OBJECTIVES: To explore the association of the expression of WW domain-containing ubiquitin E3 ligase 1 (WWP1) with immune infiltration in tumor microenvironment (TME) of ovarian cancer. METHODS: Ovarian cancer patient data from The Cancer Genome Atlas (TCGA) were used to analyze the association of WWP1 expression with patient prognosis. TISCH2 was utilized to analyze the changes in immune cell subtypes in TME of metastatic tumor and after chemotherapy. The impact of WWP1 on immune cell infiltration, somatic copy number alterations of WWP1 and evolution of immune cell subtypes was evaluated using TIMER and TIGER pseudo-time analysis. A deep learning model was used to analyze TCGA pathological images to investigate the effect of WWP1 on TME of ovarian cancer. RNA-seq analysis was conducted to identify the differentially expressed genes in WWP1-overexpressing SKOV3 cells and validate immune infiltration. Multicolor immunofluorescence assay was used to analyze the immune markers in SKOV3 and SKOV3/DDP cell xenografts in nude mice. RESULTS: The patients with high WWP1 expression levels had significantly lower overall survival rate (P=0.0012). High WWP1 expression levels and Stage IV disease were both associated with a poor prognosis (P<0.05). In metastatic ovarian cancer or after chemotherapy, the percentages of malignant tumor cells and tumor-associated fibroblasts increased in the TME, accompanied by elevated WWP1 levels. WWP1 expression level was positively correlated with pro-tumorigenic immunosuppressive cells (r=0.1323-0.3955, P<0.05) and negatively with tumor-inhibiting immune cells (r=-0.1949- -0.1333, P<0.05). Specific copy number alterations of WWP1 also influenced CD8⁺ T cell percentage and neutrophil infiltration levels in the TME. RNA-seq analysis of WWP1-overexpressing SKOV3 cells and immunofluorescence assay of the tumor-bearing mice yielded findings consistent with those of bioinformatics analysis. CONCLUSIONS WWP1 may serve as a prognostic biomarker and a potential target for immune regulation in the TME of ovarian cancer.
Female ; Ovarian Neoplasms/genetics* ; Humans ; Ubiquitin-Protein Ligases/metabolism* ; Tumor Microenvironment/immunology* ; Animals ; Mice ; Cell Line, Tumor ; Mice, Nude ; Prognosis ; Gene Expression Regulation, Neoplastic

OBJECTIVE: To explore the correlation between mechanical power normalized to dynamic lung compliance (Cdyn-MP) and weaning outcomes and prognosis in mechanically ventilated patients. METHODS: A prospective, observational cohort study was conducted. Patients who underwent invasive mechanical ventilation (IMV) for more than 24 hours and used a T-tube ventilation strategy for extubation in the intensive care unit (ICU) of Lianyungang First People's Hospital and Lianyungang Second People's Hospital between January 2022 and December 2023 were enrolled. The collected data encompassed patients' baseline characteristics, primary causes of ICU admission, vital signs and laboratory indicators during the initial spontaneous breathing trial (SBT), respiratory mechanics parameters within the 4-hour period prior to the SBT, weaning outcomes and prognostic indicators. Mechanical power (MP) and Cdyn-MP were calculated using a simplified MP equation. Univariate and multivariate Logistic regression analyses were utilized to determine the independent risk factors associated with weaning failure in patients undergoing mechanical ventilation. Restricted cubic spline (RCS) analysis and Spearman rank-sum test were employed to investigate the correlation between Cdyn-MP and weaning outcomes as well as prognosis. Receiver operator characteristic curve (ROC curve) was constructed, and the area under the ROC curve (AUC) was computed to evaluate the predictive accuracy of Cdyn-MP for weaning outcomes in mechanically ventilated patients. RESULTS: A total of 366 patients undergoing IMV were enrolled in this study, with 243 cases classified as successful weaning and 123 cases classified as failed weaning. Among them, 23 patients underwent re-intubation within 48 hours after the successful withdrawal of the first SBT, non-invasive ventilation, or died. Compared with the successful weaning group, the patients in the failed weaning group had significantly increased levels of sequential organ failure assessment (SOFA) score, body temperature and respiratory rate (RR) during SBT, and respiratory mechanical parameters within the 4-hour period prior to the SBT [ventilation frequency, positive end-expiratory pressure (PEEP), platform pressure (Pplat), peak inspiratory pressure (Ppeak), dynamic driving pressure (ΔPaw), fraction of inspired oxygen (FiO₂), MP, and Cdyn-MP], dynamic lung compliance (Cdyn) was significantly reduced, and duration of IMV, ICU length of stay, and total length of hospital stay were significantly prolonged. However, there were no statistically significant differences in age, gender, body mass index (BMI), smoking history, main causes of ICU admission, other vital signs [heart rate (HR), mean arterial pressure (MAP), saturation of peripheral oxygen (SpO₂)] and laboratory indicators [white blood cell count (WBC), albumin (Alb), serum creatinine (SCr)] during SBT of patients between the two groups. Univariate Logistic regression analysis was conducted, and variables with P < 0.05 and no multicollinearity with Cdyn-MP were selected for inclusion in the multivariate Logistic regression model. The results demonstrated that SOFA score [odds ratio (OR) = 1.081, 95% confidence interval (95%CI) was 1.008-1.160, P = 0.030], and PEEP (OR = 1.191, 95%CI was 1.075-1.329, P = 0.001), FiO₂ (OR = 1.035, 95%CI was 1.006-1.068, P = 0.021) and Cdyn-MP (OR = 1.190, 95%CI was 1.086-1.309, P < 0.001) within the 4-hour period prior to the SBT were independent risk factors for weaning failure in patients undergoing IMV. The RCS analysis after adjusting for confounding factors showed that as Cdyn-MP within the 4-hour period prior to the SBT increased, the risk of weaning failure in patients undergoing IMV significantly increased (P < 0.001). The Spearman rank correlation test showed that Cdyn-MP within the 4-hour period prior to the SBT was positively correlated with respiratory mechanical parameters including ΔPaw and MP (r values were 0.773 and 0.865, both P < 0.01), and negatively correlated with Cdyn (r = -0.587, P < 0.01). Cdyn-MP within the 4-hour period prior to the SBT was positively correlated with prognostic indicators such as duration of IMV, length of ICU stay, and total length of hospital stay (r values were 0.295, 0.196, and 0.120, all P < 0.05). ROC curve analysis demonstrated that, within the 4-hour period preceding the SBT, Cdyn-MP, MP, Cdyn, and ΔPaw possessed predictive value for weaning failure in patients undergoing IMV. Notably, Cdyn-MP exhibited superior predictive capability, evidenced by an AUC of 0.761, with a 95%CI ranging from 0.712 to 0.810 (P < 0.001). At the optimal cut-off value of 408.5 J/min×cmH₂O/mL×10^-3, the sensitivity was 68.29%, and the specificity was 71.19%. CONCLUSION Cdyn-MP is related to weaning outcomes and prognosis in mechanically ventilated patients, and has good predictive ability in assessing the risk of weaning failure.
Humans ; Prospective Studies ; Ventilator Weaning ; Prognosis ; Respiration, Artificial ; Intensive Care Units ; Lung Compliance ; Female ; Male ; Middle Aged ; Aged

OBJECTIVE To screen potential adverse drug event （ADE） signals for the treatment of multiple sclerosis （MS） with ofatumumab， and to provide reference for the safe use of drugs in clinical practice. METHODS Using “ofatumumab” and the trade name “Kesimpta” as the search keywords， adverse event （AE） reports related to ofatumumab included in FDA Adverse Event Reporting System database from January 2009 to December 2023 were screened， and their reason contained the “multiple sclerosis”； ADE signal mining and analysis were conducted by reporting odds ratio method and proportional reporting ratio method. RESULTS A total of 21 759 eligible AE reports were selected， involving 62 449 AE cases； 27 system organ classes included general diseases and various reactions at the site of administration （15 021 cases）， neurological diseases （9 668 cases）， infectious and invasive diseases （5 967 cases）， injury， poisoning and surgical complications （4 952 cases）， musculoskeletal and connective tissue disorders （4 647 cases）. A total of 21 759 AE reports correspond to 606 ADE signals， including 234 ADE positive signals. A total of 107 ADE positive signals were not included in drug instruction of ofatumumab， including flu-like diseases， nasopharyngitis， cough， urinary tract infection， sore throat， insomnia， runny nose， anemia， hair loss， atrial fibrillation， and thrombocytopenia， etc. CONCLUSIONS In the process of using ofatumumab for MS， sufficient attention should be paid to ADE included in drug instructions. The ADE with strong signal strength screened in this study should also be paid special attention to， such as flu-like diseases， hemocytopenia， temperature intolerance， optic neuritis， and moyamoya disease. The increased risk of infection， cardiovascular disease， and potential damage to the respiratory and spiritual systems caused by ofatumumab can not be ignored.

ObjectiveTo evaluate the dynamic disinfection effect of the upper-room 222 nm ultraviolet radiation on the air in different areas of the emergency department, and to provide references for a new solution of air disinfection that man-machine coexisted in the medical and healthcare institutions. MethodsThe upper-room 222 nm ultraviolet radiation air sterilizers were installed at a height of 2.3‒2.6 m from the ground in the observation room, computed tomography (CT) scanning room, rescue room and consulting room of the emergency department in Beijing Tiantan Hospital, Capital Medical University . The test area was divided into a 222 nm ultraviolet group and a control group according to whether the 222 nm ultraviolet germicidal air disinfection was conducted or not. The experimental group started air disinfection at8:00 a.m., and the air sampling was conducted from 9:00 a.m. to 16:00 p.m., with a 10 min sampling interval of every 1 hour. While the control group only collected air sample with the same air sampling method used in the experimental group, without air disinfection. The air microbial sampler with six-level sieve impingement was used for the air sampling, and the differences in the total number of airborne bacterial colonies were compared between the two groups. ResultsA total of 128 air samples were collected in the trial, of which 64 were from the experimental group and 64 from the control group. The total number of airborne bacterial colonies in the experimental group was lower than that in the control group (all P<0.001), and was maintained at a lower level throughout the entire period. The killing rate of 222 nm ultraviolet radiation to airborne microorganisms was approximately 55.76% to 76.33% in different sampling areas. The qualified rates of the total number of dynamic airborne bacterial colonies in the observation room, rescue room and consulting room were improved from 12.50%, 37.50% and 25.00% to 81.25%, 100.00% and 100.00%, respectively (all P<0.001). Over 62.50% of the time, the air quality in the consulting room and CT room in the 222 nm ultraviolet group met the environment standards for airborne bacterial colony criteria of class Ⅰ or class Ⅱ. ConclusionThe upper-room222 nm ultraviolet radiation germicidal disinfection can effectively reduce the total number of airborne bacterial colonies and improve the environment for emergency department, and the continuous using of it is helpful for keeping the air safe and clean.

Ghrelin is a hormone produced by the stomach that regulates energy metabolism after acting on the central nervous system.Cocaine amphetamine-regulated transcriptional peptide(CART)neurons participate in the regulation of feeding behavior and energy balance.It is known that CART neurons are influenced by hormones to regulate energy homeostasis,but whether ghre-lin exerts its pro-appetite function by influencing CART neurons is unknown.Therefore,this study focuses on the role of VMHCART neurons in the regulation of feeding and relative body weight by ghrelin.Firstly,the whole brain expression of CART was determined by immunofluorescence.Then the effect of intraperitoneal injection of ghrelin on the expression of DMHCART neurons was evalua-ted.Finally,the ghrelin was delivered to DMH and the changes of food intake and relative body weight of mice were measured.CART immunoreactive neurons were detected in medial preoptic nucleus(MPA),arcuate nucleus(ARC),dorsomedial hypothalamic nucleus(DMH),thalamic pa-raventricular nucleus(PVT)and raphe nucleus(ROb).Compared with the control group,periph-eral injection of ghrelin significantly increased the expression of DMHC ART immunoreactive neurons(P=0.037 3).DMH long-term injection of ghrelin resulted in an increase in body weight(P=0.004 0)and feed intake(P=0.023 1).The results provide anatomical evidence for the whole brain distribution of CART,which proves that ghrelin affects feed intake and body weight of mice through CART neurons in DMH,suggesting that specific neuron types and regional specificity are involved in ghrelin regulation of feed intake and energy homeostasis.

In the context of the new era of high-quality development in public hospitals,this study aims to fully leverage the guiding role of grassroots party building in discipline development and to enhance the political function of party branches.By promoting the effectiveness of party branch work,we aim to drive the high-quality development of disciplines and the hospital as a whole.The Critical Care Medicine Department at Zhongnan Hospital of Wuhan University has actively explored innovative paths for party branch construction in conjunction with the creation of"National Model Party Branches."The initiatives focus on three areas:standard construction,integrated innovation,and social service.The department has implemented the"Soul-Casting Pro-ject,""Creative Integration Project,"and"Foundation Assistance Project,"gradually forming a distinctive party branch demon-stration brand.This approach has achieved significant results in integrating party building with business operations,fully demon-strating how high-quality party building can lead to high-quality development.

Objective:To investigate the current situation of developmental coordination disorder in preschool children in Taiyuan, providing evidence for developing health strategies for preschool children in this city.Methods:We selected 11 126 preschool children aged 3-5 years from 24 kindergartens in Taiyuan using the cluster random sampling method during November-December 2018. Each preschool child was tested with the developmental coordination disorder questionnaire for young children.Results:The incidence of developmental coordination disorder was 3.4%, and the incidence of suspected developmental coordination disorder was 5.4%, and the incidences of which were higher in boys than in girls ( χ2 = 9.46, P < 0.01). The incidence of developmental coordination disorder decreased with aging ( r = -0.06, P < 0.01). The incidence of developmental coordination disorder was negatively correlated with parents' education level and maternal passive smoking during pregnancy ( r = -0.11, P < 0.01; r = -0.12, P < 0.01; r = -0.03, P < 0.01). Lower parents' education level and maternal passive smoking during pregnancy led to a higher incidence of developmental coordination disorder in children. Conclusion:Preschool children from Taiyuan had a lower incidence of developmental coordination disorder than those from economically developed south areas. The higher the gross domestic product in the areas where the kindergartens locate, the lower the incidence of developmental coordination disorder ( r = 0.03, P < 0.01). Environmental factors have a certain impact on developmental coordination disorders in preschool children. Parents, kindergarten teachers, and child health workers should take active intervention measures against the adverse factors in the early development environment of children.

Objective:To explore the marking method for magnetically controlled capsule gastroscopy (MCCG) pictures with artificial intelligence (AI), so as to improve the work efficiency of endoscopist and to reduce the blind area of AI image reading.Methods:According to the consensus of MCCG, 24 parts of stomach in 14 775 pictures of MCCG from 35 subjects in Shenzhen Zifu Medical Technology Co., Ltd received MCCG from March to August, 2020 were marked by ten gastroenterologists and one developer of MCCG with medical background, the marking shape included rectangles and polygons. Among the ten gastroenterologists, three were senior endoscopist (the total number of gastroenteroscopy operations over 80 000, chief physician or associate chief physician), four were medium seniority endoscopist (the total number of gastroenteroscopy operations between 10 000 and 80 000, associate chief physician), and three were junior endoscopist (the total number of gastroenteroscopy operations less than 10 000, attending physician). The pictures of the same subject were pre-marked by two selected senior endoscopists with blind method, and the standard of marking with most appropriate coincidence rate was determined. The qualified marked pictures were automatically learn with AI deep learning method, and the learning results were fed back. Chi square test was used for statistical analysis.Results:According to the pre-marked results, the standard of coincidence rate for rectangular marking area was set as 50.0% and that for polygon marking area was 70.0%. The first correction for qualified rate was 39.0% (5 762/14 775). A total of 9 013 pictures were corrected. After repeated training and correction for one to five times, all pictures were qualified marked. The marking qualified rate of senior endoscopist partners was higher than that of partners of different qualifications (48.7%, 1 200/2 466 vs. 19.0%, 825/4 337), and the difference was statistically significant ( χ2=659.20, P<0.001). There was no statistically significant difference in the marking qualified rate between the senior endoscopist partners and partners of senior endoscopist and capsule developer (48.7%, 1 200/2 466 vs. 49.6%, 1 496/3 019; P>0.05). Conclusions:Establishment of AI marking method for MCCG can provide technical support for AI non-blind area reading, and AI non-blind area monitoring during the operation of MCCG.

OBJECTIVE To investigate the working pressure of return-working postpartum hospital pharmacists， analyze the influential factors， and find the suitable strategy to relieve the working pressure of postpartum pharmacists. METHODS By the means of general information questionnaire， working pressure questionnaire and self-rating depression scale， the data of postpartum pharmacists were surveyed with sampling survey to investigate the working-pressure situation. The main influential factors of the postpartum working pressure were analyzed by multiple linear stepwise regression analysis. RESULTS A total of 281 valid questionnaires were collected from 84 different hospitals， with effective rate of 88.64%. The total score of working pressure for 281 postpartum pharmacists who were back to position was （79.80±23.06） （total score of 155）. However， 51.60% of return-working postpartum pharmacists showed depressive state （≥53）. The depression status was positively correlated with working pressure. Family support， frequency of physical exercise， and ideal personnel care were all negatively associated with working pressure. CONCLUSIONS The working pressure of return-working postpartum pharmacists is at a moderate level. Depression， family support， ideal personnel care， and frequency of physical exercise are the main influential factors.

Reflux esophagitis （liver-stomach disharmony， Spittoon-Qi interties， Qi and blood stasis syndrome， turbid poison intrinsic） and nonalcoholic fatty liver disease （liver depression， spleen deficiency， phlegm and blood stasis syndrome， hot and humid embodiment， phlegmy wet resistance） and functional dyspepsia （liver depression syndrome， liver stomach with spleen deficient， spleen deficiency cold syndrome， in a word， fever） is a common disease and frequently encountered disease of digestive system. The course of disease is prolonged and the prevalence is high. The successful establishment of animal model combining disease and syndrome is the premise of exploring the mechanism of traditional Chinese medicine（TCM） effect and the foundation of the development of new preparations. At the same time， mastering the complex relationship network among disease， syndrome and prescription is the prerequisite of effective treatment. When the same syndrome occurs between different diseases， the concept of "treating different diseases with the same treatment" in TCM suggests that methods can be cross-referenced for the shortage of some syndrome models. TCM intervention of digestive diseases has the characteristics of multi-path， multi-target， multi-dimension and multi-level. Therefore， this article through the literature review， summarizes the reflux esophagitis， nonalcoholic fatty liver disease and functional dyspepsia is a common disease such as the combined operation method of the model and the intervention mechanism of TCM， so as to diseases of the digestive system of different syndrome types provides the theory basis for the objective of research， and the basic research of TCM prescription and achievements provide methodological guidance.