•A strategy for in situ metabolically synthesized active drug-based probes was proposed.•The potential purgative targets of SA were successfully hooked and identified.•The work provided a new insight for studying the direct targets of unstable active drugs.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Wastewater-based epidemiology(WBE)can effectively assess population health status,but it is lack of analytical methods which can simultaneously analyze a number of pharmaceuticals and biomarkers in wastewater.In this work,a method including sample pretreatment and instrumental detection for quantifying 83 kinds of pharmaceuticals and biomarkers in the influent of wastewater treatment plants(WWTPs)was established by sing solid phase extraction-ultra performance liquid chromatography-tandem mass spectrometry(SPE-UPLC-MS/MS).The water sample(200 mL)with 83 kinds of target compounds was divided into two aliquots,which were then enriched and purified using HLB columns at pH=6.7 and pH=2 respectively,followed by elution with 6 mL of methanol and 6 mL of methanol containing 2%(V/V)formic acid,respectively,and then dried by nitrogen blown,concentrated,and finally redissolved to 0.5 mL,filtered through a nylon filter(0.22 μm).The target compounds in the samples were determined using UPLC-MS/MS in electrospray ionization under both positive and negative ion multiple reaction monitoring modes,with quantification using the internal standard method.The method exhibited good linearity(r>0.996)for the 83 kinds of target compounds in the concentration range of 0.1-500 ng/mL,and intra-day and inter-day precisions were 1.2%-16.5%.The recoveries of target substances in pure water and influent samples from a WWTP were 51.6%-166.6%and 56.4%-150.1%,respectively,with relative standard deviations of 0.2%-31.9%and 0.3%-20.9%,respectively.The method detection limits of target compounds were 0.02-7.72 ng/L.This method was applied to determine pharmaceuticals and biomarkers in the influent samples of a WWTP in Guangzhou,and 54 kinds of pharmaceuticals and 4 kinds of biomarkers were detected.The concentrations of acetaminophen and erythromycin were the highest among the pharmaceuticals,1.6-3.4 μg/L and 0.6-1.1 μg/L,respectively.The concentration of caffeine was the highest among the biomarkers,i.e.,33.3-43.9 μg/L.This method had high sensitivity,good stability and accuracy,and was suitable for detection of pharmaceuticals and biomarkers in the influent of WWTP,which could provide analytical method support for conducting studies on WBE.

Objective To investigate the mechanism of melezitose(MELE)on ulcerative colitis(UC)by structing a mouse model of ulcerative colitis(UC)induced by dextran sodium sulfate(DSS).Methods Forty-eight SPF grade male c57BL/6 mice were randomly divided into normal group(0.9％NaCl),model group(0.9％NaCl),control group(100 mg·kg-1 mesalazine)and experimental-L,-M,-H groups(20,40,80 mg·kg-1 melezitose solution).The UC model was induced by giving 3％DSS solution instead of drinking water,and the disease activity index(DAI)was evaluated.Serum levels of interleukin-1 β(IL-113),IL-6,IL-10 and tumor necrosis factor α(TNF-α)were detected by enzyme linked immunosorbent assay.The expression levels of major histocompatibility complex Ⅱ(MHC Ⅱ)and cluster of differentiation 4 receptors(CD4)protein were detected by Western blot.Results The levels of IL-1 β in serum in the experimental-M,-H groups,model group and normal group were(82.15±13.66),(75.56±11.07),(118.20±19.31)and(23.47±4.72)pg·mL-1;serum IL-6 levels were(71.54±16.48),(58.57±15.62),(140.60±5.76)and(30.33±4.15)pg·mL-1;serum IL-10 levels were(48.64±5.60),(52.65±7.99),(27.10±4.91)and(61.90±10.44)pg·mL-1;serum TNF-α levels were(70.33±8.51),(66.55±8.12),(90.88±4.90)and(34.18±4.15)pg·mL-1;the relative expression levels of MHC Ⅱ protein were 0.34±0.04,0.15±0.06,0.08±0.05 and 0.53±0.59;the relative expression levels of CD4 protein were 0.79±0.08,0.92±0.12,0.99±0.11 and 0.54±0.14,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups showed statistically significant differences(P＜0.05,P＜0.01).Conclusion Melezitose could effectively improve the symptoms of UC mice;the mechanism may be through down-regulating MHC Ⅱ protein and up-regulating CD4 protein to activate T cell signal pathway to play an anti-inflammatory effect.

Objective: To explore the changes in bacterial community structure, antibiotic resistance genome, and pathogen virulence genome in river water before and after the river flowing through Haikou City and their transmission and dispersal patterns and to reveal anthropogenic disturbance's effects on microorganisms and resistance genes in the aquatic environment. Methods: The Nandu River was divided into three study areas: the front, middle and rear sections from the upstream before it flowed through Haikou City to the estuary. Three sampling sites were selected in each area, and six copies of the sample were collected in parallel at each site and mixed for 3 L per sample. Microbial community structure, antibiotic resistance, virulence factors, and mobile genetic elements were analyzed through bioinformatic data obtained by metagenomic sequencing and full-length sequencing of 16S rRNA genes. Variations in the distribution of bacterial communities between samples and correlation of transmission patterns were analyzed by principal co-ordinates analysis, procrustes analysis, and Mantel test. Results: As the river flowed through Haikou City, microbes' alpha diversity gradually decreased. Among them, Proteobacteria dominates in the bacterial community in the front, middle, and rear sections, and the relative abundance of Proteobacteria in the middle and rear sections was higher than that in the front segment. The diversity and abundance of antibiotic resistance genes, virulence factors, and mobile genetic elements were all at low levels in the front section and all increased significantly after flow through Haikou City. At the same time, horizontal transmission mediated by mobile genetic elements played a more significant role in the spread of antibiotic-resistance genes and virulence factors. Conclusions: Urbanization significantly impacts river bacteria and the resistance genes, virulence factors, and mobile genetic elements they carry. The Nandu River in Haikou flows through the city, receiving antibiotic-resistant and pathogen-associated bacteria excreted by the population. In contrast, antibiotic-resistant genes and virulence factors are enriched in bacteria, which indicates a threat to environmental health and public health. Comparison of river microbiomes and antibiotic resistance genomes before and after flow through cities is a valuable early warning indicator for monitoring the spread of antibiotic resistance.
Humans ; Rivers ; Virulence Factors/genetics* ; RNA, Ribosomal, 16S/genetics* ; Microbiota/genetics* ; Anti-Bacterial Agents ; Drug Resistance, Microbial/genetics*

Five new flavonoid derivatives, cajavolubones A-E (1-5), along with six known analogues (6-11) were isolated from Cajanus volubilis, and their structures were elucidated by spectroscopic analysis and quantum chemical calculations. Cajavolubones A and B (1 and 2) were identified as two geranylated chalcones. Cajavolubone C (3) was a prenylated flavone, while cajavolubones D and E (4 and 5) were two prenylated isoflavanones. Compounds 3, 8, 9 and 11 displayed cytotoxicity against HCT-116 cancer cell line.
Flavonoids/chemistry* ; Cajanus ; Molecular Structure ; Chalcones/chemistry*

Objective:To investigate the significance of serum fibroblast growth factor 19 (FGF19), Klotho and fibroblast growth factor receptor 4 (FGFR4) protein expression in patients with primary biliary cirrhosis (PBC).Methods:Sixty-three patients with PBC who received treatment in Ningbo Huamei Hospital, University of Chinese Academy of Sciences between August 2017 and July 2020 were included in the PBC group. An additional 51 healthy patients who concurrently received physical examination in the same hospital were included in the control group. Serum FGF19, Klotho and FGFR4 protein expression were determined by enzyme linked immunosorbent assay.Results:Serum FGF19 and FGFR4 protein in PBC group were (178.86 ± 21.28) ng/L and (2.96 ± 0.47) ng/L, respectively, which were significantly higher than those in the control group [(69.93 ± 12.12) ng/L, (1.21 ± 0.35) ng/L, t = 32.51, 27.98, both P < 0.05]. Klotho protein expression in the PBC group was significantly lower than that in the control group [(3.25 ± 0.89) μg/L vs. (9.67 ± 1.53) μg/L, t = 22.08, P < 0.05]. Serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase in the PBC group were (84.25 ± 13.24) U/L, (71.82 ± 10.35) U/L, (278.93 ± 32.45) U/L, respectively, which were significantly higher than those in the control group [(23.76 ± 3.42) U/L, (23.10 ± 4.53) U/L, (76.81 ± 16.36) U/L, t = 31.75, 31.26, 40.48, all P < 0.05]. The receiver operating characteristic curve analysis showed that the sensitivity and specificity of FGF19 in the diagnosis of PBC were 76.67% and 61.90%, respectively, they were 58.82% and 66.67% for Klotho protein diagnosis, 54.55% and 76.67% for FGFR4 protein. Pearson analysis revealed that there was a positive linear relationship between FGF19 and FGFR4 protein ( r = 0.78, P < 0.05), while there was a negative linear relationship between Klotho protein and FGFR4 protein ( r = -0.72, P < 0.05). Conclusion:In patients with PBC, serum FGF19 and FGFR4 protein levels are increased, while Klotho protein level is decreased. There is a positive linear relationship between FGF19 and FGFR4 protein, and there is a negative linear relationship between Klotho protein and FGFR4 protein. This study is highly innovative and scientific.

Objective: To analyze the short-term efficacy of sleeve gastrectomy plus uncut jejunojejunostomy (SG+uncut JJB) for patients with obesity. Methods: This prospective study was conducted in the General Surgery Department of Beijing Chaoyang Hospital from January to December 2020 (NCT04534504). The inclusion criteria were patients with a body mass index (BMI) of >32.5 kg/m², type 2 diabetes mellitus (T2DM) or at least two comorbidities with a BMI of 27.5-32.5 kg/m², a waist circumference of >90 cm (male) or >85 cm (female), and those aged between 16 and 65 years. The exclusion criteria included patients who were pregnant, diagnosed with severe neurological or mental illnesses, long-term users of antidepressants and immunosuppressants, and diagnosed with severe gastroesophageal reflux disease or underwent revision surgery. Patients with incomplete follow-up data or insufficient follow-up time were also excluded. Patients were divided into SG-uncut JJB group and SG group according to doctor's recommendation and patients' wills. The primary endpoint was the percentage of excess weight loss (%EWL), and the secondary endpoints were the percentage of total weight loss (%TWL) and the T2DM remission rate. All patients were regularly followed up until the end of December 2020. Results: After excluding seven patients who did not meet the inclusion criteria, 47 eligible patients were finally identified, with 21 in the SG+uncut JJB group and 26 in the SG group. The operation time (140 [110-180] minutes vs. 90 [70-180] minutes, Z=-3.642, P=0.001) and total cost ([54,000 ± 6000] yuan vs. [49,000 ± 7000] yuan, t=2.590, P=0.013) were slightly higher in the SG+uncut JJB group than in the SG group (all P<0.05). However, no significant differences were observed in terms of postoperative hospital stay, operative blood loss, and postoperative complications between the two groups (all P>0.05). The incidence of nausea and vomiting was significantly lower in the SG+uncut JJB group than in the SG group (9.5% [2/21] vs. 46.2% [12/26], χ²=7.453, P=0.006}. The %EWL and %TWL in the SG+uncut JJB group tended to increase gradually with time. The same trend was also observed in the SG group during the first 6 months of follow-up. The 12-month %EWL and %TWL in the SG group were slightly lower compared with the 6-month %EWL and %TWL (P=0.001). The 12-month %EWL values in the SG+uncut JJB and SG groups were (72.4%±12.3%) and (63.6%±25.7%), respectively. However, no significant differences were observed between the two groups in terms of %EWL. Moreover, the 1-month ([11.1%±2.4%] vs. [8.2%±4.4%], P=0.011) and 12-month %TWL ([29.7%±6.9%] vs. [20.3%±7.2%], P=0.001) were significantly higher in the SG+uncut JJB group than in the SG group. No significant differences were observed in terms of T2DM and hypertension remission (all P>0.05). Conclusion: SG+uncut JJB might achieve a promising weight-loss effect similar to SG with a relatively lower incidence of postoperative nausea and vomiting, and it might be an effective and safe approach for obesity management.
Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Diabetes Mellitus, Type 2/surgery* ; Gastrectomy ; Gastric Bypass ; Immunosuppressive Agents ; Laparoscopy ; Obesity/surgery* ; Obesity, Morbid/surgery* ; Prospective Studies ; Retrospective Studies ; Treatment Outcome ; Weight Loss

Objective:To re-evaluate the intervention effect of Kuijietong（KJT） on ulcerative colitis（UC）. Method:Sixty patients with mild-to-moderate UC in the active stage were enrolled and randomized into a KJT group （n=30） and a sulfasalazine （SASP） group （n=30）. Patients in the KJT group were treated with KJT granules， one bag divided in two daily doses， once in the morning and once in the evening， while those in the SASP group received SASP， 1 g per time， four times per day. Then the clinical efficacy was evaluated. Result:According to the modified Mayo score，the clinical remission rates of the KJT group and SASP group were determined to be 46.7% （14/30）and 40% （12/30），exhibiting no significant difference between the two groups （P>0.05）. The clinical effective rate of the KJT group was 83.3% （25/30），which was better than 60% （18/30） of the SASP group （P<0.05）. The mucosal healing rate in the KJT group was 36.7% （11/30）， not significantly different from 30% （9/30） in the SASP group. In the alleviation of UC symptoms，the score of large intestine dampness heat syndrome in the KJT group was remarkably better than that in the SASP group （P<0.05），but there was no significant difference in inflammatory bowel disease questionnaire （IBDQ） score between the two groups. In terms of physical and chemical indexes，serum erythrocyte sedimentation rate （ESR） in the KJT group after intervention was lower than that in the SASP group （P<0.05），whereas the interleukin-10 （IL-10） level was higher（P<0.05）. The comparison between the two groups revealed no significant difference in C-reactive protein （CRP）， tumor necrosis factor-α （TNF-α）， CD4⁺ T cells and regulatory T （Treg） cells after intervention. During the intervention，no obvious adverse reactions were found in the two groups，indicating good safety. Conclusion:KJT is not inferior to SASP in relieving mild-to-moderate UC in the active stage.