHC diagnosis, with a false-positive rate of 0, a sensitivity of 100.00% (35/35), and a positive predictive value of 100.00% (12/12).Conclusions:The preliminarily study results confirmed that the application of rapid IHC with CK5/6 antibodies in prostate biopsy tissues assisted frozen pathology diagnosis with high accuracy, but the reliability of rapid IHC technology in assisting frozen pathological diagnosis during puncture surgery still needs further validation through large sample size prospective studies.