This study was aimed at providing basic data for the control and prevention of Yersinia enterocolitica(Ye)infections.Ye isolates from stool samples collected from patients with diarrhea in a Beijing district between January 2019 and June 2024 were studied.Basic patient information and stool samples were collected,and quantitative polymerase chain reaction(qPCR)was applied to enriched cultures.Further analyses included virulence gene detection,whole-genome sequencing,and drug resistance detection.The detection rate of Ye was 0.76%(11/1 439),according to culture methods,thus yielding 12 Ye strains from distinct patients:11 isolated during the study period and 1 from 2017.The 12 Ye positive patients were 6-41 years of age,and their clinical presentations predominantly featured watery stools(66.67%,8/12)and loose stools(33.33%,4/12).The frequencies of nausea,vomiting,and fever were 41.67%(5/12),41.67%(5/12),and 8.33%(1/12),respectively.The drug resistance rates of Ye to TET,AMP,and NAL were 50.00%(6/12),33.33%(4/12),and 25.00%(3/12),respectively.One Ye strain exhibited multidrug resistance to ETP,MEM,TET,CIP,NAL,and AMP.According to qPCR detection of five common virulence genes,two Ye strains were identified as ystA+/ystB-type(ystA+/ystB-/ail+/yadA+/virF+),whereas ten strains were identified as ystA-/ystB+type(ystA-/ystB+/ail-/yadA-/virF-).VFDB database analysis based on genome sequences indicated that 12 Ye strains carried an average of 11 key virulence genes associated with adhesion,invasion,protease activity,and flagellar movement,and predicted 106 virulence genes and 12 virulence gene profiles.Only the two ystA+/ystB-Ye strains contained elements related to the TTSS and ABC transporter function.Detection of ystA-/ystB+Ye in stool isolation and culture of diarrhea cases might potentially have been missed in some cases,thus highlighting the importance of fluorescence PCR screening of fecal growth solutions to enhance isolation efficiency.Moreover,our findings revealed the genetic diversity of Ye isolated from diarrhea cases,thereby indicating the presence of multiple types of virulence genes within this pathogen.

Objective To evaluate the pharmacokinetics(PK)and pharmacodynamics(PD)of propofol injectable emulsion,and to assess the bioequivalence of test and reference formulations in healthy Chinese adult volunteers.Methods Thirty-two healthy Chinese adult volunteers were recruited and randomly assigned to a fasting.single-dose,two-period and double-crossover study.Propofol was given to eligible subjects at a speed of 30 μg·kg-1·min-1 for 30 min.The concentration of propofol in plasma was determined by avalidated high performance liquid chromatography-tandem mass spectrometery(HPLC-MS/MS)method.The PK parameters of the two preparations were calculated.Bispectral index(BIS)was measured to calculate the PD parameters of two formulations.Adverse events during the trial were recorded.Results Thirty-one volunteers were included in the pharmacokinetic parameter set.The mean values of PK parameters of test andreference formulations were as follows:Cmax were(660.87±110.25)and(683.13±125.75)ng·mL-1;AUC0-t were(473.50±86.03)and(478.40±80.25)h·ng·mL-1;AUC0-∞ were(500.45±96.49)and(507.84±88.00)h·ng·mL-1;tmax were 0.47(0.25,0.53)and 0.50(0.40,0.54)h;t1/2 were(2.97±1.74)and(3.08±1.82)h.Thirty-one volunteers were included in the bioequivalence set.The 90％confidence intervals(CI)for the geometric mean ratios of Cmax,AUC0-t,AUC0-∞ were 92.64％-101.39％,96.43％-101.00％,95.67％-100.70％,respectively.The mean values of PD parameters of test and reference formulations were as follows:BISmin were(75.94±13.66)and(74.39±12.32);BISAUC0-60minwere 5 569.85±182.78 and 5 575.68±166.19;T-BISmin were 23.00 and 29.00 min,respectively.There were no serious adverse events.Conclusion Two formulations of propofol injectable emulsion were bioequivalent and both of them exhibited good safety.

Objective To evaluate the pharmacokinetics(PK)and pharmacodynamics(PD)of propofol injectable emulsion,and to assess the bioequivalence of test and reference formulations in healthy Chinese adult volunteers.Methods Thirty-two healthy Chinese adult volunteers were recruited and randomly assigned to a fasting.single-dose,two-period and double-crossover study.Propofol was given to eligible subjects at a speed of 30 μg·kg-1·min-1 for 30 min.The concentration of propofol in plasma was determined by avalidated high performance liquid chromatography-tandem mass spectrometery(HPLC-MS/MS)method.The PK parameters of the two preparations were calculated.Bispectral index(BIS)was measured to calculate the PD parameters of two formulations.Adverse events during the trial were recorded.Results Thirty-one volunteers were included in the pharmacokinetic parameter set.The mean values of PK parameters of test andreference formulations were as follows:Cmax were(660.87±110.25)and(683.13±125.75)ng·mL-1;AUC0-t were(473.50±86.03)and(478.40±80.25)h·ng·mL-1;AUC0-∞ were(500.45±96.49)and(507.84±88.00)h·ng·mL-1;tmax were 0.47(0.25,0.53)and 0.50(0.40,0.54)h;t1/2 were(2.97±1.74)and(3.08±1.82)h.Thirty-one volunteers were included in the bioequivalence set.The 90％confidence intervals(CI)for the geometric mean ratios of Cmax,AUC0-t,AUC0-∞ were 92.64％-101.39％,96.43％-101.00％,95.67％-100.70％,respectively.The mean values of PD parameters of test and reference formulations were as follows:BISmin were(75.94±13.66)and(74.39±12.32);BISAUC0-60minwere 5 569.85±182.78 and 5 575.68±166.19;T-BISmin were 23.00 and 29.00 min,respectively.There were no serious adverse events.Conclusion Two formulations of propofol injectable emulsion were bioequivalent and both of them exhibited good safety.

This study was aimed at providing basic data for the control and prevention of Yersinia enterocolitica(Ye)infections.Ye isolates from stool samples collected from patients with diarrhea in a Beijing district between January 2019 and June 2024 were studied.Basic patient information and stool samples were collected,and quantitative polymerase chain reaction(qPCR)was applied to enriched cultures.Further analyses included virulence gene detection,whole-genome sequencing,and drug resistance detection.The detection rate of Ye was 0.76%(11/1 439),according to culture methods,thus yielding 12 Ye strains from distinct patients:11 isolated during the study period and 1 from 2017.The 12 Ye positive patients were 6-41 years of age,and their clinical presentations predominantly featured watery stools(66.67%,8/12)and loose stools(33.33%,4/12).The frequencies of nausea,vomiting,and fever were 41.67%(5/12),41.67%(5/12),and 8.33%(1/12),respectively.The drug resistance rates of Ye to TET,AMP,and NAL were 50.00%(6/12),33.33%(4/12),and 25.00%(3/12),respectively.One Ye strain exhibited multidrug resistance to ETP,MEM,TET,CIP,NAL,and AMP.According to qPCR detection of five common virulence genes,two Ye strains were identified as ystA+/ystB-type(ystA+/ystB-/ail+/yadA+/virF+),whereas ten strains were identified as ystA-/ystB+type(ystA-/ystB+/ail-/yadA-/virF-).VFDB database analysis based on genome sequences indicated that 12 Ye strains carried an average of 11 key virulence genes associated with adhesion,invasion,protease activity,and flagellar movement,and predicted 106 virulence genes and 12 virulence gene profiles.Only the two ystA+/ystB-Ye strains contained elements related to the TTSS and ABC transporter function.Detection of ystA-/ystB+Ye in stool isolation and culture of diarrhea cases might potentially have been missed in some cases,thus highlighting the importance of fluorescence PCR screening of fecal growth solutions to enhance isolation efficiency.Moreover,our findings revealed the genetic diversity of Ye isolated from diarrhea cases,thereby indicating the presence of multiple types of virulence genes within this pathogen.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

Objective:To evaluate the effect of workshop-based incontinence associated dermatitis (IAD) training course for geriatric nurse specialists, and to provide references and evidence for the application of workshop teaching model in specialized nursing training.Methods:The convenience sampling method was used to select 40 participants in the 9th Chongqing Geriatric Nurse Specialist Training Program in May 2021 as the intervention group, and IAD training was conducted using the workshop method. The 42 participants in the 8th Chongqing Geriatric Nurse Specialist Training Program in May 2020 were selected as the control group, who received IAD training through traditional teaching methods. After the training, the achievement of teaching objectives and teaching satisfaction were compared between the two groups using questionnaire survey, and IAD nursing knowledge and attitudes were compared using scales. SPSS 27.0 was used for the t-test and chi-square test. Results:The questionnaire survey showed that the intervention group achieved higher teaching objectives in all dimensions compared to the control group ( P<0.05). Compared with the control group, the intervention group had higher scores in teaching satisfaction regarding teaching format, interest in learning, practical skills, theoretical understanding, integration of theory and practice, and problem-solving abilities ( P<0.05). Compared with the control group, the intervention group demonstrated significantly higher scores in IAD nursing knowledge [(11.32±1.56) vs. (9.02±2.26), P<0.05] and attitudes [(37.63±3.54) vs. (32.81±2.97), P<0.05]. Conclusions:The workshop training has been highly recognized by the trainees, contributing to improved implementation effectiveness of teaching, enhancing the scores of IAD nursing knowledge and attitudes. This approach offers a new perspective for training with a practical focus in the specialized nursing field.

Objective: Polyethylene glycol-modified gold nanostar particles (GNS-PEG) were constructed to investigate whether the degradation of extracellular matrix in triple-negative breast cancer could improve the tumor delivery of GNS-PEG and enhance the efficacy of photothermal therapy. Methods: GNS-PEG were constructed and characterized for physicochemical properties as well as photothermal properties. At the cellular level, the cytotoxicity of halofuginone (HF) and the effect of photothermal therapy were detected. Mouse model of triple negative breast cancer was established by subcutaneous inoculation of 4T1 cells in BALB/c nude mice. Five injections of HF were given via tail vein (HF group), and tumor sections were stained with Masson stain and immunohistochemical staining for transforming growth factor β1 (TGFβ1), α-smooth muscle actin (α-SMA) and CD31 to observe the effect of tumor stromal degradation. Five injections of HF via tail vein followed by GNS-PEG (HF+ GNS-PEG group) were applied to determine the content of gold in tumor tissues by inductively coupled plasma mass spectrometry. The tumor sites of the mice in the GNS-PEG and HF+ GNS-PEG groups were irradiated with NIR laser and the temperature changes were recorded with an IR camera. The tumour growth and weight changes of mice in each group were observed. Ki-67 immunohistochemical staining, TdT-mediated dUTP nick-end labeling and HE staining were performed on tumor tissue sections from each group to observe tumor proliferation, apoptosis and necrosis. HE staining was performed on heart, liver, spleen, lung and kidney tissues from each group to observe the morphological changes of cells. Results: GNS-PEG nanoparticles showed a multi-branched structure with a particle size of 73.5±1.4 nm. The absorption peak of GNS was 810 nm, which is in the near infrared region. The photothermal conversion rate of GNS-PEG was up to 79.3%, and the photothermal effect could be controlled by the laser energy. HF has a concentration-dependent cytotoxicity, with a cell survival rate being as low as (22.8±2.6)% at HF concentration of up to 1 000 nmol/L. The photothermal effect of GNS-PEG was significant in killing tumor cells, with a cell survival rate of (32.7±5.2)% at the concentration of 25 pmol/L. The collagen area fraction, TGFβ1 integrated optical density and α-SMA integrated optical density in the tumor tissues of mice in the HF group were (2.1±0.2)%, 3.1±0.4 and 5.2±1.9, respectively, which were lower than those of the control group (all P<0.01), and the vessel diameter was 8.6±2.9 μm, which was higher than that of the control group (P<0.05). In the HF+ GNS-PEG group, the concentration of gold in tissues was 52.4 μg/g, higher than that in the GNS-PEG group (15.9 μg/g, P<0.05). After laser irradiation, the temperature of the tumor site in the HF+ GNS-PEG group was significantly higher than that in the GNS-PEG group. At the 4th minute, the temperatures of the tumor site in the GNS-PEG and HF+ GNS-PEG groups were 51.5 ℃ and 57.7 ℃ respectively; the tumor volume in the HF+ GNS-PEG group was effectively suppressed. The body weights of the mice in each group did not change significantly during the monitoring period. No significant abnormalities were observed in the main organs of the mice in the GNS-PEG group, but some hepatocytes in the HF and HF+ GNS-PEG groups showed edema and degeneration. Conclusion: The remodeling of extracellular matrix in triple-negative breast cancer could significantly improve the intratumoral delivery of GNS-PEG and thus achieve better photothermal therapy effect.
Humans ; Animals ; Mice ; Phototherapy/methods* ; Photothermal Therapy ; Triple Negative Breast Neoplasms/pathology* ; Hyperthermia, Induced/methods* ; Mice, Nude ; Gold/chemistry* ; Cell Line, Tumor

Objective: Polyethylene glycol-modified gold nanostar particles (GNS-PEG) were constructed to investigate whether the degradation of extracellular matrix in triple-negative breast cancer could improve the tumor delivery of GNS-PEG and enhance the efficacy of photothermal therapy. Methods: GNS-PEG were constructed and characterized for physicochemical properties as well as photothermal properties. At the cellular level, the cytotoxicity of halofuginone (HF) and the effect of photothermal therapy were detected. Mouse model of triple negative breast cancer was established by subcutaneous inoculation of 4T1 cells in BALB/c nude mice. Five injections of HF were given via tail vein (HF group), and tumor sections were stained with Masson stain and immunohistochemical staining for transforming growth factor β1 (TGFβ1), α-smooth muscle actin (α-SMA) and CD31 to observe the effect of tumor stromal degradation. Five injections of HF via tail vein followed by GNS-PEG (HF+ GNS-PEG group) were applied to determine the content of gold in tumor tissues by inductively coupled plasma mass spectrometry. The tumor sites of the mice in the GNS-PEG and HF+ GNS-PEG groups were irradiated with NIR laser and the temperature changes were recorded with an IR camera. The tumour growth and weight changes of mice in each group were observed. Ki-67 immunohistochemical staining, TdT-mediated dUTP nick-end labeling and HE staining were performed on tumor tissue sections from each group to observe tumor proliferation, apoptosis and necrosis. HE staining was performed on heart, liver, spleen, lung and kidney tissues from each group to observe the morphological changes of cells. Results: GNS-PEG nanoparticles showed a multi-branched structure with a particle size of 73.5±1.4 nm. The absorption peak of GNS was 810 nm, which is in the near infrared region. The photothermal conversion rate of GNS-PEG was up to 79.3%, and the photothermal effect could be controlled by the laser energy. HF has a concentration-dependent cytotoxicity, with a cell survival rate being as low as (22.8±2.6)% at HF concentration of up to 1 000 nmol/L. The photothermal effect of GNS-PEG was significant in killing tumor cells, with a cell survival rate of (32.7±5.2)% at the concentration of 25 pmol/L. The collagen area fraction, TGFβ1 integrated optical density and α-SMA integrated optical density in the tumor tissues of mice in the HF group were (2.1±0.2)%, 3.1±0.4 and 5.2±1.9, respectively, which were lower than those of the control group (all P<0.01), and the vessel diameter was 8.6±2.9 μm, which was higher than that of the control group (P<0.05). In the HF+ GNS-PEG group, the concentration of gold in tissues was 52.4 μg/g, higher than that in the GNS-PEG group (15.9 μg/g, P<0.05). After laser irradiation, the temperature of the tumor site in the HF+ GNS-PEG group was significantly higher than that in the GNS-PEG group. At the 4th minute, the temperatures of the tumor site in the GNS-PEG and HF+ GNS-PEG groups were 51.5 ℃ and 57.7 ℃ respectively; the tumor volume in the HF+ GNS-PEG group was effectively suppressed. The body weights of the mice in each group did not change significantly during the monitoring period. No significant abnormalities were observed in the main organs of the mice in the GNS-PEG group, but some hepatocytes in the HF and HF+ GNS-PEG groups showed edema and degeneration. Conclusion: The remodeling of extracellular matrix in triple-negative breast cancer could significantly improve the intratumoral delivery of GNS-PEG and thus achieve better photothermal therapy effect.
Humans ; Animals ; Mice ; Phototherapy/methods* ; Photothermal Therapy ; Triple Negative Breast Neoplasms/pathology* ; Hyperthermia, Induced/methods* ; Mice, Nude ; Gold/chemistry* ; Cell Line, Tumor

Objective:To explore the clinical effect of the modified double wing flap combined with medial plantar skin graft in the treatment of congenital syndactyly.Methods:The data of children with congenital syndactyly treated by modified double wing flap combined with medial plantar skin graft in the Department of Pediatric Orthopaedics of Xuzhou Renci Hospital from January 2019 to February 2022 were retrospectively analyzed. All of them had skin deficiency after separating syndactyly during the operation. The medial plantar was selected as the skin graft donor area. The patients were followed up through WeChat and outpatient review after operations, the contents include the shape of finger web, the shape of finger, the degree of scar contracture in the skin graft area and the medial plantar skin donor area, and the appearance of finger web was evaluated by the modified Withey correction score, and investigate the satisfaction of parents of the children.Results:A total of 10 children were included, including 5 males and 5 females, aged 1 year and 6 months to 4 years, with an average age of 2 years and 10 months. There were 8 cases of middle ring finger syndactyly, 1 case of ring little finger syndactyly, and 1 case of index middle finger syndactyly. After separating syndactyly, the skin defect area is about 1.0 cm×1.5 cm-1.5 cm×3.0 cm, and a medial plantar full-thickness skin graft with the same area is taken. The postoperative follow-up was 6-18 months, with an average of 11.3 months. All the flaps and grafts survived, and the wounds healed in primary stage. The depth, width and slope of the finger web were normal, there was no color difference between the skin graft and the surrounding skin, and the appearance of the finger was beautiful. The scar in the skin graft area and the medial plantar skin donor area was not obvious. The modified Withey correction score was 0-1, with an average of 0.1. The parents were all satisfied.Conclusion:The texture of the medial plantar skin is similar to that of the hand. After the treatment of congenital syndactyly with the modified double wing flap combined with the medial plantar skin graft, the shape of the finger web is normal, the shape of the hand is beautiful, the scar is not obvious, and the medial plantar skin donor area is hidden, which does not affect walking. After the operation, good function and shape can be obtained. It is one of the effective method to treat congenital syndactyly with insufficient skin.

Objective:To explore the clinical effect of the modified double wing flap combined with medial plantar skin graft in the treatment of congenital syndactyly.Methods:The data of children with congenital syndactyly treated by modified double wing flap combined with medial plantar skin graft in the Department of Pediatric Orthopaedics of Xuzhou Renci Hospital from January 2019 to February 2022 were retrospectively analyzed. All of them had skin deficiency after separating syndactyly during the operation. The medial plantar was selected as the skin graft donor area. The patients were followed up through WeChat and outpatient review after operations, the contents include the shape of finger web, the shape of finger, the degree of scar contracture in the skin graft area and the medial plantar skin donor area, and the appearance of finger web was evaluated by the modified Withey correction score, and investigate the satisfaction of parents of the children.Results:A total of 10 children were included, including 5 males and 5 females, aged 1 year and 6 months to 4 years, with an average age of 2 years and 10 months. There were 8 cases of middle ring finger syndactyly, 1 case of ring little finger syndactyly, and 1 case of index middle finger syndactyly. After separating syndactyly, the skin defect area is about 1.0 cm×1.5 cm-1.5 cm×3.0 cm, and a medial plantar full-thickness skin graft with the same area is taken. The postoperative follow-up was 6-18 months, with an average of 11.3 months. All the flaps and grafts survived, and the wounds healed in primary stage. The depth, width and slope of the finger web were normal, there was no color difference between the skin graft and the surrounding skin, and the appearance of the finger was beautiful. The scar in the skin graft area and the medial plantar skin donor area was not obvious. The modified Withey correction score was 0-1, with an average of 0.1. The parents were all satisfied.Conclusion:The texture of the medial plantar skin is similar to that of the hand. After the treatment of congenital syndactyly with the modified double wing flap combined with the medial plantar skin graft, the shape of the finger web is normal, the shape of the hand is beautiful, the scar is not obvious, and the medial plantar skin donor area is hidden, which does not affect walking. After the operation, good function and shape can be obtained. It is one of the effective method to treat congenital syndactyly with insufficient skin.