PURPOSE: Assessing fluid responsiveness relying on central venous oxygen saturation (ScvO₂) yields varied outcomes across several studies. This study aimed to determine the ability of the change in ScvO₂ (ΔScvO₂) to detect fluid responsiveness in ventilated septic shock patients and potential influencing factors. METHODS: In this prospective, single-center study, all patients conducted from February 2023 to January 2024 received fluid challenge. Oxygen consumption was measured by indirect calorimetry, and fluid responsiveness was defined as an increase in cardiac index (CI) ≥ 10% measured by transthoracic echocardiography. Multivariate linear regression analysis was conducted to evaluate the impact of oxygen consumption, arterial oxygen saturation, CI, and hemoglobin on ScvO₂ and its change before and after fluid challenge. The Shapiro-Wilk test was used for the normality of continuous data. Data comparison between fluid responders and non-responders was conducted using a two-tailed Student t-test, Mann Whitney U test, and Chi-square test. Paired t-tests were used for normally distributed data, while the Wilcoxon signed-rank test was used for skewed data, to compare data before and after fluid challenge. RESULTS: Among 49 patients (31 men, aged (59 ± 18) years), 27 were responders. The patients had an acute physiology and chronic health evaluation II score of 24 ± 8, a sequential organ failure assessment score of 11 ± 4, and a blood lactate level of (3.2 ± 3.1) mmol/L at enrollment. After the fluid challenge, the ΔScvO₂ (mmHg) in the responders was greater than that in the non-responders (4 ± 6 vs. 1 ± 3, p = 0.019). Multivariate linear regression analysis suggested that CI was the only independent influencing factor of ScvO₂, with R² = 0.063, p = 0.008. After the fluid challenge, the change in CI became the only contributing factor to ΔScvO₂ (R² = 0.245, p < 0.001). ΔScvO₂ had a good discriminatory ability for the responders and non-responders with a threshold of 4.4% (area under the curve = 0.732, p = 0.006). CONCLUSION ΔScvO₂ served as a reliable surrogate marker for ΔCI and could be utilized to assess fluid responsiveness, given that the change in CI was the sole contributing factor to the ΔScvO₂. In stable hemoglobin conditions, the absolute value of ScvO₂ could serve as a monitoring indicator for adequate oxygen delivery independent of oxygen consumption.
Humans ; Shock, Septic/blood* ; Male ; Female ; Middle Aged ; Prospective Studies ; Oxygen Saturation ; Aged ; Fluid Therapy ; Oxygen/blood* ; Oxygen Consumption ; Adult

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes and related risk factors in children with mycoplasma pneumoniae pneumonia(MPP).Methods The clinical data of 420 children with MPP admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine were collected.The clinical data included gender,age,history of respiratory tract diseases,TCM syndromes,MPP classification,cough duration,fever duration,fever peak value,laboratory indicators of C-reactive protein(CRP),procalcitonin(PCT)and lactate dehydrogenase(LDH),and the complication of infection.SPSS 26.0 software was used for data statistics,and then the distribution of TCM syndromes in children with MPP and its correlation with various clinical data,as well as the related risk factors of MPP with different classification and various TCM syndromes were explored.Results(1)Among the 420 children with MPP,there were 283 cases(67.4％)of mild MPP,76 cases(18.1％)of refractory MPP,and 61 cases(14.5％)of severe MPP.For the distribution of TCM syndromes,there were 152 cases(36.2％)of wind-heat obstructing the lung syndrome,141 cases(33.6％)of phlegm-heat obstructing the lung syndrome,77 cases(18.3％)of damp-heat obstructing the lung syndrome,25 cases(6.0％)of toxin-heat obstructing the lung syndrome,16 cases(3.8％)of lung-spleen qi deficiency syndrome,and 9 cases(2.1％)of yin deficiency and lung heat syndrome.For the classification of infection,there were 295 cases(70.2％)of simple mycoplasma pneumoniae(MP)infection and 125 cases(29.8％)of mixed infection.(2)There were statistically significant differences in age stratification and visit season among MPP children with different TCM syndromes(P＜0.01),while no significant differences were shown in the gender,history of respiratory tract diseases,and the complication of infection(P＞0.05).(3)There were statistically significant differences in the visit season,history of respiratory tract diseases,and the complication of infection among the children with various MPP types(P＜0.05),while no significant differences were shown in the gender and age stratification(P＞0.05).(4)There were statistically significant differences in laboratory indicators of CRP and PCT and in the symptoms of cough duration,fever duration and fever peak among MPP children with different TCM syndromes(P＜0.05 or P＜0.01).(5)Significant differences were presented in laboratory indicators of PCT and LDH and in the symptoms of cough duration,fever duration and fever peak value among the children with different MPP types(P＜0.05 or P＜0.01).(6)Multivariate logistic regression analysis showed that CRP level ≥10.5 mg/L and wind-heat obstructing the lung syndrome were the independent risk factors for mild MPP(P＜0.05 or P＜0.01);fever duration≥7 days,cough duration ≥ 12 days and phlegm-heat obstructing the lung syndrome were the independent risk factors for refractory MPP(P＜0.05 or P＜0.01);cough duration ≥ 12 days,mixed infection and toxin-heat obstructing the lung syndrome were the independent risk factors for severe MPP(P＜0.01).Conclusion The results indicated that the classification MPP in children is predominated by mild MPP,and their TCM syndrome types is predominated by wind-heat obstructing the lung syndrome.The proportions of refractory MPP and damp-heat obstructing the lung syndrome increase significantly in autumn,which may be related to the characteristics of regional environment and circuit qi.The increase of CRP level and fever peak may be related to phlegm-heat obstructing the lung syndrome and toxin-heat obstructing the lung syndrome.In clinic,attention should be paid to the early use of heat-clearing and phlegm-resolving drugs or heat-clearing and toxin-removing drugs;children with the history of respiratory tract diseases and mixed infections are more likely to develop into severe MPP,and the physicians should be alert clinically.Wind-heat obstructing the lung syndrome,phlegm-heat obstructing the lung syndrome and toxin-heat obstructing the lung syndrome are the independent risk factor separately for mild MPP,refractory MPP and severe MPP,which requires timely intervention to prevent mild MPP from developing into refractory MPP or severe MPP in clinic.

Pharmaceutical cocrystals is an advanced technology to improve the physicochemical and biological properties of drugs. However, there are few studies on the in vivo metabolism of pharmaceutical cocrystals. In this study, the pharmacokinetics of wogonin cocrystal in normal rats was further studied on the basis of the previous preparation of wogonin-aloperine cocrystal. Firstly, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for simultaneous determination of wogonin and its metabolite wogonoside in rat plasma, and to investigate the methodology. The method was applied to the pharmacokinetic study of wogonin-aloperine cocrystal (Wog-Alop) in rats. The results showed that wogonin and its metabolite wogonoside had a good linear relationship in the range of 1-800 ng·mL^-1, and the precision, accuracy, matrix effect and stability in this range met the requirements of biological analysis. Compared with direct administration of wogonin, the C_max of wogonin and its metabolite in rats increased to 7.44-fold and 9.15-fold, AUC_0-t increased to 1.67-fold and 3.72-fold, and oral bioavailability of wogonin increased to 187.66% after cocrystal administration. Wog-Alop cocrystal can significantly improve the C_max, AUC, and oral bioavailability of wogonin and its metabolite, which provides a new perspective for the clinical application of wogonin. This study was approved by the Experimental Animal Ethics Review Committee of Beijing University of Chinese Medicine (approval number: BUCM-2023032307-1148).

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.

The end of the COVID-19 infection peak in 2022 prompts a backlog of cardiovascular surgical patients to gradually return to the hospital, resulting in a surge in cardiovascular surgeries. However, against the backdrop of the COVID-19 pandemic, the clinical practice of cardiovascular surgery faces many problems. Therefore, organized by Beijing Anzhen Hospital, experts in cardiovascular surgery and related fields have formulated hospital expert experience on perioperative treatment principles of cardiovascular surgery for patients infected with COVID-19. This article summarizes the clinical decision-making of patients requiring cardiovascular surgery after COVID-19 infection, and advises on the corresponding recommendations according to the existing evidence-based medical evidence as well as the actual clinical practice experience of relevant experts. The main content of the article includes special requirements for cardiovascular surgical treatment indications in patients with COVID-19 infection, selection of surgical timing, special requirements of preoperative, intraoperative and postoperative management, etc., which aims to provide COVID-19-infected patients with guidance on rational decision-making when receiving cardiovascular surgery.

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Objective To evaluate the bioequivalence of lamivudine tenofovir tablets in Chinese healthy volunteers.Methods A randomized,open,single-dose,two-period,double-crossover drug trial design was conducted.24 subjects were randomly divided into two groups,and administered orally one tablet of test preparation or one tablet of each reference preparation per period under fasting and fed condition respectively.The concentrations of lamivudine and tenofovir in plasma were determined by HPLC-MS/MS.The pharmacokinetic parameters were calculated and the bioequivalence was compared by non-compartment model of WinNonlin 7.0 program.Results The pharmacokinetic parameters of test and reference preparations after fasting oral administration:lamivudine Cmax were(2 777.74±702.55)and(2 985.00±979.23)ng·mL-1,AUC0-t were(11 977.14±2 550.67)and(12 450.22±2 336.41)ng·h·mL-1,AUC0-∞ were(12 177.69±2 526.02)and(12 660.98±2 333.30)ng·h·mL-1,respectively;tenofovir Cmax were(316.72±63.79)and(301.46±79.82)ng·mL-1,AUC0-t were(2 584.72±619.04)and(2 474.94±636.05)ng·h·mL-1,AUC0-∞ were(2 789.87±701.97)and(2 666.35±676.21)ng·h·mL-1,respectively.The pharmacokinetic parameters of test and reference preparations after fed oral administration:lamivudine Cmax were(2 079.46±583.92)and(2 084.28±517.59)ng·mL-1,AUC0-t were(10 628.86±1 751.63)and(10 573.70±2 059.54)ng·h·mL-1,AUC0-∞ were(10 827.86±1 734.39)and(10 791.93±2 098.91)ng·h·mL-1,respectively;tenofovir Cmax were(286.97±85.91)and(271.79±63.64)ng·mL-1,AUC0-t were(3 087.01±707.76)and(3 023.48±612.46)ng·h·mL-1,AUC0-∞ were(3 307.08±746.76)and(3 221.56±672.44)ng·h·mL-1,respectively.The statistical results of the 90％confidence intervals of the geometric mean ratios of Cmax,AUC0-t and AUC0-∞(test preparation/reference preparation)were all within the equivalent range of 80.00％-125.00％.Conclusion The test and reference preparations of lamivudine tenofovir tablets were bioequivalent in healthy Chinese subjects under fasting and fed conditions.

Objective To develop an ultra performance liquid chromatography/tandem mass spectrometry(UPLC-MS/MS)method for the determination of benidipine in human plasma and apply it to the pharmacokinetics study of healthy volunteers.Methods Human plasma samples were pretreated with ethyl acetate extraction.The chromatographic column was Shim-pack XR-ODS Ⅲ(1.6 μm,2.0 mm × 50.0 mm),The mobile phase consisted of water(5 mmol·L-1 ammonium acetate)-acetonitrile with a isocratic elution at a flow rate of 0.3 mL·min-1.Detection was performed using an electrospray ionization source operating in positive ion multiple reaction monitoring mode,and d5 isotope of benidipine hydrochloride was used as the internal standard.To validate the method,specificity,linearity,quantification limit,precision,recovery,stability and matrix effect were determined.Results Benedipine had a good linear relationship(r＞0.999)in the concentration range of 0.01-15.00 ng·mL-1,the extraction recovery was 78.21％-83.14％,the precision relative standard deviation was less than 6.42％,and the stability was good.No significant matrix effects were found during the determination.Six healthy volunteers took one tablet of benidipine hydrochloride(8 mg)orally for two times,the mean T1/2,Tmax and Cmax of benidipine hydrochloride orally administered to subjects were(4.57±2.92)h,(1.08±0.52)h and(7.28±1.87)ng·mL-1,respectively.Conclusion The method has high sensitivity,high efficiency,good accuracy and simple operation,which can be used for the pharmacokinetics and bioequivalence study of benidipine.

Accumulating studies have demonstrated that non-coding RNAs (ncRNAs), functioning as important regulators of transcription and translation, are involved in the establishment and maintenance of pregnancy, especially the maternal immune adaptation process. The endometrial stromal cells (ESCs), trophoblast cells, and decidua immune cells that reside at the maternal-fetal interface are thought to play significant roles in normal pregnancy and pregnancy-associated diseases. Here, we reviewed the up-to-date evidence on how microRNA, long non-coding RNA, and circular RNA regulate ESCs, trophoblast cells, and immune cells and discussed the potential applications of these ncRNAs as diagnostic and therapeutic markers in pregnancy complications.
Pregnancy ; Female ; Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; RNA, Circular/genetics* ; Trophoblasts ; Pregnancy Complications/genetics*