AIM To prepare the soluble microneedles of Aconitum brachypodum Diels alkaloids.METHODS Centrifugal molding method was adopted in the preparation of soluble microneedles.With chondroitin sulfate consumption,PVP K120 consumption and 40%ethanol consumption as influencing factors,piercing rate as an evaluation index,the formulation was optimized by Box-Behnken response surface method,after which the morphology,piercing performance,drug content and in vitro transdermal performance were investigated.RESULTS The optimal formulation was determined to be 123 mg for chondroitin sulfate consumption,298 mg for PVP K120 consumption,and 2.4 mL for 40%ethanol consumption,the piercing rate was 98.3%.The soluble microneedles were yellow and square patch with conoid needle,which could pierce aluminum foil and rat skin,along with the drug content of(0.94±0.025)mg.The soluble microneedle group demonstrated the accumulative permeability rate of 91.4%within 24 h,which was higher than that in the gel ointment group,and the permeability accorded with Higuchi equation.CONCLUSION The soluble microneedles of A.brachypodum alkaloids exhibit good mechanical strength,which can achieve effective transdermal delivery of drugs.

The paper is to establish an UPLC-MS/MS method for the simultaneous determination of 19 components in Microctis Folium from different production areas. The 50% methanol was used as extraction solvent. The Agilent ZORBAX SB C18 (150 mm × 2.1 mm, 1.8 μm) column was used; mobile phase was acetonitrile - 0.1% acetic acid with gradient elution, flow rate was 0.3 mL·min^-1, colume temperature was 30 ℃, and the injection volume was 2 μL; electrospray ionizaton source was used and detected in negative ion mode. The results showed that the established UPLC-MS/MS method could well separate the 19 components, and the methodological investigation results of 19 components were good. By means of orthogonal partial least squares discriminant analysis (OPLS-DA), 28 batches of Microctis Folium samples from different production areas can be divided into three categories, Guangdong, Guangxi and Hainan are each classified into one category, and 10 signature compounds which affecting the quality differences of different production areas were screened out. The established method is accurate, reliable, sensitive and reproducible. It can provide a basis for the establishment of the quality standard of Microctis Folium, as well as for safety and quality research.

Objective:To evaluate the academic quality and influence of Chinese Journal of Epidemiology in recent years, the main citation indicators of Chinese Journal of Epidemiology from 2019 to 2022 were analyzed. Methods:The total citation frequency, impact factor and others, etc. of Chinese Journal of Epidemiology were extracted from " Chinese S & T Journal Citation Report ( Natural Edition)" and " Chinese S & T Journal Citation Report( Extended Edition)", clout index (CI) was extracted from the Annual Report for Chinese Academic Journal Impact Factors( Natural Science), and World Journal Clout Index (WJCI) and quartile information were extracted from World Journal Clout Index( WJCI) of Scientific and Technological Periodicals for the analyses on the academic quality and influence of Chinese Journal of Epidemiology in recent years. Results:The annual source literature volume of Chinese Journal of Epidemiology were 299, 290, 346 and 335 from 2019 to 2022, respectively. The literature selection rates were 94%, 95%, 88% and 94%, respectively. The total core citation frequency increased from 5 055 in 2019 to 6 390 in 2022, and the total expanded citation frequency increased from 7 817 in 2019 to 9 550 in 2022. The core impact factors increased from 1.842 in 2019 to 3.371 in 2022, showing an upward trend and reaching a new historical high level. The extended impact factor increased from 2.799 in 2019 to 4.806 in 2022. The CI of Chinese Journal of Epidemiology increased from 1 048.704 in 2019 to 1 352.725 in 2022. The WJCI values of Chinese Journal of Epidemiology were 2.193, 4.327, 3.015, and 2.446 from 2019 to 2022, respectively, which were in Q1 quartile from 2020 to 2022. Conclusions:The main citation indicators of Chinese Journal of Epidemiology showed upward trends from 2019 to 2022, with the impact factor reaching a new historical high level. Since the inclusion in the Excellent Action Plan of Chinese Science and Technology Journals in 2019, the academic quality of Chinese Journal of Epidemiology has been improved continuously, resulting in significant increase of its domestic and international influence.

Objective:To analyze the characteristics of highly-cited papers in Chinese Journal of Epidemiology from 2020 to 2023, and provide a basis for subsequent paper solicitation and identify research hotspots. Methods:On December 9, 2023, the citation frequency of each paper in Chinese Journal of Epidemiology from 2020 to 2023 was obtained from China National Knowledge Infrastructure. The total citation frequency of each paper was sorted using Excel 2016 software, and papers with citation frequency ≥30 were extracted for analysis. The keywords of the papers and Contents in Brief were analyzed. Results:A total of 1 317 papers were included in the analysis, of which 389, 342, 308 and 278 papers were included from 2020 to 2023. The total citation frequency was 11 873, and all papers were cited with an average citation frequency of 9. The keywords with high citation frequency in the papers included 2019-nCoV, hypertension, colorectal tumor, hand-foot-mouth disease, hepatitis B. and the average frequency of citation were 162, 77, 62, 51 and 47, respectively. There were 15 highly cited Contents in Brief in total, 11 of which are vital Contents in Brief or unique Contents in Brief, including Response to COVID-19 Epidemic, China Kadoorie Biobank, Epidemiological Research on Infectious Diseases, Healthy Ageing, Colorectal Cancer Prevention and Control, Prevention and Control of Hepatitis B, Quality Assessment of Cancer Screening Guidelines and Consensus, The 40 th Anniversary of Chinese Journal of Epidemiology, Expert Forum, Review, Standard-Protocol-Guide. The total citation frequency was 3 951, accounting for 72.6% (3 951/5 438) of highly cited papers. Conclusions:In the past four years, the highly cited papers of this journal mainly focused on the research field of emerging infectious diseases and chronic diseases. The response to the 2019-nCoV epidemic highlights the academic leading role. The effect of selecting and planning a topic, commissioning authors to write on given topics and making an arrangement in advance with a subject for contribution to vital Contents in Brief or unique Contents in Brief of this journal is pronounced, and the academic influence of the journal continues to improve.

Objective:To evaluate the regeneration and biomechanical property recovery of semitendinosus tendon(ST)/gracilis tendon(GT) after anterior cruciate ligament(ACL) reconstruction using shear wave elastorgraphy (SWE) combined with high-frequency ultrasound(HFUS).Methods:Twenty-five patients who underwent ST/GT autograft reconstruction after ACL rupture at the People′s Hospital of Guangxi Zhuang Autonomous Region from January 2020 to June 2022 were prospectively enrolled. All patients underwent HFUS, SWE and flexion strength assessment at pre-operation and 1, 3, 6, 12, 24 months postoperatively. The morphology, length, cross-sectional area and SWE of ST/GT and flexion strength of knee were recorded at each time point. Repeated measures analysis of variance was employed to compare the cross-sectional area and elasticity value of regenerated ST/GT at different time points. Spearman correlation analysis was used to investigate the relationship between the elasticity value of regenerated ST/GT and flexion strength.Results:The regeneration rates of ST/GT after being harvested for ACL reconstruction were 88% and 92%. The length of the regenerated ST/GT were shorter than before operation(both P<0.05). Repeated measures analysis of variance revealed significant differences in the cross-sectional area of regenerated ST/GT, both in terms of time effect and inter-group effect ( F=27.264, 28.980; both P<0.001), but no significant difference was observed in the interaction effect ( F=0.670, P=0.652). The cross-sectional area of regenerated ST/GT was the largest at 3 months postoperatively ( P<0.05), and restored to the preoperative level at 12 and 24 months postoperatively (both P>0.05). Repeated measures analysis of variance showed that the elasticity values of the regenerated ST/GT were significantly different in terms of time effect, group effect, and interaction effect ( F=265.402, 33.015, 11.475; all P<0.001). The elasticity of regenerated ST/GT post-operation gradually increased over time. The flexion strength level of knee gradually improved post-operation(χ 2=34.83, P<0.001). The elasticity values of the regenerated ST and GT showed significant positive correlations with the flexion strength ( rs=0.755, 0.761; both P<0.001). Conclusions:HFUS discovers that most of ST/GT can be regenerated after being harvested for ACL reconstruction. The flexion strength and elasticity value of regenerated tendon recover gradually with time. It is suggested that the SWE can predict the recovery of biomechanical property of regenerated ST/GT.

Objective:To understand the serological characteristics of irregular antibodies in pregnant women and explore their clinical significance.Methods:From January 2017 to March 2022,151 471 pregnant women in Women and Children's Hospital of Chongqing Medical University were enrolled in this study,microcolumn gel card test was used for irregular antibody screening,and antibody specificity identification was further performed in some antibody-positive subjects.Results:The positive rate of irregular antibody screening in the enrolled pregnant women was 0.91％(1 375/151 471),0.23％(355/151 471)was detected in the first trimester,0.05％(71/151 471)in the second trimester,and 0.63％(949/151 471)in the third trimester.The positive rate of irregular antibody screening in the third trimester was significantly higher than that in the first and second trimester,and a significant increase in the number of positive cases was found in the third trimester than that in the second trimester.The analysis of agglutination intensity of 1 375 irregular antibody screening positive results showed that the weakly positive agglutination intensity accounted for 50.11％(689/1 375),which was the highest,the suspicious positive was 18.69％(257/1 375),and the positive was 31.20％(429/1 375).The significant difference in distribution of agglutination intensity was not observed between the first trimester group and the second trimester group,however,in the third trimester,the proportion of suspicious positive and weakly positive was lower than the first trimester,while,the proportion of positive was higher than the first trimester,and the difference was statistically significant(P＜0.001).Among the irregular antibody screening positive pregnant women,the proportion of pregnant women with pregnancy number ≥ 2 was significantly higher than that with pregnancy≤1.Among 60 pregnant women who underwent antibody identification,the distributions of the antibodies were as follows:Rh blood group system accounted for 23.33％(14/60),Lewis system 43.33％(26/60),Kidd system 3.33％(2/60),MNS system 16.67％(10/60),P1PK system 1.67％(1/60),autoantibodies 1.67％(1/60),and 4 cases was unable to identify(6.67％,4/60).Among specific antibodies,the anti-Lea was the most common(30.00％),followed by anti-E(16.67％)and anti-M(16.67％).Conclusion:The differences of irregular antibody serological characteristics exist in pregnant women from different regions with different genetic backgrounds,understanding the characteristics of irregular antibody in local pregnant women is of great significance for ensuring transfusion safety in pregnant women and preventing hemolytic disease of newborn.

Objective:To analyze the distribution characteristics of Rh phenotype in pregnant and postpartum women in Chongqing area,and to explore the clinical significance of Rh phenotype in pregnant and postpartum women and the feasibility of Rh phenotype compatible blood transfusion.Methods:The ABO blood group and Rh phenotype of 65 161 pregnant and postpartum women were detected by microcolumn gel method,and 48 122 males in the same period were taken as controls.The data were analyzed by Chi-square test.Results:There were 112 870 cases(99.64％)of RhD+in 113 283 samples.In RhD+cases,CCDee(48.39％)and CcDEe(32.88％)were the main phenotypes.The first case of D--phenotype in Chongqing area was detected.413 cases(0.36％)of RhD-were detected,with ccdee(52.78％)and Ccdee(33.41％)as the main phenotypes.Compared with RhD-group,RhD+group showed statistically significant difference in Rh phenotype distribution(P＜0.01).Among 65 161 maternal samples,the positive rate of 5 antigens of Rh blood group from high to low was D＞e＞C＞c＞E,and there was no significant difference compared with male samples(P＞0.05).There was no significant difference in the distribution of Rh phenotype between males and pregnant/postpartum women,as well as between pregnant/postpartum women with different ABO blood groups(P＞0.05).In pregnant and postpartum women,there was no significant difference in distribution of Rh phenotype among the normal pregnancy population,the population with adverse pregnancy history,the population using human assisted reproductive technology(ART)and the population with infertility(P＞0.05).There was no significant difference in the distribution of Rh phenotype between the 4 populations mentioned above and the inpatients in the local general Grade A hospitals and the blood donors(P＞0.05).In RhD positive pregnant and postpartum women,the probability of finding compatible blood for CcDEe phenotype was 100％,the probability of finding compatible blood for CCDee,CcDee and CCDEe phenotypes was 45％-60％,the probability of finding compatible blood for ccDEE,ccDEe and CcDEE phenotypes was 5％-10％,and the probability of finding compatible blood for other phenotypes was lower than 0.5％.The supply of blood with CCDee and ccDEE phenotypes can meet the compatible transfusions requirements of 7 Rh phenotypes in more than 99％of patients.Conclusion:Rh phenotype detection should be carried out for pregnant and postpartum women,and it is feasible to carry out Rh phenotype-matched or compatible blood transfusion for pregnant and postpartum women who need blood transfusion.

The detection of cancer markers is of great significance for the early diagnosis and subsequent treatment of cancer.However,the existing traditional detection methods have some limitations,especially in the early stages of cancer,thus is often difficult to detect in a timely and accurate manner.As an efficient detection technique,electrochemical sensors can meet the requirement of accurate detection of various cancer markers,provide strong support for early diagnosis of cancer,and have broad application prospects.MXene is a new two-dimensional material,which is widely used in electrochemical sensors because of its unique properties such as high electron transfer ability,high conductivity,large specific surface area,good biocompatibility and hydrophilicity and abundant surface chemical groups,etc.This paper reviewed the applications of electrochemical biosensors based on MXene composites in cancer marker detection in recent years,introduced the function of MXene in electrochemical biosensor,and discussed challenges and future development trends of MXene in the early diagnosis of cancer,aiming to provide reference for early detection of cancer.

AIM:This study utilized CRISPR/Cas9 technology to create Retnlb floxp knock-in mice,followed by the application of the Cre-LoxP recombination system to generate intestinal epithelial-specific Retnlb gene knockout mice(Retnlb-CKO).This model was developed to investigate the pathogenic mechanisms of Retnlb in inflammatory bowel disease.METHODS:Female and male C57BL/6N mice,aged 8 weeks with the Retnlbflox/+genotype,were housed togeth-er for breeding.Offsprings were screened to identify those with the Retnlbflox/flox genotype.These mice were then crossed with Vil1-Cre transgenic mice,which express Cre recombinase specifically in intestinal epithelial cells,resulting in Retnlb-flox/+,Cre+mice.Subsequent crosses between Retnlbflox/+,Cre+mice and Retnlbflox/flox mice produced Retnlbflox/flox,Cre+mice(Retnlb-CKO).Six 8-week-old Retnlbflox/flox,Cre+mice and their littermate Retnlbflox/flox mice were selected for experiments.RT-qPCR and immunohistochemistry were used to assess Retnlb mRNA and protein levels in colonic epithelium.Phenotypic observa-tions included body length,weight,diet,and reproductive capability.Tissue-to-body weight ratios were calculated to ana-lyze growth and development.Intestinal barrier integrity and colonic expression of inflammatory factors were evaluated.RESULTS:The conditional gene knockout mouse model with specific deletion of Retnlb in intestinal epithelial cells was successfully established and validated through genetic identification,mRNA and protein analysis.Compared to Retnlbflox/flox mice,Retnlb-CKO mice exhibited no significant differences in body length,weight,diet,or reproductive capability.There were no differences in the ratios of heart,liver,spleen,lung,kidney,and colon weight to body weight,nor were there morphological differences in various tissues.However,the mRNA expression of tight junction proteins ZO-1,Occlu-din,and Claudin3 in colon tissues of Retnlb-CKO mice was significantly reduced(P<0.01).PAS staining and immunohis-tochemistry revealed a significant decrease in the number of goblet cells and lysozyme-positive cells in the colon tissues of Retnlb-CKO mice(P<0.01).HE staining showed no obvious pathological change in colon tissues of Retnlb-CKO mice.RT-qPCR further demonstrated a significant downregulation of pro-inflammatory factors NLRP3,interleukin-6(IL-6),IL-1β,and tumor necrosis factor-α(TNF-α)in colon tissues(P<0.01),along with significant downregulation of inflamma-tion signaling pathway proteins TLR4,MyD88,and NF-κB(P<0.01).CONCLUSION:A conditional colon epithelial cell Retnlb gene knockout mouse model was successfully constructed and validated.The absence of Retnlb in colon cells led to impaired intestinal barrier function,decreased mRNA expression of pro-inflammatory factors in colon tissue,and downregulation of mRNA expression of inflammatory pathway proteins TLR4,MyD88,and NF-κB.

OBJECTIVE: To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). METHODS: The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored. RESULTS: The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients. CONCLUSION VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.
Adult ; Humans ; Retrospective Studies ; Neoplasm, Residual/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/adverse effects* ; Recurrence ; Leukemia, Myeloid, Acute/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*