Several molecular biomarkers (p16INK4a,Ki-67,and so on) are abnormally expressed in cervical precancerous lesions,many of which are involved in human papilloma virus (HPV)-induced molecular alterations.Cervical intraepithelial neoplasia (CIN) can not accurately predict the possibility of progress in precancerous lesions.Atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are often over-treated clinically,while it lacks accurate screening methods to identify the precancerous lesions with high possibility of progression.Combining cytology diagnosis with biomarkers can help predict the progress of precancerous lesions and distinguish benign lesions which are difficult to identify morphologically.It appears promising to consider biomarkers as potential cervical precancerous lesions screening method.

Objective:To compare the efficacy of endoscopy and surgery in chronic pancreatitis.Methods:CNKI, CBM, Wanfang, PubMed, Cochrane Library, Embase and Web of Science were searched to compared endoscopy and surgery for the clinical efficacy of chronic pancreatitis. Literatures were searched from the establishment of the database to August 14, 2022. Compared pain relief, clinical response to initial treatment, complications, endocrine/exocrine insufficiency, length of hospital stay and mean number of procedures between the two groups. Manager 5.4.1 software was used for data analysis. Odds ratio ( OR) or weighted mean difference ( WMD) was calculated with 95% confidence interval (95% CI). Results:A total of seven studies were included, including three randomized controlled trials and four retrospective studies with 708 patients. There were 513 males and 195 females. Endoscopic interventions were performed in 364 patients and 344 patients underwent surgery. The results of meta-analysis showed that the total pain relief rate ( OR=0.38, 95% CI: 0.24-0.59) and the complete pain relief rate ( OR=0.47, 95% CI: 0.29-0.77), short-term (1-1.5 years) pain relief rate ( OR=0.42, 95% CI: 0.24-0.74), clinical relief rate ( OR=0.23, 95% CI: 0.10-0.55) were better than the endoscopic group, and could significantly reduce the number of reoperation ( WMD=1.64, 95% CI: 0.89-2.40), and the difference was statistically significant (all P<0.05). There were no significant differences in complications, new-onset endocrine insufficiency, new-onset exocrine insufficiency and length of hospital stay between the endoscopy group and the surgical group (all P>0.05). Conclusion:Surgical intervention is superior to endoscopic treatment in controlling pain associated with chronic pancreatitis and in clinical relief after the first treatment, and can effectively reduce the number of reoperations.

Objective:To evaluate the epidemiology of bacterial bloodstream infections in patients submitted to hematologic wards in southern China.Methods:A total of 50 teaching hospitals were involved based on the China Antimicrobial Resistance Surveillance System. The data of clinical isolates from blood samples were collected from January 1, 2019, to December 31, 2019. Antimicrobial susceptibility testing was conducted by the Kirby-Bauer automated systems, and the results were interpreted using the CLSI criteria.Results:The data of 1,618 strains isolated from hematologic wards in 2019 were analyzed, of which gram-negative bacilli and gram-positive cocci accounted for 71.8% and 28.2%, respectively. Of those, the five major species were most often isolated, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, coagulase-negative staphylococcus, and Streptococcus viridans. The prevalence rates of methicillin-resistant strains in Staphylococcus aureus and coagulase-negative staphylococcus were 19.7% and 80.6%, respectively. No gram-positive cocci were resistant to vancomycin, linezolid, and teicoplanin, and none of the enterococci were resistant to linezolid. The resistance rate of S. viridans to penicillin G was 6.9%, and those to ceftriaxone and cefotaxime were more than 25%. The resistance rate of E. coli and K. pneumoniae in Enterobacteriaceae was higher in children than that in adults. The resistance rate of K. pneumoniae to meropenem was 14.1%. The resistant rate of Enterobacter cloacae to carbapenem was more than 25%. P. aeruginosa was more sensitive to more antibiotics than 80%, but the resistance rate to meropenem in children was higher than that in adults (11.8% vs. 6.5%). The proportion of gram-positive cocci in the ICU and respiratory departments was higher than that in the hematology department. The detection rates of carbapenem-resistant E. coli and K. pneumoniae in the respiratory department were the lowest with 0.3% and 3.7%, respectively, while those of CRPA and CRAB in the hematology department were the lowest with 8.3% and 25.8%, respectively. The detection rate of all carbapenem-resistant organisms in the ICU was the highest among the three departments.Conclusion:The etiology and drug resistance of bacteria from blood samples in the hematology department are different from those in the ICU and respiratory departments. The proportions of K. pneumoniae, P. aeruginosa, E. cloacae, and S. viridans dominating in the department of Hematology were significantly higher than those in the ICU and respiratory departments in Guangdong region.

In recent years， transcatheter arterial chemoembolization （TACE） has emerged as a common treatment modality for the treatment of hepatocellular carcinoma （HCC）. However， with the ongoing development of embolic agent techniques， the new advances in microspheres and nanoparticles have brought new hope for improving the efficacy and safety of TACE. This article reviews the latest advances and applications of microspheres and nanoparticles in TACE for HCC. First， this article introduces the background of TACE as a therapeutic approach and the emergence of microsphere and nanoparticle techniques， and then it describes the application of various types of microspheres and nanoparticles in TACE and discusses the requisite attributes of an ideal embolic agents. The article focuses on the advances in material science and engineering， as well as the clinical efficacy of drug-eluting microspheres and nanoparticles versus conventional TACE. Furthermore， it discusses the importance of radiological examination in TACE and summarizes the research advances in the radiopaque and magnetic resonance-visible embolic agents. This article also explores the future development directions and challenges of TACE. It also points out the combination of microspheres and nanoparticles with other treatment modalities， the application of personalized and precision medicine in TACE， and the potential regimen of TACE in clinical translation， and meanwhile， it raises the issues of ethics and regulation that need to be further discussed. It is believed that microspheres and nanoparticles have a potential effect in TACE， which provides a theoretical basis and technical support for innovating HCC treatment regimens and improving the prognosis of patients through TACE interventions.

Objective:To construct a novel dual-specific antibody targeting human CD123 (CD123 DuAb) and study its effects in acute myeloid leukemia (AML) .Methods:Based on the variable region of the CD123 monoclonal antibody independently developed at our institution, the CD123 DuAb expression plasmid was constructed by molecular cloning and transfected into ExpiCHO-S cells to prepare the antibody protein. Through a series of in vitro experiments, its activation and proliferation effect on T cells, as well as the effect of promoting T-cell killing of AML cells, were verified.Results:① A novel CD123 DuAb plasmid targeting CD123 was successfully constructed and expressed in the Expi-CHO eukaryotic system. ②The CD123 DuAb could bind both CD3 on T cells and CD123 on CD123 + tumor cells. ③When T cells were co-cultured with MV4-11 cells with addition of the CD123 DuAb at a concentration of 1 nmol/L, the positive expression rates of CD69 and CD25 on T cells were 68.0% and 44.3%, respectively, which were significantly higher than those of the control group ( P<0.05). ④Co-culture with CD123 DuAb at 1 nmol/L promoted T-cell proliferation, and the absolute T-cell count increased from 5×10 5/ml to 3.2×10 6/ml on day 9, and CFSE fluorescence intensity decreased significantly. ⑤ With the increase in CD123 DuAb concentration in the culture system, T-cell exhaustion and apoptosis increased. When the CD123 DuAb was added at a concentration of 1 nmol/L to the culture system, the proportion of CD8 + PD-1 + LAG-3 + T cells was 10.90%, and the proportion of propidium iodide (PI) - Annexin Ⅴ + T cells and PI + Annexin Ⅴ + T cells was 18.27% and 11.43%, respectively, which were significantly higher than those in the control group ( P<0.05). ⑥ The CD123 DuAb significantly activated T cells, and the activation intensity was positively correlated with its concentration. The expression rate of CD107a on T cells reached 16.05% with 1 nmol/L CD123 DuAb, which was significantly higher than that of the control group ( P<0.05). ⑦The CD123 DuAb promoted cytokine secretion by T cells at a concentration of 1 nmol/L, and the concentration of IFN-γ and TNF-α in the supernatant of the co-culture system reached 193.8 pg/ml and 169.8 pg/ml, respectively, which was significantly higher than that of the control group ( P<0.05). ⑧When CD123 DuAb was added at a concentration of 1 nmol/L to the co-culture system of T cells and CD123 + tumor cells, the killing intensity of T cells significantly increased, and the residual rates of CD123 + MV4-11 cells, CD123 + Molm13 cells, and CD123 + THP-1 cells were 7.4%, 6.7%, and 14.6% on day 3, respectively, which were significantly lower than those in the control group ( P<0.05) . Conclusion:In this study, a novel CD123 DuAb was constructed and expressed. In vitro experiments verified that the DuAb binds to CD123 + tumor cells and T cells simultaneously, promotes T-cell activation and proliferation, and facilitates their anti-leukemia effect, which provides a basis for further clinical research.

Objective To understand the changing distribution and antimicrobial resistance profiles of Klebsiella strains in 52 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Antimicrobial susceptibility testing was carried out according to the unified CHINET protocol.The susceptibility results were interpreted according to the breakpoints in the Clinical & Laboratory Standards Institute(CLSI)M100 document.Results A total of 241,549 nonduplicate Klebsiella strains were isolated from 2015 to 2021,including Klebsiella pneumoniae(88.0％),Klebsiella aerogenes(5.8％),Klebsiella oxytoca(5.7％),and other Klebsiella species(0.6％).Klebsiella strains were mainly isolated from respiratory tract(48.49±5.32)％.Internal medicine(22.79±3.28)％,surgery(17.98±3.10)％,and ICU(14.03±1.39)％were the top 3 departments where Klebsiella strains were most frequently isolated.K.pneumoniae isolates showed higher resistance rate to most antimicrobial agents compared to other Klebsiella species.Klebsiella isolates maintained low resistance rates to tigecycline and polymyxin B.ESBLs-producing K.pneumoniae and K.oxytoca strains showed higher resistance rates to all the antimicrobial agents tested compared to the corresponding ESBLs-nonproducing strains.The K.pneumoniae and carbapenem-resistant K.pneumoniae(CRKP)strains isolated from ICU patients demonstrated higher resistance rates to majority of the antimicrobial agents tested than the strains isolated from non-ICU patients.The CRKP strains isolated from adult patients had higher resistance rates to most of the antimicrobial agents tested than the corresponding CRKP strains isolated from paediatric patients.Conclusions The prevalence of carbapenem-resistant strains in Klebsiella isolates increased greatly from 2015 to 2021.However,the Klebsiella isolates remained highly susceptible to tigecycline and polymyxin B.Antimicrobial resistance surveillance should still be strengthened for Klebsiella strains.