italic>Salmonella has emerged as a promising tumor-targeting strategy in recent years due to its good tumor targeting ability and certain safety. In order to further optimize its therapeutic effect, scientists have tried to modify Salmonella, including its attenuation and drug loading. This paper summarizes the mechanism and research progress of Salmonella-mediated targeted tumor therapy, and introduces the strategies and related progress of its modification and optimization. At the same time, the advantages, current challenges and future development directions of Salmonella-mediated tumor therapy are summarized.

Objective To investigate the expressions of H3.3G34W,p63 and SATB2 in giant cell tumor of bone(GCTB)and the effect and value of their combined application in the diagnosis of GCTB.Methods We collected the samples and medical records of 54 cases of GCTB and 83 cases of non-giant cell tumor of bone(14 cases of aneurysmal bone cyst,16 cases of chondroblastoma and 53 cases of non-ossifying fibroma)diagnosed between 2020 and 2022 in the Department of Pathology of Honghui Hospital Affiliated to Xi'an Jiaotong University.The expressions of H3.3G34W,p63 and SATB2 were detected by EliVision immunohistochemical method.X2 test was used to determine whether there are significant differences in the positive rates of H3.3G34W,p63 and SATB2 among all the groups.The combined diagnostic model including H3.3G34W,p63 and SATB2 was established by Logistic regression analysis,and the diagnostic value of the model was evaluated by ROC curve analysis.Results The positive rates of H3.3G34W,p63 and SATB2 in GCTB group were 81.5％,90.7％and 92.6％,respectively;the positive rates in NGCTB group were 2.4％,28.9％and 62.7％.Compared with NGCTB group,the age of GCTB group was significantly older[(41.222±14.849)vs.(16.566±9.439),P＜0.001],and the prevalence was higher in women than in men(51.9％vs.48.1％,P＜0.001).In addition,compared with the NGCTB group,the positive rates of H3.3G34W(81.5％vs.2.4％,P＜0.001),p63(90.7％vs.28.9％,P＜0.001)and SATB2(92.6％vs.62.7％,P＜0.001)were significantly higher in the GCTB group.Univariate regression analysis built a univariate prediction modeland ROC curve analysis showed that age(AUC=92.9％,P＜0.001),sex(AUC=64.5％,P=0.004),H3.3G34W positive rate(AUC=89.5％,P＜0.001),p63 positive rate(AUC=80.9％,P＜0.001)and SATB2 positive rate(AUC=65.0％,P=0.003)were independent predictors of diagnosis of giant cell tumor of bone.Multivariate regression analysis(Logistic)constructed a hybrid prediction model.ROC curve analysis suggested that the hybrid model showed better prediction value than the single factor model(AUC=98.4％,P＜0.001).Conclusion H3.3G34W,p63 and SATB2 are effective molecular markers for the diagnosis of GCTB,and their combined application can improve the prediction efficiency of the diagnosis of GCTB.

Objective To isolate the Japanese encephalitis virus carried by Culex tritaeniorhynchus in Dongchuan District of Yunnan Province and analyze its molecular characteristics, so as to provide insights into the prevention and control of Japanese encephalitis in Yunnan Province. Methods Mosquito specimens were collected using mosquito-trapping lamps from pig farms in Batang Village and Xiaoxin Village, Dongchuan District, Kunming City, Yunnan Province in July 2016, and the mosquito species was identified according to the mosquito morphology. Then, 60 to 100 mosquitoes of each species served as a group and were ground. Baby hamster kidney-21 (BHK-21) cells and Aedes albopictus clone C6/36 cells were used for virus isolation, and positive isolates were identified using flavivirus primers. The positive isolates were amplified using reverse transcription polymerase chain reaction (RT-PCR) assay with 15 pairs of specific primers covering the full length of the genotype I Japanese encephalitis virus, and DNA sequence assembly was performed using the software SeqMan in the DNASTAR package. The obtained sequences were aligned with the complete sequences of 38 Japanese encephalitis virus downloaded from the GenBank with the software MegAlign, and the nucleotide and amino acid homology analyses of the obtained sequences were performed. The difference in amino acid sites was analyzed with the software GeneDoc, and phylogenetic trees were created based on the sequences of the coding region and E protein of the isolated Japanese encephalitis virus with the software Mega X. In addition, the secondary and tertiary structures of the E protein of the Japanese encephalitis virus were predicted using the online tool SOPMA and the software Swiss-Model. Results A total of 5 820 mosquitoes were collected and 3 843 Cx. tritaeniorhynchus (66.03%) were identified according to the mosquito morphology. A positive virus isolate, termed YNDC55-33, was isolated from Cx. tritaeniorhynchoides following batches of virus isolation from mosquito specimens, and cytopathic effect was observed following inoculation into BHK-21 and C6/36 cells. The YNDC55-33 virus isolate was successfully amplified with the flavivirus primes, and a long sequence containing 300 nucleotides was obtained. Following sequence alignment using the BLAST tool, the sequence of the YNDC55-33 virus isolate had high homology with that of the genotype I Japanese encephalitis virus. A long sequence with 10 845 nucleotides in length, which encoded 3 432 amino acids, was obtained by splicing the full sequence of the YNDC55-33 virus isolate. Phylogenetic analysis based on the whole-genome sequence and E gene sequence of the YNDC55-33 virus isolate showed that the new YNDC55-33 virus isolate was most closely related to the genotype I Guizhou isolate (GenBank accession number: HM366552), with nucleotide homology of 98.5% and amino acid homology of 99.4%, and the YNDC55-33 virus isolate shared 97.96% ± 0.33% nucleotide homology and 99.35% ± 0.08% amino acid homology with other genotype I Japanese encephalitis virus isolates, and < 90% nucleotide homology and < 98% amino acid homology with other genotypes of Japanese encephalitis virus. The YNDC55-33 virus isolate and the live attenuated virus vaccine candidate SA14-14-2 isolate differed at 16 amino acid sites on E gene, and 7 out of 8 key amino acid sites related to neurovirulence. The secondary and tertiary structures of the E protein of the YNDC55-33 virus isolate were predicted to be characterized by random coils. Conclusions A genotype I Japanese encephalitis virus was isolated from Cx. tritaeniorhynchus in Dongchuan District, Kunming City. This virus isolate and the live attenuated virus vaccine candidate SA14-14-2 isolate does not differ at antigenic epitopes-related key amino acid sites, and the major protein structure of the virus isolate is random coils. This study adds new data for the epidemiological distribution of Japanese encephalitis virus in Yunnan Province, which may provide insights into the prevention and control of Japanese encephalitis in the province.

[Objective] To analyze the influencing factors of postoperative patency of longitudinal single suture intussusception microsurgical vasoepididymostomy, to provide reference for improving the repetition rate. [Methods] The clinical data of 82 patients with epididymal obstructive azoospermia who underwent longitudinal single suture intussusception microsurgical vasoepididymostomy in our hospital during Sep.2020 and Jan.2023 were retrospectively analyzed.The postoperative patency and spouse pregnancy were followed up by face to face and / or telephone interview.The effects of age, course of disease, body mass index (BMI), previous medical history (epididymitis, operation history, none), preoperative seminal plasma elastase (SPE) level, anastomosis site, unilateral and bilateral lesion, sperm quality, operation time and hospital stay on the postoperative patency rate were analyzed. [Results] All operations were successful, the follow-up rate was 95.12% (78/82), 78 were married, and the postoperative patency was 78.21% (61/78). Of the 61 patients who achieved patency, 56 were married, and the natural pregnancy rate of spouse was 45.21% (33/73). Univariate analysis showed that patients with age <30 years, course of disease <2 years, preoperative SPE level <290 ng/mL, bilateral anastomosis, body or tail anastomosis and motile sperm had higher postoperative patency rate (P>0.05). BMI, previous history, the number of motile sperms examined by epididymal fluid, the length of operation and hospital stay had no significant effects on postoperative patency (P>0.05). The results of multivariate logistic regression analysis showed that preoperative SPE level (OR=0.998, 95%CI: 0.997-1.000, P=0.008) and (OR=10.724, 95%CI: 2.243-51.283, P=0.003) were significantly correlated with postoperative patency. [Conclusion] The preoperative SPE level and anastomosis site are significant influencing factors of postoperative patency, which is higher in patients with age <30 years, course of disease <2 years, preoperative SPE level <290 ng/mL, bilateral anastomosis, body or tail anastomosis and motile sperm.

Objective To develop and validate a deep learning model for automatic identification of liver CT contrast-enhanced phases.Methods A total of 766 patients with liver CT contrast-enhanced images were retrospectively collected.A three-phase classification model and an arterial phase(AP)classification model were developed,so as to automatically identify liver CT contrast-enhanced phases as early arterial phase(EAP)or late arterial phase(LAP),portal venous phase(PVP),and equilibrium phase(EP).In addition,221 patients with liver CT contrast-enhanced images in 5 different hospitals were used for external validation.The annotation results of radiologists were used as a reference standard to evaluate the model performances.Results In the external validation datasets,the accuracy in identifying each enhanced phase reached to 90.50%-99.70%.Conclusion The automatic identification model of liver CT contrast-enhanced phases based on residual network may provide an efficient,objective,and unified image quality control tool.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To develop an expert consensus on subcutaneous injection nursing for allergic asthma in children,standardize nursing practice to reduce the occurrence of related adverse reactions.Methods The clinical guideline,expert consensus,systematic review,evidence summary and original research on subcutaneous injection of monoclonal antibody drug for children with allergic asthma were comprehensively searched in domestic and foreign databases.The time limit for retrieval was from the establishment of databases until August 2023.Combined with clinical practice experience,the first draft of the consensus was formed.From December 2023 to February 2024,27 experts were invited to conduct 2 rounds of expert letter consultation,revise and improve the contents of the first draft,and expert demonstration was conducted,and finally a consensus final draft was formed.Results The effective recovery rate of the 2 rounds of letter consultation questionnaires was 100％;the authority coefficient of experts was 0.88;the judging basis coefficient was 0.93;the familiarity coefficient was 0.83.In the 2 rounds of correspondence,the Kendall concordant coefficients of expert opinions were 0.241 and 0.252,respectively(P＜0.001 for both).The consensus includes 6 parts,including personnel management,environmental layout,indications and contraindications,subcutaneous injection operation norms,identification and treatment of adverse reactions,and health education.Conclusion The consensus is strongly scientific and practical,and can provide guidance for nursing practice of subcutaneous injection of monoclonal antibodies in children with allergic asthma.

Objective:To analyze the factors for low libido in male patients with sexual dysfunction and provide some evidence for the clinical diagnosis and treatment of the condition.Methods:We retrospectively analyzed the clinical data on 111 cases of sex-ual dysfunction(including disorders in erection,ejaculation or libido)treated in the Zhengzhou University First Hospital from June to September 2023.According to the patients'complaints of low libido or accompanied symptoms,we divided them into a normal libido group(n=68)and a low libido(n=43),obtained their scores on IIEF-5,Premature Ejaculation Diagnostic Tool(PEDT),13-1-tem Self-Rating Libido Scale for Males(SRLS-M),Patients'Health Questionnaire-9(PHQ-9)and General Anxiety Disorder-7(GAD-7),examined the levels of the sexual hormones FSH,LH,PRL,T,free testosterone(fT),E2,?insulin-like growth factor 1(IGF-1)and growth hormone(GH),compared the basic parameters between the two groups,and analyzed their correlation with the libido values.Results:The IIEF-5,PEDT and libido scores and IGF-1 level were significantly higher and the GAD-7 score remark-ably lower in the normal than in the low libido group(P＜0.05),but no statistically significant differences were observed between the two groups in the PHQ-9 score and the levels FSH,LH,PRL,T,fT,E2,T/E2 and GH(P＞0.05).The libido value was correla-ted positively with the I1EF-5(r=0.28,P＜0.01)and PEDT scores(r=0.29,P＜0.01)and IGF-1 level(r=0.23,P＜0.05),but negatively with the GAD-7 score(r=-0.21,P＜0.05).Conclusion:Low libido results from multiple factors,which cannot be fully explained by sexual hormone levels but is closely related to the decreased level of IGF-1 and severity of ED and anxiety.

Objective:To investigate the therapeutic effect of Ningmitai Capsules(NMT)on chronic prostatitis/chronic pel-vic pain syndrome(CP/CPPS)and its action mechanism.Methods:We equally randomized fifteen 6-8 weeks old male Wistar rats into a sham operation,a model control and an NMT group,and established a CP/CPPS model in the rats by intra-prostatic injection of complete Freund adjuvant(CFA).We treated the rats in the sham operation and model control groups by injection of aseptic phosphate buffer saline(PBS)and 50 μl complete Freund adjuvant(CFA),respectively,into the ventral lobe of the prostate followed by gavage with purified water from the second day after surgery,and those in the NMT group with 50 μl CFA injected into the ventral lobe of the prostate followed by gavage with 3 ml NMT suspension at 400 mg/kg/d from the second day after surgery.After 4 weeks of treatment,we killed the animals and collected the serum and prostatic tissue samples for evaluation of the severity of prostatitis by histopathological grading of chronic prostatitis through HE staining,determination of the mRNA expressions of inflammatory factors by real-time quantita-tive PCR,measurement of the activities of related antioxidant enzymes with testing kits,and detection of the expressions of the related targets in the signaling pathways by Western blot.Results:Histopathological examination revealed different degrees of inflammatory cell infiltration in the mesenchyme,inflammatory vacuoles,irregularly shaped acini in the model control group,with a significantly higher inflammation score than in the sham operation group(P＜0.05),and reduced infiltrating lymphocytes,inflammatory vacuoles and inflammation score in the NMT group compared with those in the model controls(P＜0.05).Compared with the rats in the sham operation group,the model controls showed remarkably up-regulated expressions of IL-1 β,IL-6,IL-10,IL-17A,TNF-α and IFN-γ(P＜0.05),decreased contents of superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px)(P＜0.05),and increased content of malondialdehyde(MDA)(P＜0.05).Compared with the model controls,the rats treated with NMT exhibited markedly reduced expressions of IL-1β,IL-6,IL-10,IL-17A,TNF-α and IFN-γ(P＜0.05),increased contents of SOD,CAT and GSH-Px(P＜0.05),decreased content of MDA(P＜0.05),up-regulated expressions of nuclear factor red 2-related factor 2(n-Nrf2)and heme oxygenase-1(HO-1)(P＜0.05),and down-regulated expression of NF-κB P-P65(P＜0.05).Conclusion:NMT plays anti-oxidation and anti-inflammation roles in the pathogenesis of CP/CPPS,possibly by activation of Nrf2 and suppression of NF-κB signaling pathways.

Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
Humans ; Allergens ; Asian People ; Desensitization, Immunologic/adverse effects* ; Hypersensitivity/epidemiology* ; Retrospective Studies