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.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Intravascular large B-cell lymphoma(IVLBCL)is an aggressive extranodal large B-cell lymphoma,cocurrence in the same organ with other malignancies is very rare,especially in the lung.Here,we report a rare case of lung adenocarcinoma with IVLBCL.The patient was admitted to the hospital due to diarrhea associated with fever and cough.A computed tomography(CT)scan of the chest showed an irregular patchy high-density shadow in the upper lobe of the right lung with ground-glass opacity at the margin.After admission,the patient was given anti-infection treatment,but still had inter-mittent low fever(up to 37.5 oC).The pathological diagnosis of percutaneous lung biopsy(PLB)was lepidic-predominant ad-enocarcinoma with local infiltration,which was proved to be invasive nonmucinous adenocarcinoma of the lung with IVLBCL after surgery.This paper analyzed the clinicopathological characteristics and reviewed the relevant literature to improve the knowledge of clinicians and pathologists and avoid missed diagnosis or misdiagnosis.

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.

Objective:To construct a novel cuproptosis-related gene signature (CRGS) for prediction of prognosis, immunotherapy response and drug sensitivity in patients with hepatocellular carcinoma (HCC).Methods:Data materials for this study were obtained from the international cancer genome consortium (ICGC), the cancer genome atlas (TCGA) database and Migort210 database, and protein expression profiles were obtained from the human protein atlas image classification database. Based on the TCGA cohort, the least absolute shrinkage and selection operator algorithm was applied to construct the CRGS and calculate the risk score for each HCC patient. HCC patients were grouped according to the median risk score: HCC patients in the TCGA cohort were divided into a high-risk group TCGA and a low-risk group TCGA with 184 cases in each group; HCC patients in the ICGC cohort were divided into a high-risk group ICGC and a low-risk group ICGC with 116 cases in each group. Patients in the Migort210 cohort were divided into a responder group ( n=68) and a non-responder group ( n=230) based on their response to immunotherapy. We assessed the value of CRGS in predicting the prognosis of HCC patients in the TCGA cohort and validated whether CRGS could be used to predict the prognosis of HCC patients in the ICGC dataset. To explore the role of CRGS in predicting immunotherapy response and drug sensitivity in HCC patients based on data from the TCGA cohort, and to apply the Migort210 immunotherapy cohort to validate the clinical value of CRGS in predicting immunotherapy in malignant tumors. Results:CRGS consists of four copper death-related genes: GLS, CDKN2A, LIPT1, and DLAT. Patients in the high-risk group TCGA had lower overall survival (OS), disease-specifical survival, and progression-free interval than those in the low-risk group TCGA (all P<0.01). OS of patients in the high-risk group ICGC was lower than that in the low-risk group ICGC ( P=0.022). Multivariate Cox regression analysis showed that CRGS was an independent risk factor for poor prognosis in HCC patients (TCGA: HR=2.991, 95% CI: 1.781-5.049, P<0.001; ICGC: HR=4.621, 95% CI: 1.685-12.674, P=0.033). Risk scores were positively correlated with the expression levels of CTLA4, PDCD1, CD80 and HLLA2 (all P<0.001). Patients in the high-risk group TCGA had lower tumor immune dysfunction and rejection scores than those in the low-risk group TCGA [-0.04(-0.07, -0.02) vs. -0.02(-0.04, 0) points], and the difference was statistically significant ( P<0.001). Patients in the responder group had a higher risk score than the non-responder group [1.70 (1.56, 1.90) vs. 1.63 (1.52, 1.80)], with a statistically significant difference ( P<0.05). The half-inhibitory concentrations (IC 50) for sunitinib, rapamycin and etanercept were higher in the high-risk group TCGA than that in the low-risk group TCGA, while the IC 50 for erlotinib was lower than that in the low-risk group TCGA, and the differences were all statistically significant (all P<0.001). Conclusion:The CRGS might be served as a potential biomarker to predict the prognoses, immunotherapy response, and drug sensitivity of patients with HCC.

Objective:To compare results of four glycosylated hemoglobin A1c (HbA1c) detection methods and to evaluate the uncertainty of HbA1C results in clinical laboratory, and to provide method for clinical laboratory on the evaluation of uncertainty.Methods:According to the four uncertainty evaluation methods, which were recommended by "CNAS-TRL-001, the evaluation and expression of measurement uncertainty in medical laboratory", the relative and absolute uncertainty of low, medium and high HbA1c in 33 clinical laboratories measured in 2019 and 35 clinical laboratories measured in 2020 was evaluated by more than 6 months of internal quality control (IQC) data, trueness verification and external quality assessment (EQA) data. The four uncertainty evaluation methods were: IQC data and trueness verification data (method 1), only trueness verification data (method 2), IQC and EQA data (method 3) and only EQA data (method 4). The related statistical methods used in this analysis were Friedman and Wilcoxon signed rank test.Results:For method 1, the median range of relative and absolute uncertainty of low, medium and high HbA1c detection in 2019 and 2020 ranged from 4.21% to 9.24% and from 0.27% to 0.64%, respectively. Compared to method 1, the relative and absolute uncertainties obtained by method 2 were smaller, and the differences were statistically significant ( P<0.016 7, P<0.05). Compared to method 1, the relative uncertainties obtained by method 3 and method 4 were smaller, except for the high concentration of HbA1c level in 2020. Among the 6 pairs of comparisons (low, medium and high HbA1c in 2019 and 2020), there were 3 pairs (high HbA1c in 2019, low and medium HbA1c in 2020) and 2 pairs (low and high HbA1c in 2020) of differences with statistical significance (all P<0.016 7). Conclusion:The uncertainty evaluation of HbA1c detection in clinical laboratory should be evaluated based on IQC and trueness verification data.

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 establish the sex-, age-and season-specific (month) reference intervals (RI) for thyroid stimulating hormone (TSH) measurement by big data and indirect method in adults.Methods:TSH data of anonymous patients were collected from Beijing Chaoyang Hospital Affiliated to Capital Medical University in 2016, the data were selected and outliers were removed. Indirect methods (Hoffmann method and Bhattacharya method) were used to calculate TSH reference intervals of whole population, different genders, ages and seasons (months). TSH RI from two indirect methods of total population, selected population, physical examination population was compared with RI from reagent instruction according to reference change value ( RCV) based on biological variability. Results:A total of 61 599 records were obtained from 90 699 records including 18 776 males and 42 823 females. The TSH RI were obtained by Hoffmann method: the whole population, 0.59-5.59 μIU/ml (1 μIU/ml=1 mIU/L), male, 0.53-5.16 μIU/ml, female, 0.59-6.11 μIU/ml. The upper limits of TSH RI were higher with age and in winter (January): 18-30 years old, 0.62-5.57 μIU/ml, 71-80 years old, 0.49-6.45 μIU/ml; January, 0.59-6.40 μIU/ml, August, 0.60-5.56 μIU/ml; The RI of TSH by Bhattacharya method: the whole population, 0.58-5.80 μIU/ml, male, 0.55-5.02 μIU/ml, female, 0.62-6.21 μIU/ml. The upper limits of TSH RI were also higher with age and in winter (January): 18-30 years old, 0.65-5.67 μIU/ml, 71-80 years old, 0.46-5.99 μIU/ml, January: 0.61-6.52 μIU/ml, August: 0.61-5.69 μIU/ml. Compared to RI from reagent instruction, the differences of TSH RI from two indirect methods of total population, selected population, physical examination population were acceptable.Conclusions:TSH RI was established by indirect method. With the increase of age and winter, the upper limit of TSH reference interval tends to increase.

Objective To explore the CRP harmonization by calibration using commutable trueness verification materials. Methods High and low level of CRP concentrations trueness verification materials(H and L) were prepared by Beijing center for clinical laboratories. Thesetrueness verification materials were diluted to 5 calibration points(5L, 4L+1H, 3L+2H, 1L+4H, 5H) by weighing method, respectively. These 5 points were used to calibrate four different brands of CRP detection system (Diasys, Leadman, Siemens and Roche) instead of the original procedure. Sera from 21 patients and the international standard ERM DA-474/IFCC were used to compare harmonization and trueness after calibration. Each sample above was measured twice. Results After calibration, the median of CV was reduced from 19.33％ to 2.92％ among 21 patient samples, less than the optimal CV based on biological variability (CV=10.6％). Compared with Desai, the slopes were closer to 1 from 0.90-1.09 to 0.93-0.96 after calibration. Meanwhile, if ERM-DA474/IFCC was used as the trueness verification materials, the absolute bias wasreduced from 3.08-11.07 mg/L to 0.52-2.97 mg/L which was close to theuncertainty of itself (2.5 mg/L). Conclusions Afterthe calibration which contained five linear concentration points of CRP trueness verification materials by weighing method, both harmonization and trueness of CRP were improved.

Objective To prepare the trueness verification materials of C-reactive protein (CRP) and evaluate its homogeneity, stability and commutability. Methods The high and low CRP concentrations trueness verification materials were from patient leftover sera which were pooled, mixed thoroughly, filtered and aliquoted. The homogeneity, stability and commutability of these materials were evaluated according to CNAS(China National Accreditation Service for Conformity Assessment, CNAS)-GL29:2010 "Reference materials-General and statistical principles for certification (ISO Guide35:2006)"and the Clinical and Laboratory Standards Institute (CLSI) EP30A. The trueness verification materials were used to evaluate the commutability in 10 clinical CRP detection systems, using forty-five patients' leftover sera with different CRP concentration evaluated by Deming regression in EP30A of CLSI. Meanwhile, the commutability of dilution series of ERM DA-474/IFCC were evaluated using the same method. Results A total of two CRP concentration level trueness verification materials were prepared, with high and low concentration levels of 754 and 743 vials, 1 ml each, respectively. The preparation showed good homogeneity (F