Objective:To explore the dosimetric advantages of 3D printed individualized molds in assisting postoperative three-dimensional brachytherapy (3D BT) for endometrial cancer.Methods:The 3D BT plans of 21 postoperative patients with early-stage endometrial cancer at the First Affiliated Hospital of Ningbo University were retrospectively selected as the individualized mold group (the mold group). On this basis, virtual single-channel cylindrical applicator plans that employed a 3D inverse simulated annealing algorithm were designed for all the patients using the Beijing Colins Planning System (the single-channel group). Comparisons were made between the two groups of plans regarding the minimum doses exposed to 90%, 98%, and 100% of target area ( D90, D98, and D100), conformity index (CI), homogeneity index (HI), and overdose index (OI), as well as the maximum doses exposed to 0.01, 1, 2, and 5 cm 3organs at risk (bladder, rectum, small intestine, and urethra) ( D0.01 cm 3, D1 cm 3, D2 cm 3, and D5 cm 3). Results:Both groups met clinical requirements. For doses to target volumes, there was no significant difference in D90, D98, and D100 between both groups, with the mold group demonstrating superior CI and HI but lower OI compared to the single-channel group ( t = -3.21, -5.99, 6.25, P < 0.05). Concerning the doses exposed to organs at risk, the mold group displayed significantly reduced D1 cm 3, D2 cm 3, and D5 cm 3 for the bladder, rectum, and urethra compared to the single-channel group ( t = 3.18, 3.21, 3.77, 7.97, 8.92, 10.92, 2.54, 3.46, 4.28, P < 0.05). There was no significant difference in the doses exposed to the small intestine between both groups ( P > 0.05) due to the large distance from the small intestine to the target volumes. Conclusions:3D printed individualized molds exhibit advantages in terms of the homogeneity and conformity indices of target volumes in postoperative three-dimensional brachytherapy for endometrial cancer, accompanied by low doses exposed to the bladder, rectum, and urethra, thereby holding the potential for broader application.

Objective:To systematically review and evaluate the predictive efficacy of various derived indicators of sequential organ failure assessment (SOFA) in mortality rate of sepsis patients.Methods:Literature on sepsis and SOFA scores were searched in PubMed, Embase and Cochrane Library. The retrieval time will be set to the time of database-building to February, 2023. The main outcome measures included 28-day mortality, 30-day mortality, in-hospital mortality, intensive care unit (ICU) mortality and long-term mortality. Literature screening, data extraction and quality evaluation were carried out independently by 2 researchers. Data were analyzed by Revman 5.3.5, Meta-disc and Stata software. Deek funnel plots were used to assess publication bias in the included studies.Results:A total of 40 articles including 51 trials were included. Of these, 32 were in English and 8 in Chinese, 17 were in prospective trials and 34 were in retrospective trials, 38 were in initial SOFA-related trials and 9 were in the change of SOFA score (ΔSOFA)-related studies, a total of 59?962 patients were enrolled. ① The area under the receiver operator characteristic curve (AUC) of initial SOFA and ΔSOFA for predicting outcome in sepsis was 0.773 and 0.787 ( Z = 0.115, P > 0.05), respectively. There was no significant difference between the two indexes in predicting the outcome of patients with sepsis. ② In subgroup analysis, due to limitations in the number of literature articles, the 28-day mortality rate and 30-day mortality rate were merged for discussion. The predictive power of ΔSOFA for 28-day or 30-day mortality was significantly higher than that of initial SOFA (AUC was 0.854, 0.787, Z = 2.603, P ≤ 0.01). ③ There were few studies onΔSOFA in predicting in-hospital mortality, ICU mortality and long-term mortality of sepsis patients. The AUC of the initial SOFA for predicting the study endpoints described above was: ICU mortality (0.814) > 28-day or 30-day mortality (0.787) > in-hospital mortality (0.697) > long-term mortality (0.646). ④ Initial SOFA and ΔSOFA in patients with sepsis of non-Han original had good predictive performance and there was no significant difference between them (AUC was 0.766, 0.811, respectively). However, the pooled sensitivity of ΔSOFA was higher (92%). ⑤ In prospective studies, initial SOFA was better at predicting outcomes in patients with sepsis (AUC was 0.804, pooled sensitivity 64%). The sensitivity of ΔSOFA indicators in predicting the outcome of sepsis patients was significantly higher than the initial SOFA (78% vs. 64%). The funnel plot showed that there was no significant publication bias in the included literature. Conclusion:ΔSOFA has a relatively high diagnostic efficacy in predicting short-term (28-day or 30-day) mortality in patients with sepsis.

Objective:To investigate the epidemiological data of maternal sepsis in intensive care unit (ICU), analyze the common causes, outcomes of maternal sepsis, and the risk factors of multi-drug resistant (MDR) bacteria.Methods:A retrospective cohort study. Maternal sepsis cases admitted to ICUs of Peking University Third Hospital, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, and Beijing Friendship Hospital Affiliated to Capital Medical University from January 2008 to September 2022 were enrolled. The following data were recorded: demographic characteristics, sequential organ failure assessment (SOFA) during infection, infection time, infection sites, invasive intervention measures before infection, microbial culture results, blood routine test during infection, body temperature, and clinical outcomes caused by infection. According to the time of sepsis occurrence, the patients were divided into pre-ICU sepsis group and ICU sepsis group, and the causes of sepsis in the two groups were analyzed. According to whether MDR occurred, the patients were divided into MDR group and non-MDR group, and clinical outcomes were analyzed. Multivariate Logistic regression was used to analyze the risk factors of MDR bacteria infection in obstetrics with sepsis.Results:160 patients were enrolled, among which 104 cases of sepsis happened before ICU and 56 cases of sepsis happened during ICU, 53 cases were with MDR bacteria and 107 cases were without MDR bacteria. The median age of the patients was 30.5 (28.0, 34.0) years old, the median temperature was 38.8 (38.2, 39.5) ℃, and the median white blood cell count (WBC) was 17.2 (13.2, 21.3)×10 9/L, the median SOFA score was 5.0 (3.0, 8.0), and 130 cases (81.2%) were referred from other hospitals. The main infection sites were uterine cavity in 64 cases (40.0%), lung in 48 cases (30.0%), abdominal and pelvic cavity in 30 cases (18.8%), urinary system in 27 cases (16.9%). Sepsis led to hysterectomy in 6 cases (3.8%), stillbirth in 8 cases (5.0%), and neonatal death in 2 cases (1.3%). The main surgical intervention measures were cesarean section (44 cases, accounting for 27.5%), followed by exploratory laparotomy (19 cases, 11.9%). The median length of ICU stay was 5.0 (3.0, 10.0) days, and the median hospital length was 14.0 (10.0, 20.8) days. Intrauterine infection was the primary cause of sepsis happened during ICU, accounting for 50.0% (28/56), of which postpartum hemorrhage accounted for 85.7% (24/28). The proportion of diabetes [28.3% (15/53) vs. 14.0% (15/107)], intrauterine operation [41.5% (22/53) vs. 23.4% (25/107)], intrauterine infection [50.9% (27/53) vs. 34.6% (37/107)] and bacteremia [18.9% (10/53) vs. 2.8% (3/107)] in the MDR group were significantly higher than those in the non-MDR group (all P < 0.05). Multivariate Logistic regression analysis showed that diabetes [odds ratio ( OR) = 2.348, 95% confidence interval (95% CI) was 1.006-5.480, P = 0.048] and intrauterine operation ( OR = 2.541, 95% CI was 1.137-5.678, P = 0.023) were independent risk factors for MDR bacterial infection in obstetrics with sepsis. Conclusions:Intrauterine infection is the common cause of maternal sepsis in ICU, and postpartum hemorrhage is the common cause of secondary intrauterine infection in ICU. MDR bacteria can lead to serious clinical outcomes. Diabetes and intrauterine operation are independent risk factors for MDR bacteria' infection.

The clinical data of 4 patients with acute eosinophilic pneumonia (AEP) diagnosed in the Department of Respiratory and Critical Care Medicine, Peking University Third Hospital were retrospectively analyzed. All 4 patients were males, aged 28, 34, 43 and 68 years respectively. The main manifestations were fever, cough and dyspnea. Three cases had a history of smoking and 1 case had a history of ulcerative colitis. The proportion of eosinophils in bronchoalveolar lavage fluid (BALF) was 85%, 93%, 41% and 50%, respectively. The proportion of eosinophils in peripheral blood was 53.3% (16.29×10 9/L), 25.1% (1.29×10 9/L), 4.8% (0.4×10 9/L) and 13.7% (1.55×10 9/L), respectively. Blood gas analysis (without supplemental oxygen) showed type I respiratory failure in 1 case, hypoxemia in 3 cases. The total IgE (normal range ≤ 100.0 KU/L) in peripheral blood of the 4 cases was>2 500.0 KU/L, 60.3 KU/L, 379.4 KU/L and 407.0 KU/L, respectively. HRCT showed diffuse distribution of lesions in both lungs, including ground glass opacity, patchy consolidation and centrilobular nodules. After diagnosis, all patients were treated with systemic glucocorticoids. Fever, cough and dyspnea, as well as the chest CT lesions were significantly improved after treatment. The patients were followed up for 29 months, 16 months, 18 months and 24 months respectively, without recurrence. AEP is a rare disease which is easy to be misdiagnosed as severe pneumonia and/or ARDS. Eosinophilia in peripheral blood is suggestive of the disease, and timely BALF cell differentials is important for early diagnosis.

Objective:To prepare the control materials of point-of-care(POC) glucose testing and evaluate their homogeneity, stability and matrix effects.Methods:The high, medium and low concentration control materials were prepared from patient leftover whole blood, which was centrifuged, fixed, washed, filtered, and aliquoted. The homogeneity and stability of the control materials were evaluated according to CNAS (China National Accreditation Service for Conformity Assessment, CNAS) GL29:2010"Reference materials-General and statistical principles for certification". The control materials were used to evaluate the matrix effects in POC glucose detection systems by Deming regression, according to the Clinical and Laboratory Standards Institute (CLSI) EP14-A3. Meanwhile, these control materials were used as the internal quality control, and their coefficients of variation ( CV) were calculated. One-way ANOVA and t-Test were used to analyze the results. Results:The homemade materials at three concentrations showed good homogeneity[ F< F0.05(9, 20)]. When the control materials were stored at 2-8 ℃, the stable phases for the opened and closed bottles were 10 days and 15 days, respectively, and there was no statistically significant difference between the results of the first day( P>0.05). The control materials at three concentrations also showed good applicability and there were no matrix effects in 10 POC glucose systems. When the control materials were detected in the internal quality control, the CVs of the high, medium and low concentrations were 0.63%, 0.66% and 1.65%, respectively, which were all below 7.5%. Conclusions:The homemade human control materials of POC glucose testing showed good homogeneity, stability and applicability. They met the requirements of quality control in hospital settings, which provided a good application prospect of the quality management of POC glucose testing.

Objective:To establish and evaluate a new real-time quality control method that can identify the random errors by using the backpropagation neural network (BPNN) algorithm and taking blood glucose test as an example.Methods:A total of 219 000 blood glucose results measured by Siemens advia 2 400 analytical system from January 2019 to July 2020 and derived from Laboratory Information System of Beijing Chaoyang Hospital Laboratory Department was regarded as the unbiased data of our study. Six deviations with different sizes were introduced to generate the corresponding biased data. With each biased data, BPNN and MovSD algorithms were used and tested, and then evaluated by traceability method and clinical method.Results:For BPNN algorithm, the block size was pre-set to 10 and the false-positive rate in all biases was within 0.1%. For MovSD, however, the optimal block size and exclusive limit were 150 and 10% separately and its false-positive rate in all biases was 0.38%, which was 0.28% higher than BPNN. Especially, for the least two error factors of 0.5 and 1, all the random errors were not detected by MovSD; for the error factor larger than 1, random errors could be detected by MovSD but the MNPed was higher than that of BPNN under all deviations. The difference was up to 91.67 times. 460 000 reference data were produced by traceability procedure. The uncertainty of BPNN algorithm evaluated by these reference data was only 0.078%.Conclusion:A real-time quality control method based on BPNN algorithm was successfully established to identify random errors in analytical phase, which was more efficient than MovSD method and provided a new idea and method for the identification of random errors in clinical practice.

Objective:To establish a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) method for the direct detection of serum M protein without antibody enrichment, and to assess its detection performance.Methods:Method establishment. A total of 712 waste serum samples were collected from patients who applied for the M protein identification test in Beijing Chaoyang Hospital affiliated to Capital Medical University. The immunoglobulin light chain was obtained by reduction of IgG and IgA by TCEP, and the detection method was preliminarily determined. The waste serum samples from 20 healthy people were collected to determine the range of mass-to-charge ratios of κ and λ light chain ions. 8 parallel tubes and 8 batches were set up for intra-and inter-batch reproducibility evaluation. 10-fold, 100-fold and 200-fold diluted M protein from 23 positive samples were detected by established MALDI-TOF MS method, and its sensitivity was evaluated. 3 methods of IFE, SPE and MALDI-TOF MS were used to detect M protein simultaneously, and the coincidence rate between MALDI-TOF MS and IFE and SPE was calculated.Results:The repeatability within and between batches was 100%, respectively. The original, 10-, 100-and 200-fold dilutions of 23 M protein-positive samples were determined, and the detection limit of MALDI-TOF MS for M protein was 0.06-0.18 g/L. IFE as the gold standard, the overall coincidence rates of SPE and MALDI-TOF MS were 85.9% and 92.3%, respectively, and the positive coincidence rates of SPE and MALDI-TOF MS were 72.8% and 99.7%, respectively, of the 712 samples. Among the different types of M-proteins, MALDI-TOF-MS agreed 100% with IFE M-protein results for IgA, IgD, IgM, free light chain type and biclonal group, while the agreements of SPE for IgM, IgA and free light chain samples were only 66.7%, 58% and 19.5%, respectively. One positive sample in the IgG group was not detected by MALDI-TOF MS. 23 M-proteins positive samples were diluted by original, 10, 100 and 200 times to access the sensitivity of MALDI-TOF MS method. The coincidence rate of MALDI-TOF MS was 100% and IFE was 96% at 10-fold dilution. The coincidence rate of IFE was 28% and 23% of MALDI-TOF MS at 100-fold and 200-fold dilution, respectively.Conclusions:A MALDI-TOF MS method for the detection of serum M-proteins was successfully established. This method has the advantages of high detection throughput, fast speed, good sensitivity, specificity and coincidence rate.

Objective:To investigate the application value of establishing the differential diagnosis model of pulmonary tuberculosis using routine laboratory data.Methods:The retrospective study was conducted. The routine laboratory data of newly diagnosed patients with pulmonary tuberculosis and other pulmonary diseases in Beijng Jishuitan Hospital and Beijing Hepingli Hospital from May 2015 to November 2021were collected. According to the random numbers showed in the computer, all the 11516 patients were divided into training dataset and test dataset with a ratio of 9∶1. Four machine learning algorithms, Support Vector Machine, Random Forest, K-Nearest Neighbor and Logistic Regression, were used to build models and select features. The diagnostic accuracy of each model was verified by using the 10-fold cross-validation method and the performance of each model was evaluated by using the receptor operator of characteristic (ROC) curve.Results:Random Forest was selected as the optimal machine learning algorithm to build the best feature model in the study. According to importance scale of factors, the differential diagnosis model of pulmonary tuberculosis consisting of 37 non-specific test indexes. In the validation set and test set the accuracy and area under curve (AUC) of the models were 0.747 and 0.736, the sensitivity, specificity and accuracy were 68.03% and 68.75%, 70.91% and 67.90%, 70.30% and 68.12%, respectively.Conclusion:A key tool in the differential diagnosis model of pulmonary tuberculosis was established by routine laboratory data in combination with machine learning. The results of this study need to be further verified by more data from medical institutions.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

Objective:To investigate the role of basic fibroblast growth factor (bFGF) in decreasing intracranial pressure in rats after intra-abdominal hypertension (IAH).Methods:A total of 60 healthy SD rats were selected for the experiment. Secondary IAH rat models were established by hemorrhagic shock/resuscitation, followed by injecting nitrogen into the peritoneal cavity of the rats to maintain an intra-abdominal pressure of 12mmHg and above. According to the random number table, the rats were divided into control group, IAH group, IAH+ bFGF group (bFGF group) and IAH+ bFGF+ PD173074 group (antagonist group), with 15 rats per group. Indicators were measured 4 hours after injury, including intracranial pressure, brain morphological observation, apparent diffusion coefficient (ADC) value, lactic acid content of brain MRI, brain water content and Evans blue exudation. Immunofluorescence staining, Western blotting and PCR were used to detect the expressions of phosphorylate-fibroblast growth factor receptor 1, 2 (p-FGFR1, 2), Zonula occludens-1 (ZO-1), β-catenin, matrix metalloproteinases 9 (MMP9), interleukin-1β (IL-1β) in brain microvascular endothelial cells (BMECs).Results:The intracranial pressure in IAH group [(5.52±0.45)mmHg] gradually increased 4 hours after injury compared control group [(3.36±0.30)mmHg]. Compared with IAH group, the intracranial pressurein bFGF group [(4.46±0.41)mmHg] was decreased ( P<0.05). Compared with bFGF group, the intracranial pressure in antagonist group [(5.36±0.44)mmHg] was enhanced ( P<0.05). Brain morphological observations in IAH group showed swelling and obvious cerebral edema, accompanied with a small amount of subarachnoid hemorrhage. Compared with IAH group, cerebral edema and brain swelling were relieved in bFGF group, while the antagonist group still showed cerebral edema and obvious brain swelling. At 4 hours after injury, MRI examination showed that the relative ADC value in IAH group (cortex: 0.82±0.11, corpus callosum: 1.26±0.17) was lower than that in control group (cortex: 1.00±0.13, corpus callosum: 1.43±0.15)( P<0.05). Compared with IAH group, the relative ADC value in bFGF group (cortex: 0.94±0.16, corpus callosum: 1.36±0.16) was increased ( P<0.05). Compared with bFGF group, the relative ADC value in antagonist group (cortex: 0.87±0.13, corpus callosum: 1.30±0.14) was decreased ( P<0.05). Relative lactic acid content in IAH group (cortex: 15.50±2.14, corpus callosum: 10.82±1.90)was higher than that in control group (cortex: 1.00±0.23, corpus callosum: 0.70±0.20)( P<0.05). Compared with IAH group, the relative lactic acid content in bFGF group (cortex: 10.85±1.42, corpus callosum: 6.96±1.30) was decreased ( P<0.05). Compared withbFGF group, the relative lactic acid content in antagonist group (cortex: 13.71±1.61, corpus callosum: 9.12±1.52) was increased ( P<0.05). The brain water content in IAH group [(87.9±0.8)%] was higher than that in control group [(76.3±0.9)%]. Compared with IAH group, the brain water content in bFGF group [(83.2±1.0)%] was decreased( P<0.05). Compared with bFGF group, the brain water content in antagonist group[(85.4±0.8)%] was increased ( P<0.05). Evans blue exudation in IAH group [(3.22±0.29)μg/ml] was greater than that in control group [(0.42±0.22)μg/ml]( P<0.05). Compared with IAH group, the Evans blue exudation in bFGF group [(2.04±0.25)μg/ml] was decreased ( P<0.05). Compared with bFGF group, the Evans blue exudation in antagonist group [(2.92±0.20)μg/ml] was increased ( P<0.05). Compared with control group, the expression of p-FGFR1 in BMECs in IAH group was weakened 4 hours after injury, but p-FGFR2 remained unchanged, the expressions of ZO-1, β-catenin protein and mRNA were weakened, and the expressions of MMP9, IL-1β protein and mRNA were enhanced ( P<0.05). Compared with IAH group, the expressions of p-FGFR1, ZO-1, β-catenin protein and mRNA were enhancedin bFGF group, and the expressions of MMP9, IL-1β protein and mRNA were weakened as well ( P<0.05). However, the expressions of p-FGFR1, ZO-1 and β-catenin protein and mRNA in antagonist group were weaker than those in bFGF group, and the expressions of MMP9 and IL-1β protein and mRNA were stronger than those in the bFGF group ( P<0.05). Conclusion:After IAH, the rat model presents damaged blood-brain barrier, increased cerebral edema, and increased intracranial pressure, and the use of bFGF can improve these symptoms. FGFR1 of BMECs is a key receptor for bFGF to play a protective role, and its receptor inhibitor PD173074 can attenuate the protective effect of bFGF.