OBJECTIVE To provide references for ensuring the safety of prescription preparation， dispensing， and use of parenteral nutrition solution， as well as for expanding the scope of pharmaceutical services provided by pharmacists in the Pharmacy Intravenous Admixture Services （PIVAS）. METHODS Under the guidance of PIVAS pharmacists， the rules for reviewing medical orders of parenteral nutrition in the PIVAS system and the information displayed on the infusion labels of finished parenteral nutrition solutions were refined. The process management of dispensing parenteral nutrition solution was strengthened， and detailed quality control and inspection rules were formulated. Additionally， Clinical Safety Monitoring Form for Finished Parenteral Nutrition Infusions was designed to conduct clinical monitoring and inspections for abnormalities in the finished infusions， infusion operations， and complications that may arise during the use of finished parenteral nutrition infusions. The implementation effects of the aforementioned optimization/inspection measures were evaluated by comparing data on the efficiency of medical order review for parenteral nutrition， the rate of irrational medical orders， the compliance rate of vascular access selection and infusion rate standardization， the rate of dispensing error， as well as the abnormalities occurring during clinical use， before and after the optimization/inspection initiatives were put into place. RESULTS The optimized prescription review system achieved automatic review of medical orders for parenteral nutrition， enhancing the efficiency of order review. The average time taken to review one parenteral nutrition medical order was reduced from approximately 1 minute to 10 seconds. The irrational rate of parenteral nutrition orders decreased by 31.87%. The dispensing error rate of parenteral nutrition decreased by 56.55%. The standard rate of vascular access selection and standard rate of infusion speed were increased by 13.29% and 3.54%， respectively. The PIVAS pharmacists identified and intervened in 5 abnormal cases out of 298 cases examined for use of parenteral nutrition solutions. CONCLUSIONS By optimizing the prescription review system， improving labeling information， and strengthening quality control inspections during both preparation and administration processes， PIVAS pharmacists have enhanced the safety of compounded parenteral nutrition solutions. This initiative has expanded the scope and depth of pharmaceutical care provided by dispensing pharmacists.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

In recent years, potato scab caused by Streptomyces scabies is aggravating year by year, becoming an industrial problem urgently to be resolved. Screening antagonistic bacteria with good inhibitory effect and wide adaptability is the main measure to realize effective prevention and control of the disease. This study screened three strains of antagonistic bacteria DXT2-4, T2-1 and 21-14 with good inhibitory effect on S. scabies by using plate standoff test, and identified them as Bacillus altitudinis, Bacillus safensis and Bacillus pumilus, respectively, based on morphological characteristics, physiological and biochemical properties, and 16S rRNA gene sequences. DXT2-4, T2-1 and 21-14 showed the pot control efficacy of 68.83%, 48.57%, and 57.14%, respectively. The field control efficacy of the three strains was 59.48%, 34.58% and 51.75% in Hulun Buir, Inner Mongolia Autonomous Region and 55.14%, 36.05%, and 49.05% in Huizhou, Guangdong. The three strains could grow normally in the media with pH 1.0-13.0 and with 1%-11% NaCl, and they had inhibitory effects on Rhizoctonia solani, Verticillium dahliae, Alternaria solani, and Fusarium oxysporum. The indole-3-acetic acid yields of DXT2-4, T2-1, and 21-14 were 2.23, 1.11, and 1.67 mg/L, respectively. DXT2-4 and 21-14 demonstrated strong abilities to solubilize phosphorus. The optimal carbon source, nitrogen source, and inorganic salt for fermentation of strain DXT2-4 were 2% molasses+2% corn starch, 2% soybean meal, and 0.3% MgSO₄·7H₂O, respectively. These findings suggest the three strains of bacteria can efficiently inhibit the growth of S. scabies and have strong environmental adaptability. Particularly, DXT2-4 has the best effects of inhibiting the disease and promoting plant growth, showing a high development value and broad application prospects, this is of great significance for promoting sustainable potato production and ensuring the environmentally sound utilization of resources.
Streptomyces/metabolism* ; Fermentation ; Plant Diseases/prevention & control* ; Solanum tuberosum/growth & development* ; Bacillus/growth & development* ; Antibiosis

Background Atmospheric fine particulate matter (PM_2.5) can disrupt the metabolic homeostasis of the liver and accelerate the progression of liver diseases, but there are few studies on the effects of sub-chronic PM_2.5 exposure on the liver metabolome. Objectives To investigate the effects of sub-chronic exposure to concentrated PM_2.5 on hepatic metabolomics in mice by liquid chromatography-mass spectrometry (LC-MS), and to identify potentially affected metabolites and metabolic pathways. Methods Twelve male C57BL/6J (6 weeks old) mice were randomly divided into two groups: a concentrated PM_2.5 exposure group and a clean air exposure group. The mice were exposed to concentrated PM_2.5 using the "Shanghai Meteorological and Environmental Animal Exposure System" at Fudan University. The exposure duration was 8 h per day, 6 d per week, for a total of 8 weeks. The mice's liver tissues were collected 24 h after the completion of exposure. LC-MS was performed to assess changes in the hepatic metabolome. Orthogonal partial least squares discriminant analysis and t-test were employed to identify differentially regulated metabolites between the two groups under the conditions of variable important in projection (VIP)≥1.0 and P<0.05. Metabolic pathway enrichment analysis was performed using MetaboAnalyst 5.0 software and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results A total of 297 differentially regulated metabolites were identified between the concentrated PM_2.5 exposure group and the clean air group. Among these metabolites, 142 were upregulated and 155 were downregulated. A total of 38 metabolic pathways were altered, with 7 pathways showing significant perturbation (P<0.05). These pathways involved amino acid metabolism, glucose metabolism, nucleotide metabolism, as well as cofactor and vitamin metabolism. The 7 significant metabolic pathways were pantothenic acid and coenzyme A biosynthesis; purine metabolism; amino sugar and nucleotide sugar metabolism; arginine biosynthesis; alanine, aspartate and glutamate metabolism; aminoacyl-tRNA biosynthesis; and fructose and mannose metabolism. Conclusion The results from metabolomics analysis suggest that sub-chronic exposure to PM_2.5 may disrupt hepatic energy metabolism and induce oxidative stress damage. Aspartic acid, succinic acid, ornithine, fumaric acid, as well as purine and xanthine derivatives, were identified as potential early biomarkers of hepatic response to sub-chronic PM_2.5 exposure.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Diarrhea-predominant irritable bowel syndrome(IBS-D)is a clinically common functional gastrointestinal disease,the"SCFAs-intestinal barrier"pathway plays an important role in the pathogenesis of IBS-D.Traditional Chinese medicine monomers/compounds or Chinese medicine compound can treat IBS-D by regulating the"SCFAs-intestinal barrier"through multiple pathways and multiple targets.This article takes the relationship between SCFAs and the four major intestinal barriers,as well as the mediating effect of IBS-D,as the starting point to systematically review and sort out the relevant literature on the targeted regulation of"SCFAs-intestinal barrier"in the treatment of IBS-D by Traditional Chinese medicine monomers/compounds and Chinese medicine compound;explores the theoretical basis of IBS-D caused by"SCFAs-intestinal barrier"from the perspective of"Large intes-tine dominating fluid",in order to provid ideas for Traditional Chinese medicine to establish a precision treatment system with Chinese medicine characteristics.

Objectives: This study sought to describe our institutional experience of repeated percutaneous stellate ganglion blockade (R-SGB) as a treatment option for drug-refractory electrical storm in patients with nonischemic cardiomyopathy (NICM). Methods: This prospective observational study included 8 consecutive NICM patients who had drug-refractory electrical storm and underwent R-SGB between June 1, 2021 and January 31, 2022. Lidocaine (5 ml, 1%) was injected in the vicinity of the left stellate ganglion under the guidance of ultrasound, once per day for 7 days. Data including clinical characteristics, immediate and long-term outcomes, and procedure related complications were collected. Results: The mean age was (51.5±13.6) years. All patients were male. 5 patients were diagnosed as dilated cardiomyopathy, 2 patients as arrhythmogenic right ventricular cardiomyopathy and 1 patient as hypertrophic cardiomyopathy. The left ventricular ejection fraction was 37.8%±6.6%. After the treatment of R-SGB, 6 (75%) patients were free of electrical storm. 24 hours Holter monitoring showed significant reduction in ventricular tachycardia (VT) episodes from 43.0 (13.3, 276.3) to 1.0 (0.3, 34.0) on the first day following R-SGB (P<0.05) and 0.5 (0.0, 19.3) after whole R-SGB process (P<0.05). There were no procedure-related major complications. The mean follow-up was (4.8±1.1) months, and the median time of recurrent VT was 2 months. Conclusion: Minimally invasive R-SGB is a safe and effective method to treat electrical storm in patients with NICM.
Humans ; Male ; Adult ; Middle Aged ; Aged ; Female ; Stroke Volume ; Stellate Ganglion/surgery* ; Ventricular Function, Left ; Cardiomyopathies/complications* ; Tachycardia, Ventricular/therapy* ; Treatment Outcome ; Catheter Ablation

Objective: To analyze the concentrations of glyphosate and its metabolites in occupational exposed workers and their possible effects on human health, so as to provide a reference for improving the safe use of glyphosate and toxicity research. Methods: From April to December 2020, 247 workers directly exposed to glyphosate in 5 enterprises were selected as the contact group, and 237 workers who were not exposed to glyphosate and other pesticides in the same enterprise were selected as the control group. Questionnaire survey and occupational health examination were conducted on objects, and the concentrations of glyphosate and its metabolites in the air of workplaces and biological samples were detected. The correlation between the concentrations and the difference of health examination between the two groups were analyzed. Results: The urine glyphosate concentration (0.022-47.668 mg/L), the rate of exceeding the standard (60.32%, 149/247) and the urine aminomethyl phosphonic acid concentration (<0.010-1.624 mg/L) in the contact group were higher than those in the control group [urine glyphosate concentration (<0.020-4.482 mg/L), the rate of exceeding the standard (2.53%, 6/237) and the urine aminomethyl phosphonic acid concentration (<0.010-0.524 mg/L) ], respectively (P<0.001). The exceeding standard rate of glyphosate concentration in the workplace was 33.67% (33/98). The concentration of glyphosate in the workplace was positively correlated with the concentrations of glyphosate and aminomethylphosphonic acid in urine (r(s)=0.804, 0.238, P<0.001), and the concentration of glyphosate in urine was positively correlated with the concentration of aminomethylphosphonic acid in urine (r(s)=0.549, P<0.001). The alanine aminotransferase (ALT), white cell ratio, creatinine, uric acid, the abnormal rates of ALT and total protein (TP) in the contact group were higher than those in the control group, and TP was lower than that in the control group, the differences were statistically different (P<0.05). The abnormal rates of overall liver function, overall renal function, blood routine test, urine routine test, electrocardiogram, liver B ultrasound and blood lipid in the contact group were significantly higher than those in the control group (P<0.05) . Conclusion: The concentration of glyphosate in the workplace is related to the concentrations of glyphosate and aminomethyl phosphonic acid in the urine of workers, and exposure to glyphosate may have some harmful effects on human health.
Humans ; Occupational Exposure/adverse effects* ; Health Status

Objective : To investigate the effects of gestational diabetes mellitus (GDM) on birth outcome and umbilical artery (UA) blood flow parameters in the third trimester, and to analyze the role of UA blood flow parameters in GDM and birth outcome. Methods : Based on the birth cohort from Wuhu , Anhui , China , 189 pregnant women with GDM were collected as the case group. The non⁃GDM pregnant women were matched 1 ∶ 1 according to age and pre⁃pregnancy body mass index , and 189 normal pregnant women were selected as the control group. Pregnant women with GDM were divided into poorly controlled group and well controlled group according to fasting blood glucose in the third trimester. The UA blood flow parameters and fetal birth outcomes in the third trimester were tracked. Results : Compared with the control group , UA parameters in poorly controlled and well controlled groups significantly increased (F = 6. 63 , P < 0. 05 ; F = 4. 43 , P < 0. 05 ; F = 5. 57 , P < 0. 05) . Poor glycemic control of GDM was associated with increased birth weight and risk of larger than gestational age. The multi⁃factor linear regression model showed that the Z score of the peak systolic velocity/end diastolic velocity (S/D) in the poorly controlled group was negatively correlated with birth weight (β = - 209. 78 , 95% CI: - 301. 48 - 118. 07) . S/D index Z score mediated the relationship between poor blood glucose control and birth weight. The intermediate effect value was - 58. 41 (95% CI: - 106. 40 ~ - 19. 65) , accounting for 25. 98% of the total effect. Conclusion Poor glycemic control in GDM is a risk factor for fetal weight gain , and UA function plays a partial mediating role in influencing neonatal birth weight. GDM pregnant women should strictly control blood glucose level to better protect maternal and infant health.

Actin dynamics in guard cells play a critical role in stomatal movement. Remodeling of actin arrays is triggered by different biotic and abiotic stimuli, which requires precise control. However, the molecular mechanism underlying this process is not well understood. Here we investigated whether and how the capping protein (CP) regulates actin filaments during fusicoccin (FC) -induced stomatal opening. We found that both stomatal opening and F-actin rearrangement are sensitive in the Capping Protein β-subunit (CPB) cpb-3 mutants, which resulted in its hypersensitivity to drought stress. The leaves detached from cpb-3 had a higher water loss rate (63. 45%) than from the wild type (48. 99%), and the stomatal aperture of cpb-3 was about 20% greater than in the wild type. After 1 h of FC treatment, the proportion of cpb-3 guard cells with radial actin arrays increased to 65. 5% dramatically, while only approximately 47. 2% guard cells in WT exhibited transversely oriented actin filaments. Moreover, the record of transmembrane Ca