OBJECTIVE To predict and verify the mechanism of Jiawei qifang weitong granule in ameliorating precancerous lesions of gastric cancer （PLGC）. METHODS Transcriptomic data of PLGC-related were obtained from the GEO database to screen differentially expressed genes and conduct functional enrichment analysis. Targets related to gastric mucosal injury repair were screened via the GeneCards database. The active ingredient targets of Jiawei qifang weitong granule were predicted using the TCMSP and other databases. The intersection of differentially expressed genes， gastric mucosal repair targets and active ingredient targets was extracted. A protein-protein interaction network was constructed based on the STRING database， and the top 6 hub target genes with the highest connectivity were screened. A PLGC rat model was established by combining 1-methyl-3-nitro-1-nitrosoguanidine with alternating fasting and full feeding. Model rats were divided into model group， weifuchun group （positive control， 0.40 g/kg）， low-， medium- and high-dose Jiawei qifang weitong granule groups （9.73， 19.44， 38.90 g/kg）， with 10 rats in each group. Another 10 unmodeled rats were set as control group. Rats in each group were intragastrically administered corresponding liquid medicine or normal saline once a day for 30 consecutive days. After the last administration， pathological morphological changes of rat gastric tissues were observed， and the mRNA expression levels of hub target genes as well as partial protein expression levels in gastric tissues were detected. RESULTS Transcriptomics and network pharmacology analyses revealed that the top 6 hub target genes ranked by connectivity included MMP9 （matrix metalloproteinase 9）， BCL2（B-cell lymphoma 2）， IL10（interleukin 10），ICAM1（intercellular adhesion molecule 1）， PTGS2 （prostaglandin-endoperoxide synthase 2）， and HIF1A （hypoxia-inducible factor 1α subunit）. Animal experiments showed that compared with the model group， gastric mucosal pathological injury was significantly alleviated in medium- and high-dose Jiawei qifang weitong granule groups and weifuchun group. The pathological injury score of gastric mucosa， the mRNA expression levels of MMP9， PTGS2， ICAM1， BCL2 and HIF1A， as well as the protein expression levels of PTGS2 and BCL2 in gastric tissues were significantly decreased （P＜0.05）， while the mRNA expression level of IL10 was significantly increased （P＜0.05）. CONCLUSIONS Jiawei qifang weitong granule may ameliorate PLGC by targeted down-regulating the mRNA expression of MMP9， PTGS2， ICAM1， BCL2 and HIF1A， up-regulating IL10 mRNA expression， and regulating the imbalance between gastric mucosal inflammatory response and injury repair.

Objective　To analyze the clinical distribution of carbapenem-resistant Enterobacter cloacae (CR-ECL) and changes in carbapenemase enzyme types in Ningbo and to provide a guide for the rational application of antibiotics in clinical practice. Methods　Clinical isolates of CR-ECL were selected in a hospital in Ningbo from 2012 to 2022. Bacterial identification and drug sensitivity testing were performed using the VITEK-2 COMPACT automated microbiology system. Strain confirmation was conducted using the VITEK MS mass spectrometry system. The presence of CR-ECL was confirmed using the E-Test method. Carbapenemase production in CR-ECL was determined using a rapid carbapenemase detection kit and polymerase chain reaction (PCR). Results　A total of 1 428 isolates of ECL were detected in a hospital in Ningbo from 2012 to 2022, of which 36 strains were CR-ECL, accounting for 2.52%. The top three sample sources of CR-ECL were sputum (52.78%), urine (19.44%), and bile (13.89%). The patients were mainly from neurosurgery wards (22.22%), general surgery (13.89%), and ICU wards (11.11%). The separation rate of CR-ECL showed no significant difference between different genders and age groups. The resistance rates of CR-ECL to ertapenem, imipenem, and meropenem were 94.44%, 58.33%, and 36.11% respectively. The resistance rates of CR-ECL to third/fourth generation cephalosporins, aztreonam, enzyme-inhibitor complexes, and quinolones were all above 69.50%, significantly higher than those of non-carbapenem-resistant Enterobacter cloacae (NCR-ECL) strains (P<0.05). For aminoglycosides, CR-ECL and NCR-ECL both maintained low resistance rates (0% and 0.22%, respectively). Among the 36 CR-ECL strains, 31 strains (86.11%) were carbapenemase producers, including three types: NDM (28 strains, 77.78%), KPC (4 strains, 11.11%), and IMP (2 strains, 5.56%). The other two carbapenemase types, OXA-48 and VIM, were not detected. The consistency rate between the rapid detection of carbapenem enzyme type and PCR detection was 100%. Conclusions　The detection rate of CR-ECL in a hospital in Ningbo showed a trend of fluctuation. CR-ECL strains are distributed across different departments and various samples of hospitals, with no differences in distribution observed between genders or age groups. Clinical isolated CR-ECL mainly produced NDM-type carbapenemases, but the enzyme types such as KPC and IMP have also emerged in recent years. The rapid identification of carbapenemase types can play an important guiding role in the clinical treatment of CR-ECL infection.

Objective To investigate the effect of"zero channel"emergency mode on the treatment of patients with severe traumatic brain injury.Methods A total of 147 patients with severe traumatic brain injury admitted to the Second Hospital of Jiaxing from January 2020 to December 2021 were selected as study objects.Sixty-two patients hospitalized in traditional emergency mode from January to December 2020 were included in control group,and 85 patients hospitalized in"zero channel"emergency mode from January to December 2021 were included in observation group.The initiation time of rescue,completion time of CT examination,completion time of blood transfusion,duration of operation,clinical prognosis and complication rate were compared between two groups.Results The initiation time of rescue,completion time of CT examination,completion time of blood transfusion,and duration of operation in observation group were significantly shorter than those in control group(P<0.05).The proportion of good recovery in observation group was significantly higher than that in control group(68.20%vs.38.70%,χ2=12.671,P<0.001).The complication rate of observation group was significantly lower than that of control group(21.18%vs.80.65%,χ2=51.000,P<0.001).Conclusion"Zero channel"emergency mode can effectively shorten the treatment time of patients with severe traumatic brain injury,improve the success rate of rescue,reduce the incidence of complications,worthy of clinical use and promotion.

OBJECTIVE Cognitive deficit is a com-mon comorbidity in temporal lobe epilepsy(TLE)and that is not well controlled by current therapeutics.Currently,how epileptic seizure affects cognitive performance remains largely unclear.The subiculum is the major out-put of the hippocampus,which projects to entorhinal cor-tex and other more distinct brain regions.Physiologically,the subiculum codes spatial working memory and naviga-tion information including place,speed,and trajectory.Importantly,prior studies have noted the importance of the subiculum in the beginning,spreading,and generaliz-ing process of hippocampal seizure.How seizure-activated neurons in subiculum participate in cognitive impairment remains largely elusive.METHODS In this study,we sought to label the subicular seizure-activated c-fos+ neu-rons with a special promoter with enhanced synaptic activity-responsive element E-SARE in the subiculum,combined with chemogenetics and designer receptors exclusively activated by designer drugs(DREADDs),Ca2+ fiber photometry approaches,and behavioral tasks,to reveal the role of these neurons in cognitive impairment in epilepsy.RESULTS We found that chemogenetic inhibi-tion of subicular seizure-tagged c-fos+ neurons(mainly CaMK Ⅱ α+ glutamatergic neurons)alleviates seizure generalization and improves cognitive performance in the hippocampal CA3 kindling TLE model.While inhibition of seizure-labeled c-fos+ GABAergic interneuron shows no effect on seizure and cognition.As a comparison,che-mogenetic inhibition of the whole subicular CaMK Ⅱ α+ neuron impairs cognitive function in na?ve mice in basal condition.Notably,inhibition of subicular seizure-tagged c-fos+ neurons enhances the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks.CONCLUSION Our results dem-onstrate that subicular seizure-activated c-fos+ neurons contribute to cognitive impairment in TLE,suggesting sei-zure-tagged c-fos+ neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.

Objective To assess the clinical value of three-dimensional hysterosalpingo-contrast sonography (3D Hy-CoSy)in patients with tubal infertility. Methods A total of 274 patients with infertility(totally 539 the fallopian tubes)from September 2011 to March 2013 in our hospital,all patients were choose 3~7 days after menstruation clean,Transvaginal three-dimensional ultrasound imaging by injecting SonoVue through the uterine tube,with dynamic obser-vation of fallopian tube in imaging mode,by adopting of transvaginal three-dimensional ultrasound imaging reconstruc-tion technology evaluate tubal patency. The result of transvaginal three-dimension ultrasound imaging among 67 cases were compared with laparoscopic Meilan hydrotubation or X-ray hysterosalpingography (HSG). Results Among 539 oviducts, 230 oviducts were diagnosed patency by HyCoSy,224 oviducts were incompletehy obstructed, and 85 oviducts were completely obstructed among which 7 were hydrosalpinx; 3 out of 274 cases were contrast medium reflux into myometrium and venous plexus nearby; The sensitivity of 3D HyCoSy was 86.67%,which compared with the re-sults of HSG and laparoscopy,specificity was 100%,positive predictive value was 96.30%, negative predictive value was 98.25%. Conclusion 3D-HyCoSy in the diagnosis of fallopian tube patency is simple, safety and effective,fully and accurately displaying the shape of uterine tube . This technique is hopeful to become an effective method to diag-nose patients with tubal infertility.

Objective To study the mechanism of glutamine dipeptide on wound healing after operations on bums. Methods Totally, 30 burned patients were randomly divided into study group and control group (15 cases in each group). All patients received parental nutrition support after operation. Study group patients were supplemented with glutamine dipeptide at a dose of 0. 5 g ·kg-1· d-1. The plasma free hydroxyproline level was measured by a standard amino acid analyzer 1 day before operation and 7 days after operation and the wound healing time was recor- ded. Results The plasma free hydroxyproline levels of both groups were higher than the normal values before opera- tion but without significant difference [control group: (2. 24±0. 84) μg/ml, study group: (2. 32±0.92) jig/ml, normal value: (1.27±0.44) μg/ml]. On the post-operative 7 day, the plasma free hydroxyproline level of study group [ (4. 31±1. 05) ng/ml] was significantly higher than that of control group [ (3. 04±1. 01) μg/ml] (P = 0.002). The wound healing time of study group [ (29. 7±5.3) d] was shorter than that of control group but with- out significant difference [ (33. 3±7.5) d, P = 0. 14 ]. Conclusion The intravenous supplementation of glutamine dipeptide may increase the plasma hydroxyproline level after operation and thus promote wound healing.

ObjectiveTo investigate the finasteride application during the off-cycle of intermittent androgen blockade (IAB) in patients with advanced prostate cancer treated with IAB.MethodsEighty-seven patients with advanced prostate cancer were divided into two groups: forty-nine patients received IAB (group A), and thirty-eight patients underwent IAB and finasteride during the off-cycle of IAB (group B). The time of treatment cycle and the time to disease progression were compared between the two groups. ResultsThe patients in group A completed 89 treatment cycles and the mean cycle length was (12.8±5.4) months [treatment time and non-treatment time were (6.6±3.5) months and (7.1±4.8) months, respectively]. The patients in group B completed 85 cycles and the mean cycle length was (15.3±5.9) months [treatment time and non-treatment time were (6.9±3.2) months and (9.2v±3.9) months, respectively]. There was a significant difference between group A and B in the mean cycle length and the non-treatment time (P=0.0428,P=0.03).The 3-year progression rate was ( 34.8±3.5 )% in group A and ( 28.4±2.7)% in groups B ( P=0.035). ConclusionsThe application of finasteride during the off-cycle of IAB in patients with advanced prostate cancer treated with intermittent androgen blockade (IAB) can delay progression of advanced prostate cancer.

OBJECTIVETo investigate the anti-human CEM lymphoma cell activities induced by TCR idiotypic DNA vaccine containing different antigen determinants in BALB/c mice.

METHODSThe specific rearranged gene fragment encoding TCRVbeta region of CEM cell line was obtained by RT-PCR technique. The PCR product was cloned into eukaryocytic expression vector pcDNA3, which was used as DNA vaccine and template for PCR amplifying different antigen determinant. Gene fragments encoding different antigen determinant were amplified and cloned into pcDNA3, separately. The experimental mice were immunized by intramuscular injection of the DNA vaccines. The specific anti-idiotype antibodies were detected by indirect immunofluorescence assay.

RESULTSTCRbetaV of CEM cell line contains five antigen determinants. Specific anti-idiotype antibody was detected in all of the six mice immunized with DNA vaccine containing all the five determinants (the highest titer was 1:480). Although the antibody could also be detected in four of the six mice immunized with DNA vaccine containing four of the five antigen determinants, the antibody titer was lower (the highest titer was 1:80). DNA vaccine containing two of the five determinants could not induce the specific antibody.

CONCLUSIONThe idiotypic DNA vaccine containing the whole TCRbetaV five antigen determinants could induce the specific anti-lymphoma idiotypic antibody in BALB/c mice.

Amino Acid Sequence ; Animals ; Antibodies, Anti-Idiotypic ; blood ; immunology ; Base Sequence ; Complementarity Determining Regions ; genetics ; immunology ; Epitopes ; genetics ; immunology ; HL-60 Cells ; Humans ; Lymphoma ; immunology ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Receptors, Antigen, T-Cell, alpha-beta ; genetics ; immunology ; Sequence Analysis, DNA ; Tumor Cells, Cultured ; Vaccines, DNA ; genetics ; immunology

This study was undertaken to investigate the anti-lymphocytic malignacy immunologic effects induced by TCR idiotypic DNA vaccine on BALB/c mice. CEM lymphoma cell line and BALB/c mice were used as models. The rearrangement gene fragment coding TCR Vbeta region of CEM cell line was obtained by RT-PCR technique. The PCR product was cloned into the eukaryocytic expression vector pcDNA3 to be used as DNA vaccine. The experimental animals were immunized by intramuscular injection with DNA vaccine. The specific anti-idiotypic antibody was detected by indirect immunofluorescence assay. The specific anti-idiotypic cellular immunity was detected by CTL activity assay using MTT method. The results showed that specific anti-idiotypic antibody in the immunized mice sera could be found since four weeks after immunization and came to the peak of titer on the sixth week. Using IL-6 as immunological adjuvant could significantly increase the antibody titers. It was concluded that the TCR idiotypic DNA vaccine could induce effectively the specific anti-lymphoma idiotypic antibody in BALB/c mice. Using IL-6 as immunological adjuvant could significantly increase the antibody titers induced by idiotipic DNA vaccine.