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 investigate the dosimetry effect of rotational errors of multi-channel cylinder vaginal applicator of intravaginal irradiation after surgery of endometrial cancer.Methods:A total of 18 patients who underwent surgery of endometrial cancer at Peking Union Medical College Hospital from June to December 2022 were selected.The plans of patients who adopted the treatment of multi-channel cylinder applicator of vagina were retrospectively analyzed,which maintained the same retained mode with clinical plan.The applicator was rotated clockwise by 22.5? and 45.0?,respectively,simulating the rotational errors that occurred in placing the applicator among clinical inter-fractions.And then,the changes of dosimetry of target area and organs at risk(OAR)under two kinds of rotation amplitudes were further analyzed.Results:When the applicator was rotated as 22.5?,the minimum doses to 90%volumes of CTV by 2.03%than that of clinical plan,which was significantly different(t=5.86,P<0.05),and the maximal doses to 2cc of OARs of bladder and rectum respectively increased 2.35%and 2.71%,and the differences of them were statistically significant(t=-3.49,-2.40,P<0.05),respectively.When the applicator was rotated as 45?,the D90 of the target area decreased by 5.75%than that of clinical plan,which was statistically significant(t=14.07,P<0.05).The D2cc values of the bladder and rectum increased respectively by 6.50%and 9.49%than that of clinical plan,which were statistically significant(t=-7.72,-6.9,P<0.05).The differences of the exposed doses of sigmoid colon and small intestine after the applicator was rotated by 22.5? and 45.0? between the plan and original plan were respectively less,which were not statistical significance.Conclusion:The multi-channel cylinder applicator can provide individualized dose distribution in intravaginal irradiation.However,attention should be paid to the placement of the applicator when patients undergo inter-fractional treatment,in order to avoid deviations in the angular alignment from the original plan.This can impact the dosages of the target area and OARs.

Objective:To describe the epidemiological distribution of hemorrhoids in a physical exami-nation population in China,which could provide evidence for precision prevention and early intervention of hemorrhoids.Methods:Chinese subjects over 18 years of age who underwent a physical examination in a nationwide chain of physical examination centers in 2018 were studied in a cross-sectional design,which collected information by a questionnaire and physical examination results from each subject.The epidemiological distribution of hemorrhoids was described using Logistic models.The gender-,age-,and region-detection rates of hemorrhoids were standardized to the Sixth National Population Census of the People's Republic of China(2010).Results:A total of 2 940 295 adult subjects were included in the study,of whom the average age was(41.7±14.0)years,and 52.6％were females.The standardized detection rate of hemorrhoids was higher for females(43.7％)than that for males(17.7％;P＜0.001)in this study.In the females,the age distribution of hemorrhoids was inverted U-shaped,with the highest standardized detection rate of hemorrhoids in the age group of 30-39 years(63.5％).In the males,the standardized detection rate of hemorrhoids increased along with age,with the highest percentage of 17.2％in the age group of 50-59 years,and the standardized detection rate of hemorrhoids in the age group of 60 and above decreased slightly(P＜0.001 for trend test).The participants with hypertension had a higher standardized detection rate of hemorrhoids than those with normal blood pressure in both males and females(P＜0.001).The standardized detection rate of hemorrhoids showed a positive corre-lation with body mass index(P＜0.001 for trend test in males).Conclusion:The detection rate of hemorrhoids varied to gender,age,obesity,and hypertension status,which could help to identify the risk factors and the high-risk sub-groups,and hence to strengthen health education and early detection accordingly,which could eventually reduce the incidence of hemorrhoids and improve the quality of life and health in the Chinese population.This study was conducted in a physical examination population,and the conclusions of this study should be extrapolated with caution.

Objective:To establish a method for obtaining planning target volume (PTV) and planning risk volume (PRV) margins caused by rotation in the use of adapt-to-position (ATP) modality of magnetic resonance linear accelerator (MRL) for patients with intracranial tumors.Methods:Clinical data of 6 patients with intracranial tumors (150 fractions in total) who received MRI-guided online ATP radiotherapy in Peking Union Medical College Hospital from November 2023 to January 2024 were retrospectively analyzed. The pre-planned CT structure was copied onto each segmented MR image and then the structures were traced back to the CT image according to the three-dimensional registration relationship. The anisotropic distance of the structure based on the original CT structure was calculated to obtain the variation range of the target and the organs at risk. The maximum anisotropic value was taken as the result of the PTV and the relationship between the results and intracranial location of different patients was analyzed. Group comparison was performed by Chi-square test. Two group comparison was conducted by post-hoc Wilcoxon signed-rank test. Results:After the rotation deviation was included, the range of target changes in the six directions of left and right (L/R), anterior and posterior (A/P) and superior and inferior (S/I) of the 6 patients were: (1.24± 0.86) mm/(1.91± 1.07) mm, (2.02± 1.26) mm/(1.66± 1.07) mm, (1.84± 1.84) mm /(2.94±1.93) mm, respectively. The results in the SI direction were significantly different, and the values in the I direction in 2 patients exceeded 4 mm, the margins suitable for all patients were 3.01 mm/2.4 mm(A/P), 1.9 mm/2.93 mm(L/R) and 3.14 mm/4.62 mm(S/I) in different directions, respectively. The L/R direction of the lens and the S/I direction of the optic nerve were significantly changed, and the A/P direction of the brain stem was (3.99± 4.64) mm. Larger values might be required when the target was in the posterior brain (left-down area, right-down area).Conclusions:The rotation deviation, organ movement and intracranial location affect the PTV and the organs at risk PRV in the MRI-guided ATP modality in intracranial tumors patients. The margin generation method based on image fusion can help to quantify the margin value reasonably.

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Humans ; Pharyngeal Neoplasms ; Esophageal Neoplasms/surgery*

Molecular pharmacognosy is a science of classification and identification, cultivation and protection, and production of active ingredients of graduated drugs at the molecular level. The proposal of molecular pharmacognosy allows the research of crude drugs to advance from the microscopic level to the genetic level. Pueraria lobata root, as a medicinal and edible plant, has high application value and economic value. There are many varieties that are easy to cause confusion, and it is not easy to distinguish and identify according to traditional identification methods. Moreover, the research of P. lobate root at the genetic level is still relatively shallow. the study received extensive attention of scholars. This article reviews recent research on molecular identification of P. lobate, transcriptome sequencing, cloning and synthesis of functional genes of P. lobate root in recent years in order to provide references for further promoting the development and utilization of P. lobate root and its active ingredients.
Pharmacognosy ; Plant Roots/genetics* ; Pueraria

Fractures, Bone ; Humans ; Ocular Motility Disorders ; Orbit ; Retrospective Studies

Animals ; Blood Glucose ; Diabetes Mellitus, Type 2/drug therapy* ; Insulin ; Insulin Resistance ; Islets of Langerhans ; Metformin/pharmacology* ; Mice ; Prediabetic State ; Sitagliptin Phosphate/pharmacology*

Objective:To compare the calculation result and analyzes the reasons for their differences so as to provide reference for the revision and improvement of the current national standards on radiation shielding design for the room of brachytherapy.Methods:For the initial activity 10 Ci (1 Ci=3.7×10 10 Bq) of radioactive sources, the shielding schemes of brachytherapy room were designed in accordance with UK Institnte of Physics and Engineering in Medicine(IPEM) Report 75, USA NCRP Report 151 and the national standard GBZ/T 201.3-2014, respectively. The differences in shielding limits, occupancy factors and other relevant factors are compared in detail. Results:The annual exposure time in a typical brachytherpy room was about 330 h. The point-specific concrete thickness were 70, 65, 61, 70, 50 cm as required by NCRP Report 151, 41, 43, 30, 40, 39 cm by IREM regulations and 84, 79, 46, 88, 39 cm by GBZ/T 201.3, respectively. The concerned concrete shielding thickness calculated under the GBZ/T 201.3-2014 was generally thicker, with lesser difference from NCRP Report 151 result, whereas that from the IPEM75 report was thinnest. The equivalent lead shielding thicknesses of the protective doors calculated using the three method are 1.170, 0.854 and 1.040 cm, respectively.Conclusions:The shielding thickness calculated using the calculation method and evaluation index recommended by the current Chinese shielding standards for brachytherapy bunker is similar to that reported in NCRP151, but is conservative. In particular, the evaluation index of instantaneous dose equivalent rate required by the current national standards and the relative conservative value of occupancy factor will significantly increase the shielding thickness required by the main shielding area.