Objective The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains is exacerbating the global burden of tuberculosis (TB), highlighting the urgent need for new treatment strategies for TB. Methods The recombinant adenovirus vaccine expressing cyclic di-adenosine monophosphate (c-di-AMP) phosphodiesterase B (CnpB) (rAd-CnpB), was administered to normal mice via mucosal immunization, either alone or in combination with drug therapy, to treat Mtb respiratory infections in mice.Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of antibodies in serum and bronchoalveolar lavage fluid (BALF). Real-time quantitative PCR was performed to assess the transcription levels of cytokines interferon γ(IFN-γ) and interleukin 10(IL-10) in mouse lungs. Flow cytometry was used to determine the proportions of CD4⁺ and CD8⁺ T cell subsets in the lungs and spleens. ELISA was employed to measure the levels of cytokines IFN-γ, IL-2, IL-10, inflammatory factors IL-6, and tumor necrosis factor α (TNF-α) secreted by spleen cells following antigen stimulation. The bacteria loads in the lungs and spleens of Mtb-infected mice were enumerated by plate counting methods. Resluts Intranasal immunization with rAd-CnpB induced high titers of IgG in mouse serum and the production of IgG and IgA in BALF, along with alterations in T lymphocyte subsets in the lungs and spleens. Administration of rAd-CnpB, either alone or in combination with drugs, to Mtb-infected mice significantly increased serum IgG levels as well as IgA and IgG levels in BALF. rAd-CnpB immunization promoted the secretion of CnpB-specific cytokines and inflammatory factors by splenocytes in Mtb-infected mice. However, rAd-CnpB immunotherapy, either alone or combined with drugs, did not significantly affect the bacterial loads in the lungs and spleens of mice with Mtb respiratory infections. Conclusion Mucosal immunization with rAd-CnpB induced significant mucosal, humoral and cellular immune responses in mice, and significantly enhanced CnpB-specific cellular immune responses in Mtb-infected mice.
Animals ; Adenoviridae/immunology* ; Mycobacterium tuberculosis/genetics* ; Mice ; Female ; Phosphoric Diester Hydrolases/genetics* ; Tuberculosis Vaccines/administration & dosage* ; Tuberculosis/prevention & control* ; Mice, Inbred BALB C ; Cytokines ; Lung/microbiology* ; Immunization ; Bronchoalveolar Lavage Fluid/immunology* ; Immunity, Mucosal

Venetoclax (Ven) is now widely used for both acute myeloid leukaemia (AML) and high-risk myelodysplastic syndrome (MDS), yet there is no consensus on salvage regimens after Ven failure. This study retrospectively evaluated the efficacy and safety of selinexor combined with subcutaneous decitabine (DAC) in 10 patients with AML or MDS with excess blasts (MDS-EB1/2) who had experienced prior Ven treatment failure. A literature review was also performed. Among the 7 patients with AML, 1 achieved complete remission (CR), 2 achieved CR with incomplete hematologic recovery (CRi), 1 achieved partial remission (PR), 2 had no remission, and 1 experienced disease progression (PD). Among the 3 patients with MDS, 2 achieved marrow CR and 1 had stable disease (SD). The median duration of response among the 6 responding patients was 2 months (range, 0.5-6 months). All 10 patients experienced varying degrees of myelosuppression. Five patients had mild gastrointestinal reactions, all of which were manageable. The overall tolerability was good, and no treatment-related deaths occurred. These findings suggest that selinexor combined with subcutaneous decitabine offers a novel and well-tolerated therapeutic option for patients with myeloid malignancies who have previously failed venetoclax-based therapy.

Venetoclax (Ven) is now widely used for both acute myeloid leukaemia (AML) and high-risk myelodysplastic syndrome (MDS), yet there is no consensus on salvage regimens after Ven failure. This study retrospectively evaluated the efficacy and safety of selinexor combined with subcutaneous decitabine (DAC) in 10 patients with AML or MDS with excess blasts (MDS-EB1/2) who had experienced prior Ven treatment failure. A literature review was also performed. Among the 7 patients with AML, 1 achieved complete remission (CR), 2 achieved CR with incomplete hematologic recovery (CRi), 1 achieved partial remission (PR), 2 had no remission, and 1 experienced disease progression (PD). Among the 3 patients with MDS, 2 achieved marrow CR and 1 had stable disease (SD). The median duration of response among the 6 responding patients was 2 months (range, 0.5-6 months). All 10 patients experienced varying degrees of myelosuppression. Five patients had mild gastrointestinal reactions, all of which were manageable. The overall tolerability was good, and no treatment-related deaths occurred. These findings suggest that selinexor combined with subcutaneous decitabine offers a novel and well-tolerated therapeutic option for patients with myeloid malignancies who have previously failed venetoclax-based therapy.

Objective:To explore the effects of human-derived fibrin glue on prevention of postoperative complications of endoscopic submucosal dissection (ESD) in early esophageal squamous cancer and precancerous lesions.Methods:A total of 210 patients with early esophageal squamous cancer or precancerous lesions who underwent ESD at Department of Gastroenterology, Zhongda Hospital Affiliated to Southeast University from April 2017 to April 2020 were included in this retrospective study. Seventy-three cases (79 esophageal lesions) where human-derived fibrin glue was used before retrieving endoscope were included in the observation group, while 137 cases (156 esophageal lesions) where fibrin glue was not used were included in the control group. The postoperative complications and pain were compared between the two groups.Results:Clinical data including general information, longitudinal length, Paris type, pathological type, invasion depth, circumferential range, area of resection, duration of operation and local steroid used were similar between the two groups ( P>0.05). The incidences of perforation, delayed bleeding and esophageal stenosis in the observation group were 2.7% (2/73), 1.4% (1/73), and 16.4% (12/73), respectively, and were 2.9% (4/137), 1.5% (2/137), and 13.1% (18/137), respectively in the control group. There were no significant differences between the two groups ( P>0.05). The incidence of postoperative pain in the observation group was 53.4% (39/73), which was significantly lower than that in the control group of 70.8% (97/137) ( χ2=6.302, P=0.012). The incidences of mild, moderate and severe pain in observation group on the day of ESD were 9.6% (7/73), 6.8% (5/73) and 5.5% (4/73), respectively, and 27.0% (37/137, χ2=8.724, P=0.003), 17.5% (24/137, χ2=4.554, P=0.033) and 0.7% (1/137, χ2=2.805, P=0.094), respectively in the control group. The incidences of mild, moderate and severe pain in the observation group on the first day after the operation were 26.0% (19/73), 5.5% (4/73) and 6.8% (5/73), respectively, and 29.2% (40/137, χ2=0.237, P=0.626), 14.6% (20/137, χ2=3.912, P=0.048) and 4.4% (6/137, χ2=0.193, P=0.660), respectively in the control group. The corresponding incidences on the second day after the operation were 5.5% (4/73), 0 and 1.4% (1/73) in the observation group and 19.0% (26/137, χ2=7.087, P=0.008), 2.9% (4/137) and 0 in the control group, respectively. Conclusion:Human-derived fibrin glue shows no obvious preventive effect on post-ESD bleeding, perforation or stenosis in early esophageal cancer and precancerous lesions. However, it can significantly reduce the incidence of ESD-related postoperative pain, especially the incidences of mild and moderate pain.

Objective To investigate the effects of dexmedetomidine on acute lung injury induced by hind limb ischemia-reperfusion in rats. Methods Sixty healthy male Wistar rats were randomly allocated into 4 groups: group C(control), group I-R(ischemia-reperfusion), group Pre-Dex(dexmedetomidine)and group Post-Dex. The morphological changes of the lung tissues were observed under light microscope , and polymorphonuclear neutrophils (PMN) in alveolar septum were counted. Meanwhile, lung coefficient, arterial partial PaO2, lung levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, interleukin (IL)-10, and malondialdehyde (MDA) were measured. Results Rats in the I-R group were resulted in the damage of the lung tissues. The rats in group Pre-Dex and group Post-Dex were featured with obvious mild lung injury. TNF-α、IL-6、IL-10 and MDA in lung levels were significantly increased in group I-R , Pre-Dex and Post-Dex. TNF-α, IL-6 and MDA in the lung were significantly decreased in group Pre-Pex and group Post-Dex. IL-10 was increased in group Pre-Dex and group Post-Dex. Conclusions Inflammatory response and oxidative stress are involved in the pathogenesis of acute lung injury induced by hind limb ischemia-reperfusion in rats. Dexmedetomidine attenuated the lung injury through anti-inflammation and anti-oxidation.

Objective To explore the types and drug resistance of pathogens in patients with type Ⅰ incision surgical site infection in orthopedics department.Methods Patients with type Ⅰ incision surgical site infection in orthopedics department at Peking University Third Hospital from January 2005 to December 2013 were retrospectively collected.Clinical characteristics of patients,distribution and drug resistance of pathogens were analyzed.Results A total of 58.2 thousands patients with type Ⅰ incision surgical site were hospitalized from January 2005 to December 2013 in orthopedics department,and among them 442 patients had infection in the type Ⅰ incision surgical site.The infection rate was 0.8％.Infection was mainly observed in elderly patients.The most common diseases were lumbar canal stenosis (21.7％),cervical spondylosis (20.6％) and lumbar intervertebral disc herniation (14.0％).A total of 453 pathogenic strains were detected,of which 52.9％ were gram-positive bacteria,45.5％ were gramnegative bacteria and 1.6 ％ were fungi.The common pathogens were Staphylococcus aureus (25.2 ％),Staphylococcus epidermidis (14.1 ％),Escherichia coli (11.5 ％),Enterobacter cloacae (7.3 ％),Pseudomonas aeruginosa (6.2 ％) and Acinetobacter baumannii (6.0 ％).The percentage of Meticillinresistant Staphylococcus aureus (MRSA) was 23.7％ and the percentage of Meticillin-resistant Staphylococcus epidermidis (MRSE) was 43.8％.Vancomycin or linezolid-resistant Staphylococcus aureus or Staphylococcus epidermidis were not detected.Proportion of extended-spectrum beta-lactamases (ESBL) producing strains in Escherichia coli was 53.8％,and proportion of ESBL-producing strains in Klebesiella pneumonia was 50.0％.The resistance rates to impenem and meropenem of the three different species in Enterobacteriaceae,including Escherichia coli,Enterobacter cloacae and Klebsiella pneumonia,were 0.Resistance rates of Pseudomonas aeruginosa to cefoperazone-sulbactam,piperacillin-tazobactam were less than 10 ％.Resistance rate of Acinetobacter baumannii to minocyline was 11.1％ and resistance rates of it to other drugs were more than 20％.Conclusions The rate of type Ⅰ incision surgical site infection in orthopedics department is low.Gram-positive and gram-negative bacteria each account for half of the pathogens.The proportion of resistant pathogens is high and empirical treatment is needed to cover these pathogens.

Objective To explore the diagnosis value of joint detection of microalbumin(mALB) ,α1-Microglolin(α1-M ) and N-acety-β-D-glucosaminidase(NAG) in the diabetes and hypertension patients with early injury of kidney .Methods Sample were col-lected from July 2013 to January 2014 ,including 63 diabetic cases(diabetic group) ,58 patients with hypertension(hypertension group) and 64 health controls(control group) ,then the levels of urinary mALB ,α1-M were detected by immunoturbidimetry ,urina-ry NAG activity was assessed by endpoint colorimetric assay .Results The levels of urinary mALB ,α1-M and NAG in diabetic group and hypertension group were higher than those in control group(P<0 .05) .The positive rates of three indices single detected were less than 50 .0% ,the positive rates of any two indices joint detected were more than 50 .0% ,the positive rate of three indices joint detected was more than 70 .0% .Conclusion The method of urinary mALB ,α1-M and NAG joint detected is sensitive and reli-able for diagnosing of the early injury of kidney .

OBJECTIVE To discuss the reasonable application of multi-enzyme abluent in the process of endoscopic cleaning and disinfecting.METHODS The multi-enzyme abluent was reasonably used to clean the endoscope in the pre-cleaning and disinfection process at thebedside,to enable it to achieve the best cleaning effect.RESULTS The reasonable application of multi-enzyme abluent could enhance the effect of endoscope cleaning to ensure the success of endoscopic disinfection.CONCLUSIONS Multi-enzyme abluent can protect the successful endoscopic disinfection and prevent the iatrogenic infection.