Septic shock,a life-threatening subset of sepsis characterized by profound cardiovascular dysfunction,remains a leading contributor to global morbidity and mortality.Early identification and warning are critical to reducing septic shock-related mortality.This article reviewed the definition,diagnostic criteria,early clinical manifestations,and biomarkers of septic shock,providing reference for early diagnosis of septic shock and clinical basis for improving patient prognosis.

Innovative drugs are defined as new chemical entities that play a vital role in the treatment and maintenance of human health. While single-target innovative drugs have achieved notable success, they face limitations in addressing the increasingly complex and precise spectra of diseases. The advent of multi-target innovative drugs offers new opportunities, supported by a growing body of pharmacological evidence. Herbal medicines are recognized as valuable sources of multi-target therapeutics due to their proven efficacy in treating complex diseases. However, the identification and validation of such drugs from herbal sources continue to pose significant challenges. This paper presents a comprehensive review of the literature on traditional Chinese medicine, integrated medicine, chemistry, and biology from 2015 to 2025. It summarizes the strategies employed in integrating traditional Chinese and Western medicine for innovative drug development, along with successful application cases. We believe these efforts will deepen understanding of the current landscape, accelerate the discovery of multi-target innovative drugs from herbal medicine, and contribute to addressing major human health challenges.

Septic shock,a life-threatening subset of sepsis characterized by profound cardiovascular dysfunction,remains a leading contributor to global morbidity and mortality.Early identification and warning are critical to reducing septic shock-related mortality.This article reviewed the definition,diagnostic criteria,early clinical manifestations,and biomarkers of septic shock,providing reference for early diagnosis of septic shock and clinical basis for improving patient prognosis.

Non-invasive respiratory support（NIRS）is one of the important respiratory support strategies for pediatric acute respiratory distress syndrome.Early application of NIRS may reduce or avoid the use of tracheal intubation or invasive mechanical ventilation,which has been widely recognized as one of the sequential treatment methods after extubation in clinical practice.But it cannot be ignored that it may lead to adverse consequences such as delayed intubation.This review mainly discussed the benefits and risks of NIRS in pediatric acute respiratory distress.

Objective:To explore the effect of augmented renal clearance(ARC)on 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio(AUC 24/MIC)of vancomycin and prognosis in critical children, thus to provide proposal for individual dosage regimen. Methods:Sixty-five critical children treated with vancomycin, who suffered from sepsis/septic shock, were brought into this retrospective cohort study.According to estimate glomerular filtration rate, these children were divided into ARC group ( n=27) and normal group ( n=38). The influencing factor of AUC 24/MIC of vancomycin and therapy prognosis for two groups were detected and analyzed. Results:There were no significant differences between two groups in basic setting (age, sex, weight), scores of pediatric sequential organ failure assessment and pediatric risk of mortality Ⅲ, infection markers (C-reactive protein and procalcitonin), glutamic-pyruvic transaminase, hypoproteinemia, usage of diuretic and vasoactive agent( P>0.05). The patients from ARC group showed lower levels than those from normal group in AUC 24/MIC of vancomycin[375.2(300.8, 489.4) vs. 443.6(412.3, 593.2), Z=2.263, P=0.024] and it′s target achievement ratio (TAR)(40.7% vs. 76.3%, χ2=8.440, P=0.005). When usage of diuretic and vasoactive agent, the AUC 24/MIC of ARC group was lower than that of normal group( P<0.05). But there was no significant difference between ARC group and normal group regarding hypoproteinemia( P>0.05). The days of body temperature steady at least 48 hours[7.0(5.5, 9.0)d vs. 6.0(5.0, 8.0)d], the length of hospital stay[39.0(21.0, 58.0)d vs. 20.5(16.0, 28.0)d], the length of PICU stay[14.0(9.0, 31.5)d vs. 10.0(5.0, 15.0)d] were longer than those in normal group( P<0.05). There were no significant differences between ARC group and normal group regarding days of ventilation and infectious markers decreased at least 50%, as well as 28-days mortality( P>0.05). The multivariable analysis showed that the presence of ARC, hypoproteinemia, use of diuretics and vasoactive agent were significantly associated with AUC 24/MIC of vancomycin( P<0.05). Conclusion:ARC may down regulate levels of AUC 24/MIC and TAR of vancomycin.During ARC period, the usage of diuretic and vasoactive agent could affect the AUC 24/MIC of vancomycin.Individual dosage regimen should be employed for critical children suffered with ARC.

Acute respiratory distress syndrome(ARDS) is one of the challenging critical diseases in pediatric intensive care unit.Continuous renal replacement therapy(CRRT), playing important roles in the treatment of critical illness, has also become one of the hot spots in the treatment of patients with ARDS.Although CRRT technology has not been systematically recommended in the guideline of ARDS managements, numerous studies indicated that CRRT could improve survival and prognosis of ARDS, among which the impact on the clearance of inflammatory factors and fluid management of ARDS deserves attention.

Objective:To analyze the early clinical features of children with coronavirus disease 2019 (COVID-19) in order to further improve the understanding of the disease.Methods:A total of 312 children with COVID-19 under 16 years old who were first diagnosed in the children′s fever clinic at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from March to May 2022 were retrospectively analyzed.The epidemiology, early clinical features and blood routine results of children were described, and the blood routine results among different age groups were compared.Results:The median age of 312 children was 3.15(1.47, 6.51) years.The proportion of infection rate of children with different ages from high to low were 1~3 years old, > 6 years old, 3~6 years old and ≤ 1 year old.Only 17 (5.4%) cases had underlying diseases.Additionally, 70.2% patients had definite positive case reports in their residential communities, and 65.1% showed a familial cluster.Moreover, 96.2% patients had fever and 52.9% patients had respiratory symptoms.The main symptoms are fever (96.2%), cough (38.1%), runny nose (20.2%), vomiting (14.7%), sore throat (11.5%), poor appetite (6.7%), nasal congestion (4.5%), expectoration (4.5%), convulsion (4.2%), diarrhea (3.8%), etc.Among 309 children, 11.3% patients had increased white blood cell count, especially in children over 6 years old ( P=0.006); 31.7% patients had decreased lymphocyte count and 32.4% had increased C-reactive protein.The positive rate of point-of-care testing was as high as 99%. Conclusion:Children with COVID-19 in Shanghai had the characteristics of familial cluster.The main symptoms are fever and respiratory symptoms.Most of the blood routine leukocytes have no obvious changes, and a few have lymphopenia and C-reactive protein elevation.Point-of-care testing detection can help the children′s fever clinic to early screen COVID-19.

Objective:To investigate the prognostic value of proprotein convertase subtilisin/kexin type 9 (PCSK9) and blood lipid indexes in patients with sepsis.Methods:Patients with sepsis or septic shock who were ≥ 18 years old and met the Sepsis-3.0 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to October 2021 were enrolled. Healthy adults at the same period were selected as healthy control group. Baseline characteristics, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) score were recorded. Venous blood samples were collected within 24 hours after diagnosis, and serum PCSK9 was determined by enzyme-linked immunosorbent assay (ELISA) at 1, 3 days and 5 days. Meanwhile, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and lipoprotein A were detected. The differences of each index between sepsis group (28-day death group and survival group) and healthy control group were compared. Meanwhile, the indexes of patients with different severity and 28-day prognosis in sepsis group were compared. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCSK9 and blood lipid for the prognosis of sepsis. Multivariate Logistic regression was used to analyze the influencing factors for the prognosis of sepsis, and the Kaplan-Meier survival curve at 28th day was drawn.Results:There were 50 patients in sepsis group (including 19 patients with sepsis, 31 patients with septic shock) and 27 patients in healthy control group. In the sepsis group, 19 patients died and 31 patients survived within 28 days. The serum PCSK9 in the sepsis group was significantly higher than that in the healthy control group [μg/L: 223.09 (198.47, 250.82) vs. 188.00 (165.27, 214.90), P < 0.01], and HDL-C, LDL-C, TC and lipoprotein A were significantly lower than those in the healthy control group [HDL-C (mmol/L): 0.82±0.35 vs. 1.45±0.24, LDL-C (mmol/L): 1.53 (1.14, 2.47) vs. 2.89 (2.55, 3.19), TC (mmol/L): 2.03 (1.39, 2.84) vs. 4.24 (3.90, 4.71), lipoprotein A (g/L): 8.80 (5.66, 17.56) vs. 27.03 (14.79, 27.03), all P < 0.01]. PCSK9 in the sepsis death group was higher than that in the survival group [μg/L: 249.58 (214.90, 315.77) vs. 207.01 (181.50, 244.95), P < 0.01], and the HDL-C, LDL-C and TC were lower than those in the survival group [HDL-C (mmol/L): 0.64±0.35 vs. 0.93±0.30, LDL-C (mmol/L): 1.32±0.64 vs. 2.08±0.94, TC (mmol/L): 1.39 (1.01, 2.23) vs. 2.69 (1.72, 3.81), all P < 0.01]. With the progression of the disease, the PCSK9 in the sepsis death group and the survival group was significantly lower than that within 1 day of diagnosis (all P < 0.05). ROC curve analysis showed that PCSK9 had higher predictive value of 28-day death than HDL-C, LDL-C, TC [area under ROC curve (AUC) and 95% confidence interval (95% CI): 0.748 (0.611-0.885) vs. 0.710 (0.552-0.868), 0.721 (0.575-0.867), 0.702 (0.550-0.854)]. Multivariate Logistic regression analysis showed that PCSK9 was an independent risk factor affecting the 28-day prognosis of sepsis (β value was 1.014, P = 0.020). Kaplan-Meier survival curve analysis showed that when PCSK9 ≥ 208.97 μg/L, with the increase of PCSK9, the 28-day survival rate of sepsis patients decreased significantly. Conclusions:PCSK9, HDL-C, LDL-C and TC can all predict the 28-day prognosis of patients with sepsis. The prognostic value of PCSK9 is the highest. PCSK9 is an independent risk factor affecting the prognosis of sepsis. In the early stage of the disease, PCSK9 may have a good predictive value for the prognosis of sepsis. When PCSK9 ≥ 208.97 μg/L, the 28-day survival rate decreased significantly.

Recruitment maneuver(RM) refers to the process of reopening collapsed alveoli through transient lung inflations with high pressure during the mechanical ventilation in order to improve arterial oxygenation and respiratory mechanics,attenuate ventilator-induced lung injury.At present,a large number of animal experiments and clinical studies have focused on the effect of RM or factors affecting RM in acute respiratory distress syndrome.Pulmonary edema is an important pathophysiological feature of acute respiratory distress syndrome,so the effect of RM on pulmonary edema is worthy of our attention.Here is to make a review of the current progress.

Pediatric acute respiratory distress syndrome( PARDS) is one of the most challenging and severe illness in PICU. Proper liquid treatment can reduce the degree of pulmonary edema in patients,improve oxygenation,decrease duration of mechanical ventilation and so on. In this article,we reviewed recent studies on the relationship between fluid overload and clinical effect and conservative fluid therapy,to provide guid-ances for the selection of optimal treatment of restrictive fluid therapy for PARDS and the direction of the next related research.