Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/10⁵, 95% UI: (1.49/10⁵, 4.07/10⁵)], prevalence [0.64/10⁵, 95% UI: (0.37/10⁵, 1.02/10⁵)], mortality [0.51/10⁵, 95% UI: (0, 1.80/10⁵)] and DALYs rates of VL [33.81/10⁵, 95% UI: (0.06/10⁵, 124.09/10⁵)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/10⁵, 95% UI: (0.45/10⁵, 0.72/10⁵); 0.14/10⁵, 95% UI: (0.11/10⁵, 0.18/10⁵)] than among women [0.27/10⁵, 95% UI: (0.21/10⁵, 0.33/10⁵); 0.06/10⁵, 95% UI: (0.05/10⁵, 0.08/10⁵)], and the highest mortality of VL was found among children under 5 years of age [0.24/10⁵, 95% UI: (0.08/10⁵, 0.66/10⁵)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/10⁵, 0.03/10⁵, 0.02/10⁵ and 1.44/10⁵ in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.

One of the technical bottlenecks limiting the high yield of 1,4-butanediamine is the insufficient tolerance of strains to 1,4-butanediamine. Enhancing the tolerance of strains to 1,4-butanediamine is therefore a primary challenge that needs to be addressed for the construction of strains with high yields of 1,4-butanediamine. Staphylococcus pasteuri 326180 exhibits exceptional tolerance to high-concentration 1,4-butanediamine, serving as both an ideal model for studying the mechanism underlying the 1,4-butanediamine tolerance and a novel host for constructing strains capable of efficiently producing 1,4-butanediamine. However, for both the research on the tolerance mechanism and the modification of chassis strains, gene editing of S. pasteuri needs to be carried out at the molecular level. The research objective of this paper is to establish a genetic manipulation system for S. pasteuri, laying foundation for subsequent studies on tolerance mechanism and the modification of chassis strains. This study systematically optimized the electroporation conditions, including key parameters such as the growth phase of cells, electric field strength, electroporation buffer, and recovery medium, successfully establishing an electroporation method for S. pasteuri. Additionally, we constructed the gene editing plasmid pCpfOA by replacing the resistance expression cassette, optimized the selection markers for gene editing, and finally established a CRISPR/Cpf1-based gene editing technology for S. pasteuri, achieving an editing efficiency of 90%. The genetic manipulation system of S. pasteuri established in this study provides technical support for research into the tolerance mechanism of this bacterium and the genetic modification of chassis strains.
Staphylococcus/drug effects* ; Gene Editing/methods* ; Electroporation/methods* ; Plasmids/genetics* ; CRISPR-Cas Systems ; Genetic Engineering/methods*

OBJECTIVE To investigate the mechanism by which Ginkgo flavone aglycone （GA） reduces the cardiotoxicity of doxorubicin （DOX） based on transcriptomics and proteomics. METHODS Thirty-six mice were randomly assigned to control group （CON group， tail vein injection of equal volume of physiological saline every other day+daily intragastric administration of an equal volume of physiological saline）， DOX group （tail vein injection of 3 mg/kg DOX every other day）， and GDOX group （daily intragastric administration of 100 mg/kg GA+tail vein injection of 3 mg/kg DOX every other day）， with 12 mice in each group. The administration of drugs/physiological saline was continued for 15 days. Mouse heart tissues were collected for RNA-Seq transcriptomic sequencing and 4D-Label-free quantitative proteomic analysis to screen differentially expressed genes and proteins， which were then subjected to Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. The expression levels of Apelin peptide （Apelin）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） mRNA and protein in mouse heart tissues， as well as the phosphorylation levels of PI3K and Akt proteins， were verified. H9c2 cardiomyocytes were divided into control group （CON group）， DOX group （2 μmol/L）， and GDOX group （2 μg/mL GA+2 μmol/L DOX） to determine cell viability and the levels of key glycolytic substances in the cells. RESULTS Six common pathways were identified from transcriptomics and proteomics， including the Apelin signaling pathway， the PI3K-Akt signaling pathway， and insulin resistance. Among them， the Apelin and PI3K-Akt signaling pathways were the most enriched in terms of gene numbers. Target validation experiments showed that compared to the CON group， the relative expression of Apelin， PI3K and Akt mRNA and protein levels， as well as the phosphorylation levels of PI3K and Akt proteins， were significantly decreased in the DOX group （P＜0.05 or P＜0.01）. The relative expression of Apelin， PI3K and Akt mRNA and the phosphorylation levels of PI3K and Akt proteins were significantly increased in the GDOX group as compared with the DOX group （P＜0.05 or P＜0.01）. Cellular experiments indicated that compared to the CON group， cell viability in the DOX group was significantly decreased （P＜0.05）， the relative uptake of glucose and the relative production of pyruvate and lactate were significantly increased （P＜0.05）， and the relative production of ATP was significantly reduced （P＜0.05）. Compared to the DOX group， cell viability in the GDOX group was significantly increased （P＜ 0.05）， and the relative production of pyruvate and lactate was significantly reduced （P＜0.05）. CONCLUSIONS GA may alleviate DOX-induced cardiotoxicity by upregulating the mRNA and protein expression of Apelin， PI3K， and Akt in heart tissues， and regulating glycolytic processes.

OBJECTIVE To establish the quality control method for the roots and rhizoma of Toricellia angulata. METHODS The properties of the roots and rhizoma of T. angulata were observed and microscopic identification was conducted. The moisture， total ash， acid-insoluble ash and ethanol-soluble extract were examined according to the method stated in the 2020 edition of Chinese Pharmacopoeia （part Ⅳ）. HPLC fingerprints of 11 batches of the roots and rhizoma of T. angulata were established， common peaks were identified and the similarity was evaluated by using the Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition）. The contents of coniferin， syringin， chlorogenic acid， （+）-syringaresinol-O-β-D-glucopyranoside and syringaresinol were determined by HPLC. RESULTS The properties and microscopic identification of the roots and rhizoma of T. angulata were obvious. The average contents of moisture， total ash， acid-insoluble ash and ethanol-soluble extract were 7.54%， 2.18%， 0.15% and 7.81%， respectively. There were 16 common peaks marked in the HPLC fingerprints of 11 batches of the roots and rhizoma of T. angulata， with similarities of 0.856-0.960； five of them were identified， such as coniferin， syringin， chlorogenic acid， （+）-syringaresinol-O-β-D-glucopyranoside and syringaresinol. The contents of the above five components were 0.047 2-0.401 6， 0.836 8-8.697 9， 1.245 3-10.950 0， 0.139 0-0.437 8 and 0.016 4-0.635 3 mg/g， respectively. CONCLUSIONS The established method is stable and accurate， which can be used for the quality control of the roots and rhizoma of T. angulata. It is preliminarily proposed that the moisture in the roots and rhizoma of T. angulata is not more than 11.0%， the total ash is not more than 4.0%， the ethanol-soluble extract is not less than 5.0%， the contents of coniferin， syringin， chlorogenic acid， （+）-syringaresinol-O-β-D- glucopyranoside and syringaresinol are not less than 0.04，0.83， 1.24， 0.13， 0.01 mg/g， respectively.

Objective To explore the effect and safety of magnetic resonance imaging and transrectal ultrasound (mpMRI-TRUS) image fusion targeted transperineal biopsy technique using electromagnetic needle tracking under local anesthesia. Methods We retrospectively analyzed the clinical and pathological data of 81 patients with mpMRI-TRUS image fusion targeted transperineal prostate biopsy using electromagnetic needle tracking under local anesthesia. Visual analog scale (VAS) and visual numeric scale (VNS) were used to evaluate the pain level and satisfaction of patients during prostate biopsy (VAS-1 and VNS-1), one hour after puncture (VAS-2 and VNS-2), and one day after surgery (VAS-3 and VNS-3). The perioperative clinical data and tumor positive rate of postoperative biopsy were recorded. Results The average prostate volume of 81 patients was 53.39±29.46 cm³. The PSA values of patients with PI-RADS scores of 2, 3, 4, and 5 were 9.14±2.31, 9.95±4.10, 14.77±6.36, and 32.17±24.39 ng/ml, respectively. The scores of VAS-1, VAS-2, and VAS-3 were 1.70±0.73, 1.16±0.58, and 0.53±0.55, respectively; the scores of VNS-1, VNS-2, and VNS-3 were 2.74±0.44, 3.69±0.46, and 3.84±0.37, respectively. The average surgical time was 17.47±3.44 minutes. Postoperative pathological results showed that the tumor positive rate of targeted prostate biopsy was 64.20%. According to the PI-RADS score for subgroup analysis, the tumor positive rates of patients with PI-RADS scores of 2, 3, 4, and 5 were 21.43%, 44.44%, 61.11%, and 96.77%, respectively. After transperineal prostate biopsy, gross hematuria occurred in 19.75% patients, and urinary retention occurred in 3.70%. The latter were relieved after symptomatic treatment. All patients did not experience complications, such as perineal puncture area hematoma, urinary tract infection, hematospermia, hematoma in perineal puncture area, urinary tract infection, hematospermia, vagus nerve reaction, or septic shock. Conclusion For suspected prostate cancer patients, mpMRI-TRUS image fusion targeted transperineal biopsy technique using electromagnetic needle tracking under local anesthesia is a feasible and easily tolerated surgical procedure. It has good safety and high tumor positive-detection rate, indicating that this technique is worthy of further clinical promotion and application.

Objective:To analyze the current situation of middle-level cadres in functional departments of scientific research institutes and to construct a job competency model for middle-level cadre.Methods:A cluster random sampling method was used to conduct a questionnaire survey in March 2022 on the satisfaction level of middle-level cadres in the functional departments of the Institute of Blood Transfusion of the Chinese Academy of Medical Sciences,a mid-level cadre competency questionnaire survey was conducted to collect data among functional department personnel of scientific research institutes affiliated to the Chinese Academy of Medical Sciences and Peking Union Medical College.The principal component analysis method was used to extract factors,and the maximum variance rotation method was used to conduct exploratory factor analysis to construct a competency model.Results:The Middle-level cadres in scientific research institutes had problems such as old age,traditional management style,etc.The competency model of middle-level cadres in functional departments of scientific research institutes included 3 main competencies:responsibility taking ability,communication ability and learning execution ability,and 34 competency factors.Conclusion:The competency model of middle-level cadres in functional departments of scientific research institutes can provide basis and reference for the selection and appointment,education and training,performance management and career planning of middle-level cadres in scientific research institutes.

OBJECTIVE To investigate the potential mechanism of the effect of ginkgo flavone aglycone （GA） against doxorubicin （DOX）-induced cardiotoxicity. METHODS The male ICR mice were randomized into control group （CON group）， model group （DOX group） and GA+DOX group （GDOX group）， with 12 mice in each group. The DOX group was injected with DOX solution at a dose of 3 mg/kg via tail vein every other day， and the GDOX group was given GA suspension intragastrically at a dose of 100 mg/kg every day+DOX solution at a dose of 3 mg/kg via tail vein every other day， for 15 consecutive days. After the end of administration， the serum levels of aspartate aminotransferase（AST）， creatine kinase（CK）， creatine kinase isoenzyme（CK- MB） and lactate dehydrogenase（LDH） in mice were detected in each group. Based on the metabolomics method， UHPLC-Q- Exactive Orbitrap HRMS method was used； based on principal component analysis （PCA） and orthogonal partial least squares- discriminant analysis （OPLS-DA）， the differentially expressed metabolites （DEMs） were screened using the criteria of variable importance in the projection≥1， fold change of peak area＞1 and P＜0.05； biological analysis was conducted based on databases such as HMDB and PubChem. RESULTS Compared with CON group， serum levels of AST， CK， CK-MB and LDH were increased significantly in DOX group （P＜0.05）； compared with DOX group， the serum levels of the above indicators （except for CK-MB） were decreased significantly in GDOX group （P＜0.05）. PCA and OPLS-DA showed that myocardial tissue samples of CON group， DOX group and GDOX group were isolated completely. After database matching， 37 common DEMs were identified， among which 17 DEMs were significantly up-regulated in the DOX group and significantly down- regulated in the GDOX group， and 8 DEMs were significantly down-regulated in the DOX group and significantly up-regulated in the GDOX group； pathway enrichment involved the biosynthesis of unsaturated fatty acids， arachidonic acid metabolism， linoleic acid metabolism， taurine and hypotaurine metabolism； the key metabolites in the above pathways included docosahexaenoic acid， arachidonic acid， phosphatidylcholine （16∶0/18∶3） and taurine. CONCLUSIONS GA may regulate the biosynthesis of unsaturated fatty acids， arachidonic acid metabolism and other metabolic pathways by acting on the core metabolites such as docosahexaenoic acid and arachidonic acid， thus alleviating the cardiotoxic effects of DOX.

Objective To explore the efficacy and safety of multi-parametric magnetic resonance imaging and transrectal ultrasonography(mpMRI-TRUS)fusion targeted transperineal biopsy(TPB)under local anesthesia(LA)with"one-plane three-point"dual probe ultrasound localization.Methods Clinical data of 134 suspected prostate cancer(PCa)patients treated with this method in our hospital during Jan.and Sep.2023 were retrospectively analyzed.The same doctor applied visual analog scale(VAS)and visual digital scale(VNS)to evaluate the pain level and satisfaction of patients during TPB(VAS-1 and VNS-1)and 1 hour after TPB(VAS-2 and VNS-2),and recorded the perioperative clinical data and detection rate of clinically significant prostate cancer(csPCa).Results VAS-1 score was(1.60±0.68)and VAS-2 score was(1.13±0.55);VNS-1 score was(2.84±0.41),and VNS-2 score was(3.74±0.44).The operation time was(16.12±3.35)minutes.The postoperative pathological results showed that the detection rate of csPCa was 65.67％(88/134).According to the PI-RADS score in subgroup analysis,the detection rates of patients with PI-RADS scores of 2,3,4,and 5 were 23.08％(6/26),52.94％(18/34),62.50％(15/24)and 98.00％(49/50),respectively.After TPB,gross hematuria occurred in 20.90％(28/134)patients,and urinary retention occurred in 4.00％(5/125)patients,which were relieved after symptomatic treatment.No complications such as perineal puncture area hematoma,urinary tract infection,hematospermia,vagal nerve reaction,and septic shock occurred.Conclusion The mpMRI-TRUS fusion targeted TPB under LA with"one-plane three-point"dual probe ultrasound localization provides a feasible and tolerable surgical procedure for suspected PCa patients with a high detection rate of csPCa,which is worthy of further clinical promotion and application.

Objective To explore the feasibility and accuracy of neutrophil-to-lymphocyte ratio(NLR)in the prediction of testicular torsion(TT)in children with acute scrotal pain.Methods A retrospective case-control study was performed on 158 pediatric patients with ultrasound suspicion of TT who underwent surgical testicular examination during Jan.2017 and Jan.2024.The patients were divided into TT group and non-TT group.Clinical data and laboratory data at admission were analyzed.Sensitivity and specificity of NLR to TT were determined with the area under the curve(AUC)represented on the receiver operating characteristic(ROC)curves.Results There were with no statistically significant differences in clinical data between the two groups(P＞0.05).The NLR was significantly higher in the TT group than in the non-TT group[(4.82±2.37)vs.(2.85±0.75),P＜0.05].The optimal cut-off value of TT predicted by NLR was 2.07,the AUC was 0.809(95％CI:0.709-0.909),and the sensitivity and specificity were 97.9％and 93.3％,respectively,which were significantly higher than other factors.Conclusion For suspicious ultrasound diagnosis of pediatric acute scrotal pain cases,NLR can be used to predict the possibility of TT and may help to evaluate the urgent surgical treatment in these patients.

Objective To explore the application value of mpMRI-TRUS multi-modal image fusion transperineal biopsy technique using electromagnetic needle tracking under local anesthesia combined with rapid paraffin-embedded section of small specimen in the diagnosis of prostate cancer.Methods The clinicopathological data of 138 patients with PI-RADS score≥3 who underwent mpMRI-TRUS image fusion transperineal biopsy using electromagnetic needle tracking under local anesthesia were retrospectively analyzed.AI technology was used to fuse mpMRI and TRUS multi-mode images,and two-core targeted biopsies were performed on suspicious lesions,followed by 12-core systematic biopsies.The specimens obtained from targeted biopsies were sent for rapid paraffin-embedded section pathological examination,and the detection rates of csPCa were compared.Results The detection rate of csPCa in 138 patients was 71.01% .The detection rates of csPCa in targeted biopsies and systematic biopsies were 62.32% and 70.29%,respectively(P=0.20).The detection rate of combined biopsies was higher than those of targeted biopsies and systematic biopsies,but the difference was not statistically significant(P>0.05).The detection rates of csPCa in targeted biopsies,systematic biopsies,and combined biopsies in patients with PI-RADS score 3 were 30.95%,38.10%,and 40.48%,respectively;and the percentages were 52.94%,61.76%,and 61.76% in patients with PI-RADS score 4,respectively;and the percentages were 90.32%,96.77%,and 96.77% in patients with PI-RADS score 5,respectively,without statistically significant difference(all P>0.05).In the subgroups with PI-RADS scores of 3,4,and 5,the missed diagnosis rates of csPCa by targeted biopsies were 23.53%,14.29%,and 6.67%,respectively.Conclusion For patients with suspected prostate cancer and PI-RADS v2.1 score≥3,transperineal biopsy using electromagnetic needle tracking combined with rapid paraffin-embedded section of small specimen can obtain pathological results rapidly and has good diagnostic accuracy.However,combined biopsy is still the most suitable method for the diagnosis of prostate cancer at present.