Objective Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)and network pharmacology technology combined with pharmacodynamic experiments were used to analyze the quality markers(Q-markers)in Saorilao Qingfei Zhike Capsules.Methods Using UPLC-Q-TOF-MS technology,the chemical components in different polar extracts of Saorilao Qingfei Zhike Capsules was analyzed.Potential pharmacological components were screened by using antitussive and expectorant models.The"components-targets-diseases"network was constructed and potential Q-markers were screened by network pharmacology technology.Then we conducted pharmacodynamic validation to confirm the Q-markers,which have antitussive and expectorant effects in Saorilao Qingfei Zhike Capsules.Results A total of 120 compounds were obtained from the Saorilao Qingfei Zhike Capsules through qualitative analysis.Among the extracts of different polarity,44 compounds were derived from petroleum ether extract,85 compounds were derived from ethyl acetate extract,79 compounds were derived from n-butanol extract,and 71 compounds were derived from water extract.The results of pharmacological experiments showed that among extracts of different polarity,petroleum ether extract had the best antitussive effect,while n-butanol extract had the best expectorant effect.Three core components for eliminating phlegm and relieving cough were screened through network pharmacology techniques:farcalinol,farcalinediol,and rubimaillin.Pharmacodynamic studies verified that all core components mentioned above have certain antitussive and expectorant effects.Conclusion Based on the above research,farcalinol,farcalindiol,and rubimaillin can be used as Q-markers for the antitussive and expectorant effects of Saorilao Qingfei Zhike Capsules.This paper provides reference for the quality standard of Saorilao Qingfei Zhike Capsules.

Venous thromboembolism(VTE)includes deep venous thrombosis(DVT)and pulmonary embolism(PE).Patients in intensive care unit(ICU)are often at a high risk of VTE due to combining many risk factors.Prevention strategies of VTE in critically ill patients are crucial,including identification of risk factors,the risk as-sessment of thrombosis and bleeding,mechanical prophylaxis and drug prophylaxis,effect monitoring,and quality control.Since the risk of VTE in ICU patients is high,the risk of bleeding should not be ignored.It is a challenge for ICU physicians to comprehensively evaluate the risk of thrombosis and bleeding in critically ill patients and im-plement effective preventive and monitoring measures in time.This article reviews the relevant research progress on prevention strategies of VTE in critically ill patients in order to provide clinical evidence for the prophylaxis of VTE in critically ill patients.

Objective:To investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.

The incidence and mortality of venous thromboembolism (VTE) are high in critically ill patients, and there is still a risk of VTE and bleeding after the use of fixed-dose low molecular weight heparin (LMWH) for prophylaxis. The level of anti-factor Ⅹa is not up to standard after LMWH prophylaxis in patients with surgery or trauma. The condition of critically ill patients is complicated, and the proportion of patients with low antithrombin Ⅲ is high, which can affect the prophylactic efficacy of LMWH and contribute to VTE occurrence. There is currently no consensus on whether adjusting LMWH dose according to anti-factor Ⅹa levels can reduce VTE occurrence in critically ill patients. High-quality multicenter randomized controlled studies are needed in the future to establish new approaches for precise prevention of VTE in critically ill patients.

OBJECTIVE: To describe negative conversion and rebound of patients with severe and critical acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after treatment with Nirmatrelvir/Ritonavir, and to analyze related factors associating with failure of SARS-CoV-2 negative conversion and relapse and prognosis. METHODS: A single center retrospective cohort study was conducted. Patients aged ≥ 16 years old who were diagnosed with severe or critical SARS-CoV-2 infection and took Nirmatrelvir/Ritonavir for 5 days in Peking University First Hospital from December 7, 2022 to January 27, 2023, were included. General characteristics and clinical data were collected from electronic medical record system. The Kaplan-Meier curve of SARS-CoV-2 negative conversion was drawn. Factors with P < 0.10 were incorporated into multivariate Logistic regression model to analyze the relationship between the factors and persistent nucleic acid positive and rebound. RESULTS: A total of 31 severe and 37 critical SARS-CoV-2 infection patients were included. The median duration from initiation of Nirmatrelvir/Ritonavir to negative conversion of SARS-CoV-2 for both was 6.0 days, and the negative conversion rate on day 15 was 93.5% and 86.5%, respectively. SARS-CoV-2 rebound was observed in 7 patients (11.3%), among whom were 1 severe patient and 6 critical patients. The above 7 patients with SARS-CoV-2 rebound and 6 patients with failure of SARS-CoV-2 negative conversion were compared with 55 patients with persistent negative conversion. Factors with P < 0.10, including the lowest lymphocyte count (LYM), the highest D-dimer, the highest procalcitonin (PCT), the lowest Ct value, cardiovascular diseases other than hypertension and coronary heart disease, were incorporated into multivariate Logistic regression analysis. The decreased LYM [odds ratio (OR) = 0.146, 95% confidence interval (95%CI) was 0.031-0.689, P = 0.015] and the increased PCT (OR = 2.008, 95%CI was 1.042-3.868, P = 0.037) were revealed to be independent risk factors of the failure of SARS-CoV-2 negative conversion or rebound. The proportion of mechanical ventilation and invasive ventilation were significantly higher in patients with persistent SARS-CoV-2 infection or rebound than those in patients with SARS-CoV-2 negative conversion (84.6% vs. 38.2%, 69.2% vs. 25.5%, both P < 0.01), but no significant difference in mechanical ventilation and invasive ventilation duration was observed. Compared with the patients with SARS-CoV-2 negative conversion, more patients with persistent SARS-CoV-2 infection or rebound were admitted to intensive care unit (ICU, 76.9% vs. 50.9%), and length of ICU stay in patients with persistent SARS-CoV-2 infection or rebound tended to be longer [days: 13.0 (10.3, 24.3) vs. 11.0 (5.3, 23.0), P > 0.05]. CONCLUSIONS The decreased LYM and increased PCT are independent risk factors for the failure of SARS-CoV-2 negative conversion or rebound in patients with severe and critical SARS-CoV-2 infection. Attention should be paid to these patients for their poor prognosis.
Humans ; Adolescent ; COVID-19 ; SARS-CoV-2 ; Retrospective Studies ; Ritonavir/therapeutic use* ; Critical Illness ; COVID-19 Drug Treatment

Objective: To compare 5-year disease-free survival (DFS) and overall survival (OS) rates of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for stage IB1 and tumor size <2 cm with visible or invisible tumors. Methods: We retrospectively compared the oncological outcomes of 1,484 cervical cancer patients with IB1 and tumor size <2 cm on final pathology, who received ARH (n=899) or LRH (n=585) between January 2004 and December 2016. Patients were divided into visible tumor subgroup (ARH: n=668, LRH: n=444) and invisible tumor subgroup (ARH: n=231, LRH:n=141) according to tumor type. Results: LRH and ARH showed similar 5-year DFS and OS rates (93.3% vs. 93.1%, p=0.997;96.2% vs. 97.5%, p=0.351) in total study population. LRH was not associated with worse 5-year DFS rate (hazard ratio [HR]=0.96; 95% confidence interval [CI]=0.58–1.58; p=0.871) or OS rate (HR=1.37; 95% CI=0.65–2.89; p=0.409) by multivariable analysis. In the visible tumor subgroups, LRH and ARH showed similar 5-year DFS and OS rates (91.9% vs. 91.9%, p=0.933; 95.0% vs. 96.9%, p=0.276), and LRH was not associated with worse 5-year DFS or OS rate (p=0.804, p=0.324). In the invisible tumor subgroups, LRH and ARH also showed similar 5-year DFS and OS rates (97.3% vs. 97.1%, p=0.815; 100% vs. 99.5%, p=0.449), and LRH was not associated with worse 5-year DFS rate (p=0.723). Conclusions Among patients with stage IB1 and tumor size <2 cm, whether the tumor is visible or not, the oncological outcomes of LRH and ARH among cervical cancer patients are comparable. This suggests that LRH may be suitable for stage IB1 and tumor size <2 cm with visible or invisible tumors.

Objective:To investigate the relationship between albumin (ALB) level immediately after major abdominal surgery and postoperative acute kidney injury (AKI) in critically ill patients.Methods:A retrospective cohort study was conducted. Patients who accepted the major abdominal surgery admitted to the department of intensive care unit (ICU) of the Peking University First Hospital from June 2017 to July 2018 were enrolled. Clinical data including the postoperative ALB level and renal function were collected. Patients were divided into postoperative AKI group and postoperative non-AKI group according to the AKI diagnosis and staging criteria of Kidney Disease: Improving Global Outcomes (KIDGO). The risk factors of perioperative AKI occurrence were analyzed, and multivariate Logistic regression analysis was performed. The receiver operator characteristic curve (ROC curve) was plotted for the ALB level to predict the occurrence of AKI and to determine the ALB cut-off value. The Kaplan-Meier survival curve of postoperative survival of patients was drawn.Results:A total of 363 critically ill patients underwent major abdominal surgery, and 105 patients (28.9%) suffered from AKI. Compared with the non-AKI group, the patients in the AKI group were older ( t = -2.794, P = 0.005), preoperative proportions of diabetes and chronic kidney disease were higher ( χ21 = 4.613, χ22 = 5.427, both P < 0.05), the proportion of American Society of Anesthesiologists (ASA) grades and Ⅴ was higher ( χ2 = 19.444, P < 0.001), baseline serum creatinine (SCr) and preoperative brain natriuretic peptide (BNP) levels were higher ( U1 = 2.859, U2 = 2.283, both P < 0.05), preoperative ALB level was lower ( t = 3.226, P = 0.001), the proportion of preoperative use of contrast media was higher ( χ2 = 7.431, P = 0.006), the proportions of emergency surgery and using vasopressor during surgery were higher ( χ21 = 4.211, χ22 = 4.947, both P < 0.05), non-renal SOFA score and acute physiology and chronic health evaluation (APACHE) within 24 hours after ICU admission were higher ( U = 2.233, t = 3.130, both P < 0.05), and the proportion of postoperative immediate ALB less than 32 g/L was higher ( χ2 = 7.601, P = 0.006). ROC curve analysis showed that the cut-off value of immediate postoperative ALB for predicting postoperative AKI was 32 g/L, with the sensitivity was 86.7%, and the specificity was 28.3%. Multivariate Logistic regression analysis showed that ASA grade, use of contrast before surgery, baseline SCr and postoperative immediate serum ALB level below 32 g/L were independent risk factors for AKI [odds ratio ( OR) and 95% confidence interval (95% CI) were 2.248 (1.458-3.468), 2.544 (1.332-4.857), 1.018 (1.008-1.027) and 2.685 (1.383-5.212), respectively, all P < 0.01]. Compared with the non-AKI group, the proportion of patients with AKI undergoing mechanical ventilation in ICU was higher ( χ2 = 13.635, P < 0.001), mechanical ventilation duration, length of ICU stay, postoperative hospital stay were longer ( U1 = 2.530, U2 = 5.032, U3 = 3.200, all P < 0.05), more postoperative complications except AKI ( U = 4.799, P < 0.001), and in-hospital mortality and total hospitalization cost were higher ( χ2 = 11.681, U = 3.537, both P < 0.001). Compared with the group with postoperative immediate serum ALB ≥ 32 g/L, the proportion of mechanical ventilation in ICU of the ALB < 32 g/L group was higher ( χ2 = 33.365, P < 0.001), the length of ICU stay and postoperative hospital stay were longer ( U1 = 3.246, U2 = 4.563, both P < 0.001), more postoperative complications except AKI ( U = 3.328, P = 0.001), total hospitalization cost was higher ( U = 4.127, P < 0.001). Conclusion:For critically ill patients underwent major abdominal surgery, the postoperative immediate serum ALB level below 32 g/L significantly increased the risk of AKI, which was related to the poor prognosis of the patients.

Objective:To identify the risk factors for myocardial injury after non-cardiac surgery.Methods:The medical records of adult patients admitted to the intensive care unit of Peking University First Hospital after non-cardiac surgery from June 2017 to June 2018 were retrospectively collected.Myocardial injury was defined as serum cardiac troponin I concentration>0.06 μg/L within 3 days after operation, and the patients were divided into myocardial injury group and non-myocardial injury group.The perioperative data of patients were obtained through searching the electronic medical record system.The variables of which P values were less than 0.05 would enter the logistic regression analysis to stratify the risk factors for myocardial injury after non-cardiac surgery. Results:A total of 752 patients were included in the study, and the incidence of myocardial injury occurred after non-cardiac surgery was 15.7%.Emergency operation and highest lactic acid concentration during operation were the independent risk factors for myocardial injury after non-cardiac surgery.Conclusion:Emergency operation and highest lactic acid concentration during operation are the independent risk factors for myocardial injury after non-cardiac surgery.

The high incidence of coronavirus disease 2019 (COVID-19) and high mortality of critical patients have posed a great challenge to global public health resources. Currently there are no specific antiviral drugs and vaccines available for COVID-19, which has drawn the attention to the usefulness of convalescent plasma (CP) again, so the application of CP in the adult patients with COVID-19 is reviewed. The main contents include the possible mechanism of CP, the evidence of CP in the treatment of COVID-19 patients, the safety of clinical application of CP and the main factors affecting the clinical effect of CP, which may provide some basis for clinicians to choose CP for the treatment of adult patients with COVID-19.

Objective:To study the relationship between vitamin D level and muscle mass and grip strength in elderly patients with type 2 diabetes mellitus (T2DM).Methods:From May 2016 to January 2018, 201 patients with type 2 diabetes mellitus aged ≥ 60 who were admitted to the Department of endocrinology of Xuanwu Hospital were selected for prospective study. According to 25-hydroxyvitamin D level(25(OH)D), the patients were divided into the vitamin D deficiency group (25(OH)D<20 μg/L, 140 cases) and the non-deficiency group (20 μg/L≤25(OH)D<70 μg/L, 61 cases). The grip strength, walking speed and muscle mass of upper and lower limbs were measured.Physical examination and laboratory examination were carried out.Results:There was no significant difference between the two groups ( P>0.05). The grip strength, upper limb and lower limb muscle contents in the non deficiency group were significantly higher than those in the deficiency group ((33.49±9.43) kg vs.(29.59±10.30) kg, (4.99±1.09) kg vs.(4.57±1.11) kg, (15.69±3.10) kg vs.(14.54±3.03) kg, P=0.01, 0.015, 0.017). Multivariate logistic regression analysis showed that vitamin D deficiency was independently related to grip strength and lower limb muscle mass( OR=1.286, 95% CI: 1.197-1.346, P<0.01; OR=1.231, 95% CI: 1.102-1.283, P<0.05). Conclusion:Vitamin D deficiency is a risk factor for the decrease of grip strength and lower extremity muscle mass in elderly patients with type 2 diabetes.