Plant-derived flavonoids are a potential source of drugs for the treatment of liver fibrosis.

Liver fibrosis is a dynamic pathological process that can be triggered by any chronic liver injury. If left unaddressed, it will inevitably progress to the severe outcomes of liver cirrhosis or even hepatocellular carcinoma. In the past few years, the prevalence and fatality of hepatic fibrosis have been steadily rising on a global scale. As a result of its intricate pathogenesis, the quest for pharmacological interventions targeting liver fibrosis has remained a formidable challenge. Currently, no pharmaceuticals are exhibiting substantial clinical efficacy in the management of hepatic fibrosis. Hence, it is of utmost importance to expedite the development of novel therapeutics for the treatment of this condition. Various research studies have revealed the ability of different natural flavonoid compounds to alleviate or reverse hepatic fibrosis through a range of mechanisms, which are related to the regulation of liver inflammation, oxidative stress, synthesis and secretion of fibrosis-related factors, hepatic stellate cells activation, and proliferation, and extracellular matrix synthesis and degradation by these compounds. This review summarizes the progress of research on different sources of natural flavonoids with inhibitory effects on liver fibrosis over the last decades. The anti-fibrotic effects of natural flavonoids have been increasingly studied, making them a potential source of drugs for the treatment of liver fibrosis due to their good efficacy and biosafety.

Hypericin as a promising natural bioactive naphthodianthrone: A review of its pharmacology, pharmacokinetics, toxicity, and safety.

Hypericin can be derived from St. John's wort, which is widely spread around the world. As a natural product, it has been put into clinical practice such as wound healing and depression for a long time. In this article, we review the pharmacology, pharmacokinetics, and safety of hypericin, aiming to introduce the research advances and provide a full evaluation of it. Turns out hypericin, as a natural photosensitizer, exhibits an excellent capacity for anticancer, neuroprotection, and elimination of microorganisms, especially when activated by light, potent anticancer and antimicrobial effects are obtained after photodynamic therapy. The mechanisms of its therapeutic effects involve the induction of cell death, inhibition of cell cycle progression, inhibition of the reuptake of amines, and inhibition of virus replication. The pharmacokinetics properties indicate that hypericin has poor water solubility and bioavailability. The distribution and excretion are fast, and it is metabolized in bile. The toxicity of hypericin is rarely reported and the conventional use of it rarely causes adverse effects except for photosensitization. Therefore, we may conclude that hypericin can be used safely and effectively against a variety of diseases. We hope to provide researchers with detailed guidance and enlighten the development of it.

Soil fungal communities show more specificity than bacteria for plant species composition in a temperate forest in China.

BACKGROUND: Soil microbiome is an important part of the forest ecosystem and participates in forest ecological restoration and reconstruction. Niche differentiation with respect to resources is a prominent hypothesis to account for the maintenance of species diversity in forest ecosystems. Resource-based niche differentiation has driven ecological specialization. Plants influence soil microbial diversity and distribution by affecting the soil environment. However, with the change in plant population type, whether the distribution of soil microbes is random or follows an ecologically specialized manner remains to be further studied. We characterized the soil microbiome (bacteria and fungi) in different plant populations to assess the effects of phytophysiognomy on the distribution patterns of soil microbial communities in a temperate forest in China. RESULTS: Our results showed that the distribution of most soil microbes in different types of plant populations is not random but specialized in these temperate forests. The distribution patterns of bacteria and fungi were related to the composition of plant communities. Fungal species (32%) showed higher specialization than bacterial species (15%) for different types of plant populations. Light was the main driving factor of the fungal community, and soil physicochemical factors were the main driving factor of the bacterial community. CONCLUSION: These findings suggest that ecological specialization is important in maintaining local diversity in soil microbial communities in this forest. Fungi are more specialized than bacteria in the face of changes in plant population types. Changes in plant community composition could have important effects on soil microbial communities by potentially influencing the stability and stress resistance of forest ecosystems.

One Hundred Days of Coronavirus Disease 2019 Prevention and Control in China.

The epidemic of novel coronavirus disease was first reported in China in late December 2019 and was brought under control after some 2 months in China. However, it has become a global pandemic, and the number of cases and deaths continues to increase outside of China. We describe the emergence of the pandemic, detail the first 100 days of China's response as a phase 1 containment strategy followed by phase 2 containment, and briefly highlight areas of focus for the future. Specific, simple, and pragmatic strategies used in China for risk assessment, prioritization, and deployment of resources are described. Details of implementation, at different risk levels, of the traditional public health interventions are shared. Involvement of society in mounting a whole country response and challenges experienced with logistics and supply chains are described. Finally, the methods China is employing to cautiously restart social life and economic activity are outlined.

Derivation and Validation of an Ensemble Model for the Prediction of Agitation in Mechanically Ventilated Patients Maintained Under Light Sedation.

OBJECTIVES: Light sedation is recommended over deep sedation for invasive mechanical ventilation to improve clinical outcome but may increase the risk of agitation. This study aimed to develop and prospectively validate an ensemble machine learning model for the prediction of agitation on a daily basis. DESIGN: Variables collected in the early morning were used to develop an ensemble model by aggregating four machine learning algorithms including support vector machines, C5.0, adaptive boosting with classification trees, and extreme gradient boosting with classification trees, to predict the occurrence of agitation in the subsequent 24 hours. SETTING: The training dataset was prospectively collected in 95 ICUs from 80 Chinese hospitals on May 11, 2016, and the validation dataset was collected in 20 out of these 95 ICUs on December 16, 2019. PATIENTS: Invasive mechanical ventilation patients who were maintained under light sedation for 24 hours prior to the study day and who were to be maintained at the same sedation level for the next 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 578 invasive mechanical ventilation patients from 95 ICUs in 80 Chinese hospitals, including 459 in the training dataset and 119 in the validation dataset, were enrolled. Agitation was observed in 36% (270/578) of the invasive mechanical ventilation patients. The stepwise regression model showed that higher body temperature (odds ratio for 1°C increase: 5.29; 95% CI, 3.70-7.84; p < 0.001), greater minute ventilation (odds ratio for 1 L/min increase: 1.15; 95% CI, 1.02-1.30; p = 0.019), higher Richmond Agitation-Sedation Scale (odds ratio for 1-point increase: 2.43; 95% CI, 1.92-3.16; p < 0.001), and days on invasive mechanical ventilation (odds ratio for 1-d increase: 0.95; 95% CI, 0.93-0.98; p = 0.001) were independently associated with agitation in the subsequent 24 hours. In the validation dataset, the ensemble model showed good discrimination (area under the receiver operating characteristic curve, 0.918; 95% CI, 0.866-0.969) and calibration (Hosmer-Lemeshow test p = 0.459) in predicting the occurrence of agitation within 24 hours. CONCLUSIONS: This study developed an ensemble model for the prediction of agitation in invasive mechanical ventilation patients under light sedation. The model showed good calibration and discrimination in an independent dataset.

Toxic warhead-armed antibody for targeted treatment of glioblastoma.

Glioblastoma is a fatal intracranial tumor with a poor prognosis, exhibiting uninterrupted malignant progression, widespread invasion throughout the brain leading to the destruction of normal brain tissue and inevitable death. Monoclonal antibodies alone or conjugated with cytotoxic payloads to treat patients with different solid tumors showed effective. This treatment strategy is being explored for patients with glioblastoma (GBM) to obtain meaningful clinical responses and offer new drug options for the treatment of this devastating disease. In this review, we summarize clinical data (from pubmed.gov database and clinicaltrial.gov database) on the efficacy and toxicity of naked antibodies and antibody-drug conjugates (ADCs) against multiple targets on GBM, elucidate the mechanisms that ADCs act at the site of GBM lesions. Finally, we discuss the potential strategies for ADC therapies currently used to treat GBM patients.

Gastrodin: a comprehensive pharmacological review.

Tianma is the dried tuber of Gastrodia elata Blume (G. elata), which is frequently utilized in clinical practice as a traditional Chinese medicine. Gastrodin (GAS) is the main active ingredient of Tianma, which has good pharmacological activity. Therefore, for the first time, this review focused on the extraction, synthesis, pharmacological effects, and derivatives of GAS and to investigate additional development options for GAS. The use of microorganisms to create GAS is a promising method. GAS has good efficacy in the treatment of neurological diseases, cardiovascular diseases, endocrine diseases, and liver diseases. GAS has significant anti-inflammatory, antioxidant, neuroprotective, vascular protective, blood sugar lowering, lipid-regulating, analgesic, anticancer, and antiviral effects. The mechanism involves various signaling pathways such as Nrf2, NF-κB, PI3K/AKT, and AMPK. In addition, the derivatives of GAS and biomaterials synthesized by GAS and PU suggested a broader application of GAS. The research on GAS is thoroughly summarized in this paper, which has useful applications for tackling a variety of disorders and exhibits good development value.

Lipidome is a valuable tool for the severity prediction of coronavirus disease 2019.

Objective: To describe the lipid metabolic profile of different patients with coronavirus disease 2019 (COVID-19) and contribute new evidence on the progression and severity prediction of COVID-19. Methods: This case-control study was conducted in Peking University Third Hospital, China. The laboratory-confirmed COVID-19 patients aged ≥18 years old and diagnosed as pneumonia from December 2022 to January 2023 were included. Serum lipids were detected. The discrimination ability was calculated with the area under the curve (AUC). A random forest (RF) model was conducted to determine the significance of different lipids. Results: Totally, 44 COVID-19 patients were enrolled with 16 mild and 28 severe patients. The top 5 super classes were triacylglycerols (TAG, 55.9%), phosphatidylethanolamines (PE, 10.9%), phosphatidylcholines (PC, 6.8%), diacylglycerols (DAG, 5.9%) and free fatty acids (FFA, 3.6%) among the 778 detected lipids from the serum of COVID-19 patients. Certain lipids, especially lysophosphatidylcholines (LPCs), turned to have significant correlations with certain immune/cytokine indexes. Reduced level of LPC 20:0 was observed in severe patients particularly in acute stage. The AUC of LPC 20:0 reached 0.940 in discriminating mild and severe patients and 0.807 in discriminating acute and recovery stages in the severe patients. The results of RF models also suggested the significance of LPCs in predicting the severity and progression of COVID-19. Conclusion: Lipids probably have the potential to differentiate and forecast the severity, progression, and clinical outcomes of COVID-19 patients, with implications for immune/inflammatory responses. LPC 20:0 might be a potential target in predicting the progression and outcome and the treatment of COVID-19.

[Effect of enteral nutritional support on clinical outcomes of patients with sepsis].

OBJECTIVE: To research whether clinical outcomes of patients with sepsis can be improved by higher enteral nutritional support. METHODS: A retrospective cohort method was applied. 145 patients with sepsis who were hospitalized in intensive care unit (ICU) of Peking University Third Hospital from September, 2015 to August, 2021 and met inclusion criteria as well as exclusion criteria were selected, including 79 males and 66 females, the median age was 68 (61, 73). Researchers evaluated whether there was correlation between improved modified nutrition risk in critically ill score (mNUTRIC), daily energy intake and protein supplement of patients and their clinical outcomes through Poisson log-linear regression analysis and Cox regression analysis. RESULTS: The median of mNUTRIC score of 145 hospitalized patients was 6 (3, 10), wherein 70.3% of patients (102 cases) were in high-score group (≥ 5 scores) and 29.7% of patients (43 cases) were in low-score group (< 5 scores); the average of daily protein intake in ICU was about 0.62 (0.43, 0.79) g×kg-1×d-1, and the average of daily energy intake was about 64.4 (48.1, 86.2) kJ×kg-1×d-1. As shown by Cox regression analysis, increase of mNUTRIC score, sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation II (APACHE II) were correlated to growth of in-hospital mortality [hazard ratio (HR) = 1.12, 95% confidence interval (95%CI) was 1.08-1.16, P = 0.006; HR = 1.04, 95%CI was 1.01-1.08, P = 0.030; HR = 1.08, 95%CI was 1.03-1.13, P = 0.023]. Higher average daily intake of protein and energy as well as lower mNUTRIC, SOFA, and APACHE II scores were also significantly correlated to lower 30-day mortality (HR = 0.45, 95%CI was 0.25-0.65, P < 0.001; HR = 0.77, 95%CI was 0.61-0.93, P < 0.001; HR = 1.10, 95%CI was 1.07-1.13, P < 0.001; HR = 1.07, 95%CI was 1.02-1.13, P = 0.041; HR = 1.15, 95%CI was 1.05-1.23, P = 0.014); however, there was no significant correlation between gender as well as number of complications and in-hospital mortality. Within 30 days of attack of sepsis, the average daily intake of protein and energy were not correlated to days of non-ventilator (HR = 0.66, 95%CI was 0.59-0.74, P = 0.066; HR = 0.78, 95%CI was 0.63-0.93, P = 0.073). Increase of patients' average daily intake of protein and energy were significantly correlated to a lower in-hospital mortality (HR = 0.41, 95%CI was 0.32-0.50, P < 0.001; HR = 0.87, 95%CI was 0.84-0.92, P < 0.001), shorter ICU stay (HR = 0.46, 95%CI was 0.39-0.53, P < 0.001; HR = 0.82, 95%CI was 0.78-0.86, P < 0.001), and hospital stay (HR = 0.51, 95%CI was 0.44-0.58, P < 0.001; HR = 0.77, 95%CI was 0.68-0.88, P < 0.001). According to correlation analysis, among patients with mNUTRIC score ≥ 5, increasing daily intake of protein and energy can reduce in-hospital mortality (HR = 0.44, 95%CI was 0.32-0.58, P < 0.001; HR = 0.73, 95%CI was 0.69-0.77, P < 0.001), and 30-day mortality (HR = 0.51, 95%CI was 0.37-0.65, P < 0.001; HR = 0.90, 95%CI was 0.85-0.96, P < 0.001); the receiver operator characteristic curve (ROC curve) further confirmed that higher protein intake had good predictive value for inpatient mortality area under the curve (AUC) = 0.96 and 30-day mortality (AUC = 0.94); higher emergy intake had good predictive value for inpatient mortality (AUC = 0.87) and 30-day mortality (AUC = 0.83). By contrast, among patients with mNUTRIC score < 5, it is only discovered that increasing daily intake of protein and energy can reduce 30-day mortality of patients (HR = 0.76, 95%CI was 0.69-0.83, P < 0.001). CONCLUSIONS: The increase of average daily intake of protein and energy for patients with sepsis is significantly correlated to reduction of in-hospital mortality and 30-day mortality, shorter ICU stay, and hospital stay. The correlation is more significant in patients with high mNUTRIC score, and higher intake of protein and energy can bring down in-hospital mortality and 30-day mortality. As for patients with low mNUTRIC score, nutritional support cannot improve prognosis of the patients significantly.

Recent advances in glucose-oxidase-based nanocomposites for diabetes diagnosis and treatment.

Glucose oxidase (GOx) has attracted a lot of attention in the field of diabetes diagnosis and treatment in recent years owing to its inherent biocompatibility and glucose-specific catalysis. GOx can effectively catalyze the oxidation of glucose in the blood to hydrogen peroxide (H2O2) and glucuronic acid and can be used as a sensitive element in biosensors to detect blood glucose concentrations. Nanomaterials based on the immobilization of GOx can significantly improve the performance of glucose sensors through, for example, reduced electron tunneling distance. Moreover, various insulin-loaded nanomaterials (e.g., metal-organic backbones, and mesoporous silica nanoparticles) have been developed for the control of blood glucose concentrations based on GOx catalytic chemistry. These nano-delivery carriers are capable of releasing insulin in response to GOx-mediated changes in the microenvironment, allowing for a rapid return of the blood microenvironment to a normal state. Therefore, glucose biosensors and insulin delivery vehicles immobilized with GOx are important tools for the diagnosis and treatment of diabetes. This paper reviews the characteristics of various GOx-based nanomaterials developed for glucose biosensing and insulin-responsive release as well as research progress, and also highlights the current challenges and opportunities facing this field.

Trimethylated chitosan-coated flexible liposomes with resveratrol for topical drug delivery to reduce blue-light-induced retinal damage.

LED-related blue-light-induced damage can cause eye diseases. However, drug delivery in patients with ocular diseases is faced with various challenges. In this study, we developed flexible liposomes based on trimethylated chitosan (TMC-Lipo) to deliver resveratrol for the treatment of retinal diseases. Flexible liposomes can easily cross various biological barriers. Chitosan and its derivatives have adhesive properties and are widely used in mucoadhesive drug delivery systems. Therefore, we wrapped flexible liposomes with trimethylated chitosan via electrostatic adsorption. The charge of the flexible liposomes became positive after encapsulation in TMC, and they remained stable in artificial tears. We assessed the safety of TMC-Lipo in cellular and zebrafish experiments and found that it can be safely used. In addition, treatment with TMC-Lipo significantly reduced H2O2-induced damage to ARPE-19 cells, restored mitochondrial membrane potential, and protected the cells. TMC-Lipo more easily reached the posterior ocular segment of the mice than liposome nanoparticles and attenuated blue-light-induced retinal cytopathy. Our study demonstrates that effective eye drop formulations can be developed based on trimethylated chitosan, which provides a promising approach for the treatment of ocular diseases.

Proteomic analysis reveals mechanisms of mixed wastewater with different N/P ratios affecting the growth and biochemical characteristics of Chlorella pyrenoidosa.

Effects of different nutrient ratios on the biochemical compositions of microalgae and the changes were rarely studied at the molecular level. In this study, the impacts of various nitrogen to phosphorus (N/P) ratios on growing of C. pyrenoidosa, as well as biochemical compositions and the metabolic regulation mechanism in mixed sewage, were investigated. The results suggested that 18 was optimal N/P ratio, while the dry weight (1.0 g/L), chlorophyll-a (Chla) (3.63 mg/L), and lipid production (0.28 g/L) were all the highest comparing with other groups. In contrast, the protein production (0.37 g/L) was the least. The nature of the regulatory mechanisms inthe metabolic pathways of these biochemical compositions was revealed by proteomic results, and there were 62 different expression proteins (DEPs) taken part in fatty acid and lipid biosynthesis metabolism (FA), amino acid biosynthesis metabolism (AA), photosynthesis (PHO), carbon fixation in photosynthetic organisms (CFP), and central carbon metabolism (CCM).

[Incidence of maternal sepsis in ICUs of hospitals in Beijing: a multicenter cohort study].

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) centigrade, and the median white blood cell count (WBC) was 17.2 (13.2, 21.3)×109/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.

Effects of tillage and biochar on soil physiochemical and microbial properties and its linkage with crop yield.

Vertisols are clayey soils with a high potential for improving production. Therefore, understanding the impact of tillage and fertilization on soil physicochemical properties and microbial community is essential for improving the vertisols with a high montmorillonite and smectite clay content. A 3-year field experiment was conducted to compare the effects of different tillage and fertilization practices at three depths of the vertisol under the wheat-maize cropping system in the North China Plain. The experimental treatments included rotary tillage without fertilization (R-CK), rotary tillage with chemical nitrogen (N), phosphorus (P), and potassium (K) fertilization (R-NPK), R-NPK plus biochar (R-NPKB), deep tillage without fertilization (D-CK), deep tillage with chemical N, P, and K fertilization (D-NPK), and D-NPK plus biochar (D-NPKB). The results showed that D-NPKB significantly improved winter wheat and summer maize yields by 14.4 and 3.8%, respectively, compared with R-NPK. The nitrate (NO3 --N) content of the deeper soil layer in D-NPKB was significantly higher than that in D-NPK. Meanwhile, biochar application increased the pH in the three layers. Compared with R-NPK, D-NPKB significantly increased the average content of available phosphorus (AP), soil organic carbon (SOC), and total nitrogen (TN) by 73.7, 18.5, and 19.0%, respectively. Meanwhile, Gaiellale, Sphingomonadaceae, and Nocardioidaceae were the predominant bacteria at the family level across all treatments, with a total relative proportion ranging from 14.1 to 23.6%. In addition, the abundance of Bacillaceae in deep tillage was 9.4% higher in the 20-30-cm soil layer than that in rotary tillage. Furthermore, the correlation analysis revealed a significant positive correlation between crop yield and chemical factors such as NO3 --N and the abundances of Gaiellalea, Sphingomonadaceae, and Nocardioidaceae. The findings collectively indicated that deep tillage combined with biochar application could increase the soil nutrients and modify the bacterial structure in the deeper soil layer and therefore will be beneficial for improving the productivity of the vertisols.

Changes in the Distribution Preference of Soil Microbial Communities During Secondary Succession in a Temperate Mountain Forest.

Soil microbes play a crucial role in a forest ecosystem. However, whether the distribution of bacteria and fungi in different forest succession stages is random or following ecological specialization remains to be further studied. In the present study, we characterized soil bacterial and fungal communities to determine their distribution preference, with different succession communities in a temperate mountain forest. The Kruskal-Wallis method was used to analyze structural differences between bacterial and fungal communities in different succession processes. The specificity of soil microbial distribution in a secondary forest was studied by network analysis. The torus-translation test was used to analyze the species distribution preference of soil microbes in different succession stages. Results showed that the species composition of soil bacteria and fungi differed significantly in different succession processes. The modularity index of fungi (0.227) was higher than that of bacteria (0.080). Fungi (54.47%) had specific preferences than bacteria (49.95%) with regard to forests in different succession stages. Our work suggests that the distribution pattern of most soil microbes in a temperate mountain forest was not random but specialized in temperate mountain forests. Different microbes showed different distribution preferences. Fungi were more sensitive than bacteria during secondary succession in a temperate mountain forest. In addition, microbe-environment relations varied during secondary succession. Our results provided new insight into the mechanism through which complex soil microbial communities responded to changes in forest community succession.

[Analysis of risk factors of hyperpyrexia suffered by post neurosurgical patients after removal of drainage tube].

OBJECTIVE: To analyze the risk factors of hyperthermia after removal of drainage tubes in patients after neurosurgery. METHODS: The clinical data of 146 patients after neurosurgery with indwelling drainage tubes admitted to the department of critical care medicine of Pecking University Third Hospital from January 2019 to July 2021 were analyzed retrospectively. The patients were divided into hyperthermia group (body temperature ≥ 39 centigrade) and non-hyperthermia group (body temperature < 39 centigrade) according to whether their body temperatures within 24 hours after removal of drainage tubes. General clinical data and outcomes of the two groups were collected, and different tendentious scores were matched with the hyperthermia group and non-hyperthermia group based on Glasgow coma score (GCS), respectively. After such matching, the clinical baseline characteristics [age, gender, admission diagnosis, major complications, acute physiology and chronic health evaluation II (APACHE II) at admission, GCS], number of days of drainage tubes retention, location of drainage tubes, microbial culture results before removal of drainage tubes, white blood cell (WBC) and neutrophil ratio (NEU%) before and after removal of drainage tubes as well as clinical outcomes of the cohort patients were analyzed. The primarily outcome was in-hospital mortality, and then the length of intensive care unit (ICU) stay. RESULTS: A total of 146 patients after neurosurgery were included, 28 of which developed hyperthermia after removal of drainage tubes. The GCS scores at admission in the hyperthermia group were significantly lower than that in the non-hyperthermia group, while the proportion of hypertension and diabetes in the hyperthermia group was significantly higher than that in the non-hyperthermia group. Based on GCS scores, the two groups, each of which included 28 patients, were matched with tendentious scores, and there was no significant difference in gender, age, GCS scores and the proportion of hypertension and diabetes between the two groups. The main disease for patients upon admission was cerebral hemorrhage (53.6%, 30/56). The proportion of indwelling ventricular drainage tube retention in the hyperthermia group was significantly higher than that in the non-hyperthermia group [32.1% (9/28) vs. 7.1% (2/28), P < 0.05], but there was no significant difference in the location of other drainage tubes between the two groups. The proportion of lumbar puncture in the hyperthermia group was also significantly higher than that in the non-hyperthermia group [25.0% (7/28) vs. 0 (0/28), P < 0.05]. Compared with the non-hyperthermia group, WBC [×109/L: 13.0 (9.5, 15.2) vs. 11.5 (8.8, 13.3)] of 1 day before removal of drainage tubes, NEU% [0.892 (0.826, 0.922) vs. 0.843 (0.809, 0.909)] after removal of drainage tubes and positive rate of drainage-fluid culture or drainage-tube-tip culture [7.1% (2/28) vs. 0% (0/28)] in the hyperthermia group increased, but there were not significant differences. There was no significant difference in the proportion of pulmonary, urinary system and blood flow infection before removal of drainage tubes in the two groups. In terms of primary outcomes, compared with the non-hyperthermia group, the length of ICU stay [days: 17.0 (8.0, 32.3) vs. 8.5 (1.0, 16.8), P < 0.05] in the hyperthermia group was significantly prolonged, and the in-hospital mortality [35.7% (10/28) vs. 10.7% (3/28), P < 0.05] in the hyperthermia group was obviously increased. The positive rate of carbapenem-resistant bacteria culture [32.1% (9/28) vs. 3.6% (1/28), P < 0.05] in the hyperthermia group during hospitalization was significantly higher than that in the non-hyperthermia group. CONCLUSIONS: Hyperthermia after removal of drainage tubes for patients after neurosurgery can significantly prolong the length of ICU stay and increase the in-hospital mortality, which may be related to the secondary infection caused by indwelling intracranial drainage tubes and the intracranial spread of bacteria caused by removal of drainage tubes, as well as the intracranial multidrug-resistant bacterial infection caused by the drainage tubes.

Therapeutic Efficacy of Human Mesenchymal Stem Cells With Different Delivery Route and Dosages in Rat Models of Spinal Cord Injury.

Recent studies have shown that the use of mesenchymal stem/stromal cells (MSCs) may be a promising strategy for treating spinal cord injury (SCI). This study aimed to explore the effectiveness of human umbilical cord-derived MSCs (hUC-MSCs) with different administration routes and dosages on SCI rats. Following T10-spinal cord contusion in Sprague-Dawley rats (N = 60), three different dosages of hUC-MSCs were intrathecally injected into rats (SCI-ITH) after 24 h. Intravenous injection of hUC-MSCs (SCI-i.v.) and methylprednisolone reagent (SCI-PC) were used as positive controls (N = 10/group). A SCI control group without treatment and a sham operation group were injected with Multiple Electrolyte Injection solution. The locomotor function was assessed by Basso Beattie Bresnahan (BBB) rating score, magnetic resonance imaging (MRI), histopathology, and immunofluorescence. ELISA was conducted to further analyze the nerve injury and inflammation in the rat SCI model. Following SCI, BBB scores were significantly lower in the SCI groups compared with the sham operation group, but all the treated groups showed the recovery of hind-limb motor function, and rats receiving the high-dose intrathecal injection of hUC-MSCs (SCI-ITH-H) showed improved outcomes compared with rats in hUC-MSCs i.v. and positive control groups. Magnetic resonance imaging revealed significant edema and spinal cord lesion in the SCI groups, and significant recovery was observed in the medium and high-dose hUC-MSCs ITH groups. Histopathological staining showed that the necrotic area in spinal cord tissue was significantly reduced in the hUC-MSCs ITH-H group, and the immunofluorescence staining confirmed the neuroprotection effect of hUC-MSCs infused on SCI rats. The increase of inflammatory cytokines was repressed in hUC-MSCs ITH-H group. Our results confirmed that hUC-MSC administered via intrathecal injection has dose-dependent neuroprotection effect in SCI rats.

Knockdown of circAPLP2 Inhibits Progression of Colorectal Cancer by Regulating miR-485-5p/FOXK1 Axis.

Background: Circular RNAs (circRNAs) have recently been reported to play essential roles in the progression of various cancers, including colorectal cancer (CRC). However, the roles of circRNA amyloid precursor-like protein 2 (circAPLP2) in CRC and its underlying mechanism have not been investigated. Materials and Methods: The expression levels of circAPLP2, microRNA-485-5p (miR-485-5p), and forkhead-box K1 (FOXK1) were determined by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion were assessed by methylthiazolyldiphenyl-tetrazolium bromide assay, flow cytometry, and transwell assay, respectively. Western blot assay was performed to measure the protein levels of proliferating cell nuclear antigen, Bcl-2, Bax, vimentin, E-cadherin, fibronectin, and FOXK1. The interaction between miR-485-5p and circAPLP2 or FOXK1 was predicted by starBase and verified by dual-luciferase reporter assay. A xenograft tumor model was established to confirm the functions of circAPLP2 in vivo. The lactate production was measured using lactate assay kit. Results: circAPLP2 expression was enhanced in CRC tissues and cells. circAPLP2 knockdown or miR-485-5p overexpression suppressed cell proliferation, migration, and invasion, whereas it promoted apoptosis in CRC cells, which was reversed by upregulating FOXK1. Moreover, miR-485-5p could directly bind to circAPLP2 and its downregulation reversed the suppressive effect of circAPLP2 knockdown on progression of CRC cells. In addition, FOXK1 was a downstream target of miR-485-5p. Furthermore, circAPLP2 modulated FOXK1 expression by sponging miR-485-5p in CRC cells. Besides, interference of circAPLP2 suppressed tumor growth in vivo and inhibited glycolysis in vitro by upregulating miR-485-5p and downregulating FOXK1. Conclusions: circAPLP2 knockdown inhibited CRC progression through regulating miR-485-5p/FOXK1 axis, providing a novel avenue for treatment of CRC.

Risk Potential for Organ Dysfunction Associated With Sodium Bicarbonate Therapy in Critically Ill Patients With Hemodynamic Worsening.

Background: The role of sodium bicarbonate therapy (SBT) remains controversial. This study aimed to investigate whether hemodynamic status before SBT contributed to the heterogeneous outcomes associated with SBT in acute critically ill patients. Methods: We obtained data from patients with metabolic acidosis from the Medical Information Mart for Intensive Care (MIMIC)-III database. Propensity score matching (PSM) was applied to match the SBT group with the control group. Logistic regression and Cox regression were used to analyze a composite of newly "developed or exacerbated organ dysfunction" (d/eOD) within 7 days of ICU admission and 28-day mortality associated with SBT for metabolic acidosis. Results: A total of 1,765 patients with metabolic acidosis were enrolled, and 332 pairs obtained by PSM were applied to the final analyses in the study. An increased incidence of newly d/eOD was observed in the SB group compared with the control group (54.8 vs. 44.6%, p < 0.01). Multivariable logistic regression indicated that the adjusted OR of SBT for this composite outcome was no longer significant [OR (95% CI): 1.39 (0.9, 1.85); p = 0.164]. This effect of SBT did not change with the quintiles stratified by pH. Interestingly, SBT was associated with an increased risk of the composite of newly d/eOD in the subgroup of patients with worsening hemodynamics before SBT [adjusted OR (95% CI): 3.6 (1.84, 7.22), p < 0.001]. Moreover, the risk potential for this composite of outcomes was significantly increased in patients characterized by both worsening [adjusted OR (95% CI): 2.91 (1.54, 5.47), p < 0.001] and unchanged hemodynamics [adjusted OR (95% CI): 1.94 (1.01, 3.72), p = 0.046] compared to patients with improved hemodynamics before SBT. Our study failed to demonstrate an association between SBT and 28-day mortality in acute critically ill patients with metabolic acidosis. Conclusions: Our findings did not demonstrate an association between SBT and outcomes in critically ill patients with metabolic acidosis. However, patients with either worsening or unchanged hemodynamic status in initial resuscitation had a significantly higher risk potential of newly d/eOD subsequent to SBT.