1.Study on transmission characteristics and genetic variation of carbapenem-resistant Klebsiella pneumonia based on whole genome sequencing
Jiachen LI ; Yanying CHEN ; Yanlei GE ; Jinrui HU ; Xiaoli DU ; Jinyue LIU ; Huan XING ; Pengfang GAO ; Xiao HAN ; Yuelong LI ; Yating TANG ; Juan LI ; Zhigang CUI ; Jinhui ZHANG ; Haijian ZHOU ; Aiying DONG
Chinese Journal of Preventive Medicine 2025;59(6):892-900
Objective:To analyze the short-term hospital-based transmission characteristics and gene variation of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) by genome-wide technique to provide evidence for transmission control. Methods:The experimental strain was derived from all the CRKP isolated in Affiliated Hospital of North China University of Science and Technology from October 2022 to December 2023. Strain identification and drug susceptibility were tested with VITEK 2-Compact automatic bacterial identification drug susceptibility analyzer or disk method, and the results were interpreted through whole genome sequencing. The ST type, carbapenem resistance gene, virulence factor, and O serotype of the collected strains were analyzed.Results:Among the 115 strains of CRKP, 94 strains were isolated from the intensive care unit (ICU), accounting for 81.7%, and 21 strains were isolated from the non-intensive care unit (NICU), accounting for 18.3%. The 115 strains of CRKP can be divided into 11 ST types, of which ST11 type was the most (54.8%, 63/115), followed by ST15 type (22.6%, 26/115) and ST5492 type (15.7%, 18/115). Type ST5492 was a new clonal group in the region. The 115 strains of CRKP could be divided into 7 O serotypes, most of which were O2a type(32.2%,37/115), followed by O5 type(30.4%,35/115) and O1 type(27.8%,32/115). The resistance genes of carbapenem antibiotics showed that there were 107 strains carrying the blaKPC-2 gene, one strain with the blaNDM-1 gene, and one strain with both the blaKPC-2 and blaNDM-13 genes. Virulence genes were detected in 55 CRKP strains (47.8%, 55/115), among which six strains detected peg-344, iucA, iroB, rmpA, and rmpA2 virulence genes (5.2%, 6/115). Four virulence genes ( peg-344, iucA, rmpA, and rmpA2) were detected in 34 strains (29.6%, 34/115). Three virulence genes ( iucA, iroB and rmpA) were detected in two strains (1.7%, 2/115). Three virulence genes ( peg-344, iucA and rmpA) were detected in one strain (0.8%, 1/115). IucA and rmpA virulence genes were detected in 12 strains (10.4%, 12/115). KPC-2_ST11_O2a, KPC-2_ST15_O1 and KPC-2_ST5492_O5 were dominant clones, and their distribution was mainly in the intensive care unit. The whole genome sequence analysis showed that there were three dominant clones, among which ST11 clones were subdivided into three dominant O serotypes, all of which were mainly in the intensive care unit. Conclusion:The popular strain in the hospital of CRKP is a KPC-2_ST11 clone group carrying iucA, rmpA/rmpA2, with cross-department transmission and mutation. ST5492 is a newly-launched clone type. The intensive care unit of hvKP carrying five virulence genes, including peg-344, should be alert to the epidemic risk of CR-hvKP outbreak.
2.Genetic diversity analysis of oxacillinase in 241 clinical isolates of Pseudomonas aeruginosa
Yuelong LI ; Jingyi ZHANG ; Yubing FU ; Meiqing SUN ; Beibei MIAO ; Xinyi GONG ; Xiao HAN ; Huan XING ; Pengfang GAO ; Jiachen LI ; Yating TANG ; Xinya FAN ; Yanlei GE ; Haijian ZHOU ; Juan LI ; Aiying DONG
Chinese Journal of Preventive Medicine 2025;59(7):1004-1012
Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.
3.Natural killer cell-derived granzyme B as a therapeutic target for alleviating graft injury during liver transplantation.
Kai WANG ; Zhoucheng WANG ; Xin SHAO ; Lijun MENG ; Chuanjun LIU ; Nasha QIU ; Wenwen GE ; Yutong CHEN ; Xiao TANG ; Xiaodong WANG ; Zhengxing LIAN ; Ruhong ZHOU ; Shusen ZHENG ; Xiaohui FAN ; Xiao XU
Acta Pharmaceutica Sinica B 2025;15(10):5277-5293
Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB+ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg -/- Rag2 -/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.
4.Risk factors and their diagnostic efficacy of perioperative lower limb deep venous thrombosis in polytrauma patients with predominant severe limb trauma
Xiao YANG ; Jimin CAI ; Xin GE ; Yan WANG ; Weiya ZHOU ; Yongjun RUI
Chinese Journal of Trauma 2025;41(8):764-772
Objective:To investigate the risk factors and their diagnostic efficacy of perioperative lower limb deep vein thrombosis (DVT) in polytrauma patients with predominant severe limb trauma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 155 polytrauma patients with predominant severe trauma who were admitted to Wuxi Ninth People′s Hospital from January 2021 to December 2024, including 64 males and 91 females, aged 13-95 years [(52.1±16.9)years]. Abbreviated injury scale (AIS) was 5-15 points [(7.4±2.1)points] and injury severity score (ISS) was 17-59 points [(21.3±6.5)points]. Based on the occurrence of DVT in the perioperative period, the patients were divided into preoperative DVT group with 17 patients (11.0%) and non-preoperative DVT group with 138 patients (89.0%) as well as postoperative DVT group with 24 patients (15.5%) and non-postoperative DVT group with 131 patients (84.5%). Basic clinical data were collected, including gender, age, body mass index (BMI), underlying diseases (hypertension, diabetes mellitus), hemoglobin level (Hb), platelet count (PLT), D-dimer, ISS, trauma site [cranial and brain trauma, thoracic and abdominal trauma, upper limb trauma, lower limb trauma (femoral fracture, patellar fracture, tibial or fibular fracture, foot fracture, vascular injury), and pelvic fracture], preoperative waiting time for surgery, surgical site (pelvis and lower limb, other areas), surgical protocols (pelvic and lower limb internal fixation, external fixation of lower limb, lower limb amputation), operation duration less or more than 2 hours, amount of intraoperative blood loss, intraoperative blood transfusion requirement, venous thromboembolism (VTE) prophylaxis (pharmacological and mechanical modalities) and length of hospital stay. Univariate analysis and multivariate binary Logistic regression analysis were conducted to investigate the correlation between the aforementioned indicators and incidence of perioperative lower limb DVT in polytrauma patients with predominant severe limb trauma and determine the independent risk factors. Receiver operating characteristic (ROC) curve and area under the curve (AUC) of the relevant risk factors were analyzed to evaluate and compare the diagnostic efficacy of the risk factors for perioperative lower limb DVT in polytrauma patients with predominant severe limb trauma.Results:Univariate analysis results showed that age, history of hypertension, D-dimer, thoracic and abdominal trauma, pelvic fracture, preoperative waiting time for surgery, and length of hospital stay were significantly correlated with preoperative of DVT of the lower limbs in the patients ( P<0.05). The results of multivariate binary Logistic regression analysis showed that age ( OR=1.05, 95% CI 1.00, 1.10, P<0.05), pelvic fracture ( OR=5.03, 95% CI 1.09, 23.20, P<0.05), preoperative waiting time for surgery ( OR=1.10, 95% CI 1.00, 1.22, P<0.05) and length of hospital stay ( OR=0.89,95% CI 0.81,0.98, P<0.05) were highly correlated with preoperative DVT of the lower limbs in the patients ( P<0.05). Univariate analysis results showed that age, D-dimer, ISS, foot fracture, and length of hospital stay were significantly correlated with postoperative DVT of the lower limbs in the patients ( P<0.05). The results of multivariate binary Logistic regression analysis showed that age ( OR=1.05, 95% CI 1.01, 1.08, P<0.01), D-dimer ( OR=1.05, 95% CI 1.00, 1.10, P<0.05), ISS ( OR=1.09, 95% CI 1.01, 1.17, P<0.05), and foot fracture ( OR=3.51 , 95% CI 1.25 , 9.87 , P<0.05) were significantly correlated with postoperative DVT of the lower limbs in the patients ( P<0.05). The results of the ROC curve analysis indicated that preoperative waiting time for surgery (AUC=0.83, 95% CI 0.75, 0.91) had the highest diagnostic efficacy for preoperative DVT of the lower limbs in the patients, with the diagnostic efficacies of pelvic fracture (AUC=0.75, 95% CI 0.65, 0.85) and age (AUC=0.70, 95% CI 0.59, 0.82) decreasing successively. For postoperative DVT of the lower limbs in the patients, D-dimer (AUC=0.71, 95% CI 0.61, 0.81) exhibited the highest diagnostic efficacy, followed by age (AUC=0.70, 95% CI 0.59, 0.81), ISS (AUC=0.64, 95% CI 0.51, 0.76) and foot fracture (AUC=0.62, 95% CI 0.49, 0.74), with diagnostic efficacy decreased successively. Conclusions:For polytrauma patients with predominant severe limb trauma, age, pelvic fracture and preoperative waiting time for surgery are independent risk factors for preoperative DVT, while age, D-dimer, ISS and foot fracture are independent risk factors for postoperative DVT. Additionally, preoperative waiting time for surgery has the best diagnostic efficacy for preoperative DVT, followed by pelvic fracture and age. D-dimer has the best diagnostic efficacy for postoperative DVT, followed by age, ISS and foot fracture.
5.Study on transmission characteristics and genetic variation of carbapenem-resistant Klebsiella pneumonia based on whole genome sequencing
Jiachen LI ; Yanying CHEN ; Yanlei GE ; Jinrui HU ; Xiaoli DU ; Jinyue LIU ; Huan XING ; Pengfang GAO ; Xiao HAN ; Yuelong LI ; Yating TANG ; Juan LI ; Zhigang CUI ; Jinhui ZHANG ; Haijian ZHOU ; Aiying DONG
Chinese Journal of Preventive Medicine 2025;59(6):892-900
Objective:To analyze the short-term hospital-based transmission characteristics and gene variation of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) by genome-wide technique to provide evidence for transmission control. Methods:The experimental strain was derived from all the CRKP isolated in Affiliated Hospital of North China University of Science and Technology from October 2022 to December 2023. Strain identification and drug susceptibility were tested with VITEK 2-Compact automatic bacterial identification drug susceptibility analyzer or disk method, and the results were interpreted through whole genome sequencing. The ST type, carbapenem resistance gene, virulence factor, and O serotype of the collected strains were analyzed.Results:Among the 115 strains of CRKP, 94 strains were isolated from the intensive care unit (ICU), accounting for 81.7%, and 21 strains were isolated from the non-intensive care unit (NICU), accounting for 18.3%. The 115 strains of CRKP can be divided into 11 ST types, of which ST11 type was the most (54.8%, 63/115), followed by ST15 type (22.6%, 26/115) and ST5492 type (15.7%, 18/115). Type ST5492 was a new clonal group in the region. The 115 strains of CRKP could be divided into 7 O serotypes, most of which were O2a type(32.2%,37/115), followed by O5 type(30.4%,35/115) and O1 type(27.8%,32/115). The resistance genes of carbapenem antibiotics showed that there were 107 strains carrying the blaKPC-2 gene, one strain with the blaNDM-1 gene, and one strain with both the blaKPC-2 and blaNDM-13 genes. Virulence genes were detected in 55 CRKP strains (47.8%, 55/115), among which six strains detected peg-344, iucA, iroB, rmpA, and rmpA2 virulence genes (5.2%, 6/115). Four virulence genes ( peg-344, iucA, rmpA, and rmpA2) were detected in 34 strains (29.6%, 34/115). Three virulence genes ( iucA, iroB and rmpA) were detected in two strains (1.7%, 2/115). Three virulence genes ( peg-344, iucA and rmpA) were detected in one strain (0.8%, 1/115). IucA and rmpA virulence genes were detected in 12 strains (10.4%, 12/115). KPC-2_ST11_O2a, KPC-2_ST15_O1 and KPC-2_ST5492_O5 were dominant clones, and their distribution was mainly in the intensive care unit. The whole genome sequence analysis showed that there were three dominant clones, among which ST11 clones were subdivided into three dominant O serotypes, all of which were mainly in the intensive care unit. Conclusion:The popular strain in the hospital of CRKP is a KPC-2_ST11 clone group carrying iucA, rmpA/rmpA2, with cross-department transmission and mutation. ST5492 is a newly-launched clone type. The intensive care unit of hvKP carrying five virulence genes, including peg-344, should be alert to the epidemic risk of CR-hvKP outbreak.
6.Genetic diversity analysis of oxacillinase in 241 clinical isolates of Pseudomonas aeruginosa
Yuelong LI ; Jingyi ZHANG ; Yubing FU ; Meiqing SUN ; Beibei MIAO ; Xinyi GONG ; Xiao HAN ; Huan XING ; Pengfang GAO ; Jiachen LI ; Yating TANG ; Xinya FAN ; Yanlei GE ; Haijian ZHOU ; Juan LI ; Aiying DONG
Chinese Journal of Preventive Medicine 2025;59(7):1004-1012
Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.
7.Risk factors and their diagnostic efficacy of perioperative lower limb deep venous thrombosis in polytrauma patients with predominant severe limb trauma
Xiao YANG ; Jimin CAI ; Xin GE ; Yan WANG ; Weiya ZHOU ; Yongjun RUI
Chinese Journal of Trauma 2025;41(8):764-772
Objective:To investigate the risk factors and their diagnostic efficacy of perioperative lower limb deep vein thrombosis (DVT) in polytrauma patients with predominant severe limb trauma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 155 polytrauma patients with predominant severe trauma who were admitted to Wuxi Ninth People′s Hospital from January 2021 to December 2024, including 64 males and 91 females, aged 13-95 years [(52.1±16.9)years]. Abbreviated injury scale (AIS) was 5-15 points [(7.4±2.1)points] and injury severity score (ISS) was 17-59 points [(21.3±6.5)points]. Based on the occurrence of DVT in the perioperative period, the patients were divided into preoperative DVT group with 17 patients (11.0%) and non-preoperative DVT group with 138 patients (89.0%) as well as postoperative DVT group with 24 patients (15.5%) and non-postoperative DVT group with 131 patients (84.5%). Basic clinical data were collected, including gender, age, body mass index (BMI), underlying diseases (hypertension, diabetes mellitus), hemoglobin level (Hb), platelet count (PLT), D-dimer, ISS, trauma site [cranial and brain trauma, thoracic and abdominal trauma, upper limb trauma, lower limb trauma (femoral fracture, patellar fracture, tibial or fibular fracture, foot fracture, vascular injury), and pelvic fracture], preoperative waiting time for surgery, surgical site (pelvis and lower limb, other areas), surgical protocols (pelvic and lower limb internal fixation, external fixation of lower limb, lower limb amputation), operation duration less or more than 2 hours, amount of intraoperative blood loss, intraoperative blood transfusion requirement, venous thromboembolism (VTE) prophylaxis (pharmacological and mechanical modalities) and length of hospital stay. Univariate analysis and multivariate binary Logistic regression analysis were conducted to investigate the correlation between the aforementioned indicators and incidence of perioperative lower limb DVT in polytrauma patients with predominant severe limb trauma and determine the independent risk factors. Receiver operating characteristic (ROC) curve and area under the curve (AUC) of the relevant risk factors were analyzed to evaluate and compare the diagnostic efficacy of the risk factors for perioperative lower limb DVT in polytrauma patients with predominant severe limb trauma.Results:Univariate analysis results showed that age, history of hypertension, D-dimer, thoracic and abdominal trauma, pelvic fracture, preoperative waiting time for surgery, and length of hospital stay were significantly correlated with preoperative of DVT of the lower limbs in the patients ( P<0.05). The results of multivariate binary Logistic regression analysis showed that age ( OR=1.05, 95% CI 1.00, 1.10, P<0.05), pelvic fracture ( OR=5.03, 95% CI 1.09, 23.20, P<0.05), preoperative waiting time for surgery ( OR=1.10, 95% CI 1.00, 1.22, P<0.05) and length of hospital stay ( OR=0.89,95% CI 0.81,0.98, P<0.05) were highly correlated with preoperative DVT of the lower limbs in the patients ( P<0.05). Univariate analysis results showed that age, D-dimer, ISS, foot fracture, and length of hospital stay were significantly correlated with postoperative DVT of the lower limbs in the patients ( P<0.05). The results of multivariate binary Logistic regression analysis showed that age ( OR=1.05, 95% CI 1.01, 1.08, P<0.01), D-dimer ( OR=1.05, 95% CI 1.00, 1.10, P<0.05), ISS ( OR=1.09, 95% CI 1.01, 1.17, P<0.05), and foot fracture ( OR=3.51 , 95% CI 1.25 , 9.87 , P<0.05) were significantly correlated with postoperative DVT of the lower limbs in the patients ( P<0.05). The results of the ROC curve analysis indicated that preoperative waiting time for surgery (AUC=0.83, 95% CI 0.75, 0.91) had the highest diagnostic efficacy for preoperative DVT of the lower limbs in the patients, with the diagnostic efficacies of pelvic fracture (AUC=0.75, 95% CI 0.65, 0.85) and age (AUC=0.70, 95% CI 0.59, 0.82) decreasing successively. For postoperative DVT of the lower limbs in the patients, D-dimer (AUC=0.71, 95% CI 0.61, 0.81) exhibited the highest diagnostic efficacy, followed by age (AUC=0.70, 95% CI 0.59, 0.81), ISS (AUC=0.64, 95% CI 0.51, 0.76) and foot fracture (AUC=0.62, 95% CI 0.49, 0.74), with diagnostic efficacy decreased successively. Conclusions:For polytrauma patients with predominant severe limb trauma, age, pelvic fracture and preoperative waiting time for surgery are independent risk factors for preoperative DVT, while age, D-dimer, ISS and foot fracture are independent risk factors for postoperative DVT. Additionally, preoperative waiting time for surgery has the best diagnostic efficacy for preoperative DVT, followed by pelvic fracture and age. D-dimer has the best diagnostic efficacy for postoperative DVT, followed by age, ISS and foot fracture.
8.Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes.
Shuo ZHANG ; Hong-Jin LI ; Chun-Mei YANG ; Liu LIU ; Xiao-Ying SUN ; Jiao WANG ; Si-Ting CHEN ; Yi LU ; Man-Qi HU ; Ge YAN ; Ya-Qiong ZHOU ; Xiao MIAO ; Xin LI ; Bin LI
Chinese journal of integrative medicine 2024;30(3):222-229
OBJECTIVE:
To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.
METHODS:
Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.
RESULTS:
TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).
CONCLUSIONS
TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male
;
Animals
;
Mice
;
Tripterygium
;
Psoriasis/drug therapy*
;
Keratinocytes
;
Skin Diseases/metabolism*
;
Cytokines/metabolism*
;
Imiquimod/metabolism*
;
Dermatitis/pathology*
;
Disease Models, Animal
;
Mice, Inbred BALB C
;
Skin/metabolism*
9.Heterologous expression and product identification of diterpene synthase involved in the biosynthesis of brasilicardin A
Xiang-yu GE ; Guang-xin ZHOU ; Na XIONG ; Zi-han LU ; Xin-yu MI ; Zhi-xiang ZHU ; Xiao LIU ; Xiao-hui WANG ; Juan WANG ; She-po SHI
Acta Pharmaceutica Sinica 2024;59(7):2161-2170
Brasilicardin A, a diterpene glycoside isolated from pathogenic actinomycete
10.Analysis of drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023
Pengfang GAO ; Yanying CHEN ; Yanlei GE ; Xiaoli DU ; Huan XING ; Jiachen LI ; Yuelong LI ; Yating TANG ; Xiao HAN ; Juan LI ; Zhigang CUI ; Haijian ZHOU ; Aiying DONG
Chinese Journal of Preventive Medicine 2024;58(3):306-314
Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.

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