OBJECTIVE T o assess the in vitro antimicrobial activity of aztreonam-avibactam against metallo-β—lacta-mase(MBL)-producing carbapenem-resistant Enterobacteriaceae(CRE)using different antimicrobial susceptibility testing methods,evaluate the consistency of results based on the latest breakpoints recommended by European Committee on Antimicrobial Susceptibility Testing(EUCAST),and analyze the clinical applicability.METHODS The imipenem-or meropenem-resistant Enterobacteriaceae strains were isolated from the clinical specimens of Bei-jing Chaoyang Hospital from Jan.2019 to Mar.2023,MBL-producing CRE were selected after they were con-firmed by colloidal gold immunoassay and Sanger sequencing as the study subjects.The minimum inhibitory con-centrations(MICs)of single aztreonam and aztreonam-avibactam compounds were determined by using broth mi-crodilution method.In addition,the disk diffusion method and the gradient diffusion method were employed to further detect the in vitro susceptibility to aztreonam-avibactam.RESULTS Among the 87 strains of MBL-producing CRE that were included in the study,Escherichia coli was the most common species,accounting for 44.83％.NDM-5 was the predominant carbapenemase type,detected in 48.28％of the isolates.According to the latest EUCAST break-points,6 isolates were aztreonam-avibactam-resistant strains based on broth microdilution method,all of which were E.coli,and the resistance rate was 6.90％(6/87).However,the resistance rate that was determined by the disk diffu-sion method was significantly higher(22.99％,20/87).Among these,14 strains was within the area of technical uncer-tainty/resistant,making result interpretation difficult.In addition,the categorical agreement between the gradient diffu-sion method and the broth microdilution method reached up to 98.85％.CONCLUSIONS Aztreonam-avibactam has high antimicrobial activity against MBL-producing CRE.However,based on the latest EUCAST breakpoints,the antimicrobial susceptibility testing by the disk diffusion method results of some strains are hard to interpret.It is necessary to integrate with other methods for further validation.

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

Aim To investigate the effect of Senecio scandens Buch.-Ham on inflammatory pain mediated by mast cell P2X7 receptor.Methods Using the ATP-induced foot inflammatory pain,immunofluores-cence and toluidine blue staining techniques were used to investigate whether Senecio scandens has inhibitory effect on P2X7 receptor on mast cells.Using the calci-um ion imaging experimental technology,to explore whether Senecio scandens inhibit the intracellular cal-cium ion enrichment caused by activation of P2X7 re-ceptor on mouse peritoneal mast cell.The whole-cell patch clamp technique was used to investigate whether senecio scandens could inhibit the inward current in-duced by activation of P2X7 receptor on mouse perito-neal mast cell.Results In vivo,Senecio scandens alle-viate ATP induced inflammatory pain(3.9 g·kg-1:P＜0.05),and significantly inhibited the infiltration of P2X7 receptor-positive mast cells(3.9 g·kg-1:P＜0.05).Knockout of mast cell can reduce the analgesic effect of Senecio scandens(3.9 g·kg-1:P=0.645).In vitro.The experiment results show that senecio scandens can significantly inhibit the calcium influx(300 mg·L-1:P＜0.05;1 g·L-1:P＜0.01;3 g·L-1:P＜0.01)and the inward current mediated by P2X7 receptor in mast cell(1 g·L-1:P＜0.01).Conclusion Senecio scandens alleviate inflammatory pain by inhibiting mast cell P2X7 receptor.

Objective:To analyze the positioning error and the overall setup errors (OSEs) of patients undergoing gamma knife pain-free face mask fractionated treatment for head tumors based on kV orthogonal image guidance.Methods:A total of 58 patients who received image-guided fractionated gamma knife treatment for head tumors with a pain-free face mask at the Gamma Knife Treatment Center of Xi'an International Medical Center Hospital from July 1, 2022 to May 31, 2024 were included in the study. A kV-class orthogonal X-ray IGPS image-guided positioning system was used to collect positioning errors in three translational directions: left-right (X), anterior-posterior (Y), and head-foot (Z), as well as in three rotational directions: left-right (P), anterior-posterior (R), and head-foot ( Y) before correction. After online correction and combined with manual positioning verification, the corrected positioning errors were recalculated. The OSEs in translational and rotational directions were calculated before and after correction. The positioning errors in all six directions (X, Y, Z, P, R, Y) before and after correction were plotted. And the OSE scatter plots in translational and rotational directions were created accordingly. Errors in the six directions and OSEs in translational and rotational directions were compared. The OSEs in translational and rotational directions were analyzed across different age groups and genders. Results:The pre-correction positioning errors in the X, Y, Z, P, R, Y directions for patients were (0.45±1.54) mm, -0.96 (-1.70, -0.28) mm, 1.67 (-0.15, 3.07) mm, (0.70±1.60) °, 0.65 (0.30, 1.19) °, (0.59±0.87) °, and the post-correction positioning errors were (-0.02±0.18) mm, 0.15 (0.10, 0.21) mm, 0.06 (-0.04, 0.16) mm, (0.20±0.79) °, 0.42 (0.19, 0.78) °, (0.20±0.63) °. There were statistically significant differences between before and after correction ( t=2.30, P=0.025; Z=-5.43, P<0.001; Z=-4.10, P<0.001; t=2.56, P=0.013; Z=-3.21, P=0.001; t=3.21, P=0.002). The OSEs in translational (X, Y, Z) and rotational (P, R, Y) directions before correction were 3.07 (1.93, 4.35) mm, 1.90 (1.28, 2.66) °, and the OSEs after correction were 0.27 (0.21, 0.33) mm, 1.08 (0.70, 1.54) °, with statistically significant differences ( Z=-6.60, P<0.001; Z=-5.52, P<0.001). For patients aged 18-44 years, the OSEs in translational (X, Y, Z) and rotational (P, R, Y) directions before and after correction were 3.65 (1.62, 3.95), 0.21 (0.21, 0.31) mm, 3.25 (2.24, 3.96) °, 0.92 (0.59, 1.45) °; for patients aged 45-59 years, the OSEs were 3.57 (2.17, 5.22), 0.29 (0.22, 0.35) mm, 1.89 (1.30, 2.30) °, 1.08 (0.62, 1.51) °; for patients aged 60-74 years, the OSEs were 2.92 (1.74, 4.06), 0.24 (0.19, 0.35) mm, 2.16 (1.09, 2.95) °, 0.98 (0.78, 1.75) °; for patients aged 75-89 years, the OSEs were 3.24 (2.12, 4.37), 0.29 (0.22, 0.47) mm, 1.73 (1.01, 1.83) °, 0.60 (0.47, 1.51) °. There were no statistically significant differences in OSEs of translational and rotational directions before and after correction among the four age groups ( H=1.23, P=0.747; H=1.74, P=0.627; H=7.45, P=0.059; H=2.80, P=0.424). For male patients, the OSEs before and after correction in translational (X, Y, Z) and rotational (P, R, Y) directions were (3.19±1.59), 0.27 (0.27, 0.33) mm, 1.89 (1.27, 2.75) °, (0.84±0.59) °; for female patients, the OSEs were (3.22±1.99), 0.26 (0.25, 0.35) mm, 1.90 (1.34, 2.41) °, (1.04±0.46) °. There were no statistically significant differences in OSEs of translational and rotational directions before and after correction between genders ( t=-0.07, P=0.949; Z=-0.48, P=0.632; Z=-0.02, P=0.161; t=-2.80, P=0.424) . Conclusions:The image-guided system, which is based on the kV orthogonal X-ray stereoscopic imaging, can significantly reduce the positioning errors between fractions of pain-free face mask gamma knife treatment for head tumor patients and improve the positioning accuracy of the gamma knife through the dual verification process of "automatic correction and manual review".

OBJECTIVE T o assess the in vitro antimicrobial activity of aztreonam-avibactam against metallo-β—lacta-mase(MBL)-producing carbapenem-resistant Enterobacteriaceae(CRE)using different antimicrobial susceptibility testing methods,evaluate the consistency of results based on the latest breakpoints recommended by European Committee on Antimicrobial Susceptibility Testing(EUCAST),and analyze the clinical applicability.METHODS The imipenem-or meropenem-resistant Enterobacteriaceae strains were isolated from the clinical specimens of Bei-jing Chaoyang Hospital from Jan.2019 to Mar.2023,MBL-producing CRE were selected after they were con-firmed by colloidal gold immunoassay and Sanger sequencing as the study subjects.The minimum inhibitory con-centrations(MICs)of single aztreonam and aztreonam-avibactam compounds were determined by using broth mi-crodilution method.In addition,the disk diffusion method and the gradient diffusion method were employed to further detect the in vitro susceptibility to aztreonam-avibactam.RESULTS Among the 87 strains of MBL-producing CRE that were included in the study,Escherichia coli was the most common species,accounting for 44.83％.NDM-5 was the predominant carbapenemase type,detected in 48.28％of the isolates.According to the latest EUCAST break-points,6 isolates were aztreonam-avibactam-resistant strains based on broth microdilution method,all of which were E.coli,and the resistance rate was 6.90％(6/87).However,the resistance rate that was determined by the disk diffu-sion method was significantly higher(22.99％,20/87).Among these,14 strains was within the area of technical uncer-tainty/resistant,making result interpretation difficult.In addition,the categorical agreement between the gradient diffu-sion method and the broth microdilution method reached up to 98.85％.CONCLUSIONS Aztreonam-avibactam has high antimicrobial activity against MBL-producing CRE.However,based on the latest EUCAST breakpoints,the antimicrobial susceptibility testing by the disk diffusion method results of some strains are hard to interpret.It is necessary to integrate with other methods for further validation.

Aim To investigate the effect of Senecio scandens Buch.-Ham on inflammatory pain mediated by mast cell P2X7 receptor.Methods Using the ATP-induced foot inflammatory pain,immunofluores-cence and toluidine blue staining techniques were used to investigate whether Senecio scandens has inhibitory effect on P2X7 receptor on mast cells.Using the calci-um ion imaging experimental technology,to explore whether Senecio scandens inhibit the intracellular cal-cium ion enrichment caused by activation of P2X7 re-ceptor on mouse peritoneal mast cell.The whole-cell patch clamp technique was used to investigate whether senecio scandens could inhibit the inward current in-duced by activation of P2X7 receptor on mouse perito-neal mast cell.Results In vivo,Senecio scandens alle-viate ATP induced inflammatory pain(3.9 g·kg-1:P＜0.05),and significantly inhibited the infiltration of P2X7 receptor-positive mast cells(3.9 g·kg-1:P＜0.05).Knockout of mast cell can reduce the analgesic effect of Senecio scandens(3.9 g·kg-1:P=0.645).In vitro.The experiment results show that senecio scandens can significantly inhibit the calcium influx(300 mg·L-1:P＜0.05;1 g·L-1:P＜0.01;3 g·L-1:P＜0.01)and the inward current mediated by P2X7 receptor in mast cell(1 g·L-1:P＜0.01).Conclusion Senecio scandens alleviate inflammatory pain by inhibiting mast cell P2X7 receptor.

Objective:To explore the effects of dexmedetomidine (DEX) on postoperative pain, oxidative stress and adverse reactions in patients undergoing radical mastectomy.Methods:A total of 90 patients with breast cancer who received radical surgical treatment in our hospital from Jun. 2022 to Jun. 2023 were prospectively included as research objects and randomly divided into 3 groups with 30 patients in each group. DEX group was applied before, during and after surgery, respectively. The levels of pain visual analogue scale (VAS), Richmonation sedation score (RASS), superoxide dismu-tase (SOD) and malondialdehyde (MDA) were recorded.Results:The recovery time and extubation time in preoperative and intraoperative DEX group were significantly lower than those in postoperative DEX group, and the awakening time and extubation time in preoperative DEX group were significantly lower than those in intraoperative DEX group ( F value was 48.62 and 53.98, respectively, P<0.001). At 1 h, 6 h and 12 h after surgery, the VAS and RASS scores of patients in the preoperative and intraoperative DEX group were significantly lower than those in the postoperative DEX group, compared with those in the intraoperative DEX group. The VAS and RASS scores in the DEX group were significantly decreased ( F value: 62.34, 55.24, 69.26, 36.82, 24.20, 39.97, P<0.001). At 24h after surgery, there was no significant difference in VAS and RASS scores among the three groups ( F value was 0.45 and 0.81, respectively, P value was 0.613 and 0.418). Immediately after surgery, 24 h after surgery, 72 h after surgery, the SOD level of DEX group was significantly higher than that of DEX group before and during surgery ( F value was 29.37, 33.24, 10.35, P<0.001). MDA levels were significantly lower than those in postoperative DEX group ( F value was 30.52, 41.27, 8.26, P<0.001). There was no significant difference in the incidence of postoperative adverse reactions among all groups ( P>0.05) . Conclusion:Preoperative and intraoperative application of DEX can reduce postoperative pain and oxidative stress in breast cancer patients, help patients recover quickly after surgery, and preoperative application is superior to intraoperative application.

Objective To compare the pharmacokinetics of crushed posaconazole enteric-coated tablets and oral suspension after intragastric administration in rabbits.Methods The experiment was designed in a randomized cross-over study.Six New Zealand rabbits were intragastrically administrated with crushed posaconazole enteric-coated tablets or suspension,and blood was collected at specific time points.The concentration of posaconazole in plasma was determined by high-performance liquid chromatography,and the pharmacokinetic parameters of both groups were calculated with DAS 2.0 software.Results The main pharmacokinetic parameters of posaconazole enteric-coated tablets and suspension were obtained as follows:AUC0-twere(40.03±5.04)and(49.92±16.09)μg·mL-1·h;AUC0-∞ were(44.00±4.50)and(51.10±16.80)μg·mL-1·h;t1/2 were(7.30±1.13)and(8.53±1.34)h;Cmrx were(3.12±0.57)and(2.78±0.60)μg·mL-1;apparent volume of distribution(Vd)were(2.40±0.34)and(2.59±0.76)L·kg-1;clearance rate(CL)were(0.23±0.02)and(0.22±0.08)L·h-1·kg.There were no statistic differences in AUC0-t,Cmax and Vd between posaconazole suspension and crushed enteric-coated tablets after intragastric administration(all P＞0.05).Conclusion There was no pharmacokinetic advantage for crushed enteric-coated tablets against oral suspension.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective:To analyze the early diagnostic value of plasma soluble cluster of differentiation 14 subtype (sCD14-ST, Presepsin) in sepsis in a population with suspected sepsis in fever clinic.Methods:A prospective observational study was conducted. The patients admitted to the fever clinic of Beijing Chaoyang Hospital from April to December 2022 were enrolled as the study objects. According to sequential organ failure assessment (SOFA) score, the patients were divided into low SOFA score group (SOFA score ≤3) and high SOFA score group (SOFA score > 3). Venous blood was collected at the time of admission. The level of plasma Presepsin was detected by chemiluminescence enzyme-linked immunoassay. The level of plasma procalcitonin (PCT) was detected by enzyme-linked immunofluorescence method. The level of C-reactive protein (CRP) was detected by scattering turbidimetry. White blood cell count (WBC) and neutrophil count (NEUT) were measured by automatic blood cell analyzer. For patients with fear of cold or chills, venous blood of upper limbs was taken for blood culture at the time of admission. The differences in inflammatory biomarkers were compared between the two groups. Binary multivariate Logistic regression analysis was used to screen the early risk factors of sepsis in fever outpatients with suspected sepsis. Receiver operator characteristic curve (ROC curve) was drawn to investigate the early diagnostic value of Presepsin and other inflammatory markers in sepsis, and to analyze the optimal cut-off value.Results:A total of 149 fever outpatients with suspected sepsis were enrolled, including 92 patients with low SOFA score and 57 patients with high SOFA score. Plasma PCT and Presepsin levels in the high SOFA score group were significantly higher than those in the low SOFA score group [PCT (μg/L): 0.77 (0.18, 2.02) vs. 0.22 (0.09, 0.71), Presepsin (ng/L): 1?129.00 (785.50, 1?766.50) vs. 563.00 (460.50, 772.25), both P < 0.01]. There was no significant difference in WBC, NEUT, CRP or positive rate of blood culture between the high and low SOFA score groups [WBC (×10 9/L): 11.32±5.47 vs. 11.14±5.29, NEUT (×10 9/L): 9.88±4.89 vs. 9.60±5.10, CRP (mg/L): 54.05 (15.95, 128.90) vs. 46.11 (19.60, 104.60), blood culture positivity rate: 42.3% (11/26) vs. 29.4% (10/34), all P > 0.05]. Multivariate Logistic regression analysis showed that Presepsin was an early risk factor for sepsis in suspected sepsis patients in fever clinics [odds ratio ( OR) = 16.96, 95% confidence interval (95% CI) was 6.35-45.29, P = 0.000]. ROC curve analysis showed that the early diagnostic value of Presepsin in sepsis was significantly better than WBC, NEUT, CRP, PCT, and blood culture [the area under the ROC curve (AUC) and 95% CI: 0.832 (0.771-0.899) vs. 0.522 (0.424-0.619), 0.532 (0.435-0.629), 0.533 (0.435-0.632), 0.664 (0.574-0.753), 0.554 (0.458-0.650)]. When the optimal cut-off value of Presepsin was 646.50 ng/L, its sensitivity and positive predictive value were higher than those of WBC, NEUT, CRP, and PCT (sensitivity: 89.5% vs. 38.6%, 68.4%, 38.6%, 57.9%; positive predictive value: 64.6% vs. 44.9%, 44.3%, 47.8%, 55.9%). Conclusion:Plasma PCT and Presepsin have early diagnostic value for sepsis in suspected sepsis patients in fever clinics, and Presepsin is more sensitive than PCT and can be used as a early marker of sepsis.