Objective:To evaluate the potential value of gut microbiota metabolites in predicting the efficacy of neoadjuvant chemoradiotherapy combined with immunotherapy in patients with locally advanced rectal cancer.Methods:Prospectively collected case data from 32 patients with locally advanced rectal patients, who underwent total mesorectal excision at Beijing Friendship Hospital, Capital Medical University, between October 2021 and August 2022. Among these patients, 18 (56.25%) were male and 14 (43.75%) were female, with ages ranging from 37 to 79 years and a mean age of (61.69±8.73) years. Postoperative pathological response was evaluated using the Tumor Regression Grade (TRG), dividing the patients into two groups: an efficacious group (ypT 0N 0, n=14) and a non-efficacious group (non-ypT 0N 0, n=18). Stools from 14 patients in the efficacious group and 18 patients in the non-efficacious group, who had experienced neoadjuvant chemoradiotherapy combined with immunotherapy, were collected before treatment. Metabolites were analyzed using high-performance liquid chromatography-tandem mass spectrometry, and pathway enrichment analysis was performed. A random forest model was constructed based on the differential metabolites. The data were analyzed by using R4.1.1 and 26.0 software. Results:Through untargeted metabolomics analysis, 2′-Deoxyinosine and albiflorin were enriched in the responders, while Sorbitan monooleate, 2-(Formylamino) Benzoic Acid, and 12-Hydroxydodecanoic acid were enriched in the non-responders ( P<0.05); Arachidonic acid metabolism and tryptophan metabolism were enriched, and the AUC for the model was 0.976. Conclusions:Rectal cancer patients with or without complete postoperative pathological remission exhibit differences in the metabolites of their intestinal microbiome prior to undergoing neoadjuvant chemoradiotherapy combined with immunotherapy. The identified differential metabolites have the potential to serve as predictive biomarkers for treatment efficacy.

Objective:To investigate the current application of blood purification in the treatment of acute poisoning within Jiangsu Province and to evaluate the impact of extracorporeal blood purification on the clinical outcomes of critically poisoned patients.Methods:This multicenter, cross-sectional real-world observational study followed patients presenting with poisoning to the emergency departments of nine hospitals in Jiangsu Province between June 2015 and May 2019. Data were collected on demographic characteristics, vital signs within the first hour of emergency presentation, treatment modalities, length of hospital stay, and survival outcomes. Clinical data from patients who underwent extracorporeal blood purification were compared with those who did not, using the Wilcoxon rank-sum test and Chi-square test.Results:A total of 4 178 poisoning cases were included between June 2015 and May 2019. Among them, 21.7% (908/4 178) received blood purification therapy, while 78.3% (3 270/4 178) did not. Hemoperfusion (90.4%) was the most frequently employed method, followed by continuous renal replacement therapy (CRRT) (4.4%). In combined blood purification modalities, 4.8% underwent hemoperfusion combined with CRRT, 0.1% received hemoperfusion with plasma exchange, and another 0.1% underwent hemoperfusion combined with both CRRT and plasma exchange. Among patients who underwent blood purification, pesticide poisoning was the most prevalent (76.3%), with the most common toxic agents being paraquat (23.7%), dichlorvos (8.7%), methamidophos (5.2%), omethoate (4.0%), and glyphosate (3.7%). Compared to the non-blood purification group, patients in the blood purification group were more likely to present within the first hour with a low Glasgow Coma Scale (GCS) score (3-8) (22.6% vs. 9.7%, P <0.05), low mean arterial pressure (8.0% vs. 3.2%, P <0.05), longer hospital stays [5(3,9) days vs. 2(1,4) days, P <0.05] and a higher in-hospital mortality rate (21.1% vs. 5.3%, P <0.05). Follow-up via telephone 28 days after discharge revealed a survival rate of 78.9%, with a mortality rate of 21.1% in the blood purification group. Conclusions:Hemoperfusion is the most commonly utilized blood purification technique for treating poisoning in Jiangsu Province, with pesticides being the primary toxic agents treated. Although the mortality rate is higher in the blood purification group, the intervention may still contribute to improved patient outcomes.

It is believed that wind pathogen is one of the core pathogenic factors of small cell lung cancer （SCLC）. The nature and pathogenic characteristics of wind pathogen are closely related to the occurrence and metastasis of SCLC. Mainly manifested as deficiency of both qi and yin， healthy qi deficiency of SCLC makes it susceptible to invasion of external wind. Simultaneously， there are internal wind pathogenesis such as yin deficiency causing wind， blood deficiency causing wind， phlegm， stasis and toxin causing wind， liver yang transforming into wind. The internal and external winds together lead to the disease. Therefore， it is proposed to treat SCLC from wind theory， that is， boosting qi and nourishing yin to extinguish wind with taizishen （Radix Pseudostellariae）， wuweizi （Fructus Schisandrae Chinensis） and others； resolving phlegm and moving stasis to dispel wind with wind-dispelling and phlegm-resolving medicinals such as jiangcan （Bombyx Batryticatus）， muhudie （Semen Oroxyli）， fangfeng （Radix Saposhnikoviae）， tianma （Rhizoma Gastrodiae）， quanxie （Scorpio） and blood-invigorating and wind-dispelling medi-cinals such as danggui （Radix Angelicae Sinensis）， chuanxiong （Rhizoma Chuanxiong） and danshen （Radix et Rhizoma Salviae Miltiorrhizae）； attacking toxin and dissipating masses to dispel wind with shuizhi （Hirudo）， dilong （Pheretima）， fengfang （Nidus Vespae）， quanxie， baihuashe （Agkistrodon）， jiuxiangchong （Aspongopus） and other drastic medicinals； calming liver and extinguishing wind to prevent brain metastasis of SCLC with Tianma Gouteng Beverage （天麻钩藤饮） modification.

Objective To explore the molecular mechanism of Xiaojin Pills in the treatment of breast cancer using an integrated network pharmacology and experimental verification.Methods The chemical components and potential targets of Xiaojin Pills were obtained from TCMSP,TCM-ID,ETCM and SwissTargetPrediction databases.Breast cancer related targets were collected from GeneCards,OMIM and KEGG databases.The overlapped targets were imported into STRING database to analysis a protein-protein interaction(PPI).The key targets of PPI networks were screened based on node topology parameter values through Cytoscape 3.8.0.DAVID database was used to analyze the GO and KEGG pathway enrichment to build drug-chemical components-key targets-signaling pathway network.The breast cancer cell lines MDA-MB-231 and SK-BR-3 were used to study the effects of Xiaojin Pills extract on cell apoptosis,migration and invasion,and to verify the key pathway obtained by enrichment analysis.Results Totally 181 chemical components in Xiaojin Pills were obtained,including quercetin,myricetin,pinocembrin and β-sitosterol.615 potential targets were identified for the anti-breast cancer effects of Xiaojin Pills.After overlapping,170 key targets against breast cancer were identified based on the topological analysis,which included SRC,ERK1/2,AKT1,EGFR,etc.KEGG analysis enriched pathways including pathways in cancer,MAPK signaling pathway,endocrine resistance,PI3K-AKT signaling pathway,EGFR tyrosine kinase inhibitor resistance,apoptosis,and HIF-1 signaling pathway,which may play important roles in the therapeutic effects of Xiaojin Pills against breast cancer.GO enrichment was involved in protein phosphorylation,inflammatory response,negative regulation of apoptosis,and positive regulation of ERK1 and ERK2 cascades.Cell experiments showed that Xiaojin Pills further induced mitochondria-dependent apoptosis by inhibiting the activation of MAPK and PI3K-AKT pathways.At the same time,the expressions of ZO-1 and β-catenin increased,and the epithelial-mesenchymal transformation process was reversed to inhibit the metastasis of breast cancer cells.Conclusion The key targets and signaling pathways of Xiaojin Pills in the treatment of breast cancer are studied through network pharmacology combined with in vitro experiments,which provided a basis for further study of its pharmacodynamic material basis,mechanism of action and clinical application.

Objective:To investigate the prospective association of sleep duration with the development of chronic obstructive pulmonary disease (COPD) in adults in Suzhou.Methods:The study used the data of 53 269 participants aged 30-79 years recruited in the baseline survey from 2004 to 2008 and the follow-up until December 31, 2017 of China Kadoorie Biobank (CKB) conducted in Wuzhong District, Suzhou. After excluding participants with airflow limitation, self-reported chronic bronchitis/emphysema/coronary heart disease history at the baseline survey and abnormal or incomplete data, a total of 45 336 participants were included in the final analysis. The association between daily sleep duration and the risk for developing COPD was analyzed by using a Cox proportional hazard regression model, and the hazard ratio ( HR) values and their 95% CI were calculated. The analysis was stratified by age, gender and lifestyle factors, and cross-analysis was conducted according to smoking status and daily sleep duration. Results:The median follow-up time was 11.12 years, with a total of 515 COPD diagnoses in the follow-up. After adjusting for potential confounders, multifactorial Cox proportional hazard regression analysis showed that daily sleep duration ≥10 hours was associated with higher risk for developing COPD ( HR=1.42, 95% CI: 1.03-1.97). The cross analysis showed that excessive daily sleep duration increased the risk for COPD in smokers ( HR=2.49, 95% CI: 1.35-4.59, interaction P<0.001). Conclusion:Longer daily sleep duration (≥10 hours) might increase the risk for COPD in adults in Suzhou, especially in smokers.

Liver transplantation is an effective treatment for end-stage liver disease in children,and its clinical efficacy has been validated.Split liver transplantation(SLT)can effectively expand the donor liver pool for children.SLT for children has unique clinical characteristics and principles.Establishing technical operation specifications for pediatric SLT plays a significant role in improving clinical efficacy.In this paper,clinical practice guidelines on pediatric SLT were established in the aspect of donor and donor liver evaluation,donor-recipient matching,and ductal segmentation and reconstruction of donor liver,aiming to standardize the technical process,optimize surgical operational details,minimize the risk of com-plications of SLT for children,further promoting the rapid development of pediatric SLT in China.

Objective:To evaluate the effect of intraoperative cell salvage (ICS) on the number and viability of cancer cells in salvaged autologous blood from the patients undergoing liver cancer surgery.Methods:Twenty patients undergoing open radical primary hepatocellular carcinoma were selected, and blood from the operative field was collected after exposing the liver and treated with ICS. Blood specimens 20 ml from the surgical field (S 1), blood specimens 20 ml before ICS treatment-leukocyte depletion filter (LDF) filtration (S 2) and blood specimens 20 ml after LDF filtration (S 3) were collected and enriched, of which the blood sample 10 ml was used for cancer cell identification and count by immunofluorescence staining, and the remaining blood sample 10 ml was continuously cultured for 3 weeks, and then cell viability was observed by immunofluorescence method. Results:Hepatocellular carcinoma(HCC) cells were identified in 19 S 1 specimens, 18 S 2 specimens, and 16 S 3 specimens, but there was no significant difference in the detection rate among the three specimens ( P>0.05). Compared with S 1 specimens, HCC cell count was significantly reduced in S 2 and S 3 specimens ( P<0.05). There was no significant difference in the HCC cell count between S 3 specimens and S 2 specimens ( P>0.05). After 3 weeks of culture, the results of light microscopy showed that: hepatocellular carcinoma cell clusters were found in S1 specimens, and no hepatocellular carcinoma cell cluster was found in S 2 and S 3 specimens; the results of fluorescence microscopy showed that: 400 and 14 mixed epithelial-mesenchymal HCC cells and 100 and 21 mesenchymal HCC cells were found in S 1 and S 2 specimens, respectively, while no HCC cells were identified in S 3 specimens, among which HCC cells mainly presented as clusters of hepatocellular carcinoma cells in S 1 specimen, while no clusters of hepatocellular carcinoma cells were found in S 2 and S 3 specimens. Conclusions:After treatment with ICS or ICS-LDF, the number and viability of hepatocellular carcinoma cells in salvaged autologous blood are significantly reduced, and hepatocellular carcinoma cells exist as single cells and fail to develop clusters of hepatocellular carcinoma cells; LDF can reduce the risk of hepatocellular carcinoma cell autotransfusion to a certain extent, although it can not effectively filter out hepatocellular carcinoma cells continuously.

Objective:This work aims to investigate the virulence features, spore formation and the resistance mechanisms of major sequence types (STs) of clinical Clostridium difficile isolates from nosocomial infectious diarrhea. Methods:Clostridium difficile isolates were prospectively collected from 816 loose stool samples of in patients with antibiotic associated diarrhea at the Beijing Friendship Hospital of Capital Medical University from September 2017 to September 2019. The main ST types ST81 (26 strains), ST8 (15 strains) and ST42 (14 strains) of C. difficile were used as experimental strains. The polymerase chain reaction (PCR) and enzyme-linked immunoassay (ELISA) were performed to detect toxin genes and toxin production of different C. difficile ST types, respectively. The count of the colony forming units (CFU) of the strains as conducted by using the brain-heart infusion (BHI) agar plates. The antimicrobial resistance patterns of the strains to eleven kinds of antibiotics were determined by agar dilution method. The antimicrobial resistance genes: gyrA, gyrB and ermB were amplified and sequenced from the stains. Mutations in the resistance genes were analyzed by sequencing. Measure data was compared by Kruskal Wallis Test, differences in the resistance rates in three group were compared using Fisher exact test. Results:ST81 strains were identified as the tcdA-tcdB+/ cdtA-cdtB-toxin type, ST8 and ST42 strains belonged to tcdA+tcdB+/ cdtA-cdtB-toxin type. The toxin production of ST42 strains (41.9) were higher than ST8 (2.4) and ST81 groups (0.83) (all P<0.001). The number of spore quantities of ST81, ST8 and ST42 strains were 494×10 5CFU/ml, 160×10 5CFU/ml and 166×10 5CFU/ml, respectively. The spore quantities of ST81 strains were much higher than that of ST81 and ST42 strains (all P<0.001). From the in vitro susceptibility test, 100% (26/26) ST81 strains were featured as multi-drug resistant (MDR), and they were resistant to moxifloxacin, ceftriaxone, erythromycin and clindamycin. The resistance rates of ST8 strain to moxifloxacin, erythromycin and clindamycin were 9/15, 11/15 and 11/15, respectively. ST81 strains had higher resistance rates to moxifloxacin, clindamycin and erythromycin, compared to ST8 strains ( P=0.001, P=0.005 and P=0.005). All ST42 strains were susceptible to ceftriaxone and 3/14 ST42 strains were resistant to moxifloxacin. ST81 strains had higher resistance rates to ceftriaxone and moxifloxacin than the ST42 strains (both P<0.001). The positive rate of ermB in ST81 strains (100%, 26/26) were higher the ST8 strains (11/15) ( P<0.005). Amino acid mutation analysis showed that ST81and ST8 stains had one amino acid substitution in both GyrA and GyrB, but the amino acid substitutions were different in GyrB between two ST types. ST81 strains had two point-mutations: Thr82 replaced by Ile in GyrA, and Asp426 replaced by Val in GyrB. ST8 strains had point-mutation: Thr82 replaced by Ile in GyrA; Asp426 replaced by Asn in GyrB. For ST42 strains, Thr82 was replaced by Ile in GyrA. Conclusions:ST81 and ST42 strains were MDR. ST81 had higher spore ability, whereas ST42 strains had more virulence. ST81 strains and most of ST8 strains had high level of fluoroquinolones resistance. It is important to supervise persistently these three ST genotypes to prevent further dissemination.

ObjectiveTo study the mechanism of Shenbai Jiedu prescription inhibiting the proliferation of HCT116 colorectal cancer （CRC） cells by regulating the phosphatase and tensin homolog deleted on chromosome ten （PTEN）/phosphatidylinositol 3-kinase （PI3K）/ protein kinase B （Akt） signaling pathway. MethodShenbai Jiedu prescription was extracted by water extraction and alcohol precipitation to prepare freeze-dried powder. HCT116 cells were cultured in vitro， and treated with different concentrations of Shenbai Jiedu prescription （2， 4， 8， 16 g·L^-1）. The inhibitory effect of Shenbai Jiedu prescription on the proliferation of HCT116 cells was tested by methyl thiazolyl tetrazolium （MTT）. Real-time quantitative PCR was used to detect the mRNA expression levels of PTEN， PI3K， Akt， glycogen synthase kinase-3β （GSK-3β）， c-Myc， survivin and Cyclin D₁. Western blot was employed to measure the protein expression levels of PTEN， phosphorylated PTEN （p-PTEN）， PI3K， Akt， phosphorylated Akt （p-Akt）， GSK-3β， phosphorylated GSK-3β （p-GSK-3β）， c-Myc， survivin and Cyclin D₁， β-catenin nuclear import was explored by immunofluorescence assay. ResultCompared with the control group， Shenbai Jiedu prescription inhibited the proliferation of HCT116 cells in a dose-dependent manner （P<0.01）. Compared with the control group， the mRNA expression levels of PTEN and GSK-3β were up-regulated whereas those of PI3K， Akt， c-Myc， survivin and CyclinD₁ were down-regulated after treatment with Shenbai Jiedu prescription （P<0.01）. The protein expression levels of PTEN， p-PTEN and GSK-3β were up-regulated whereas those of PI3K， Akt， p-Akt， GSK-3β， p-GSK-3β， c-Myc， survivin and CyclinD₁ were down-regulated （P<0.05， P<0.01）. Immunofluorescence assay showed that Shenbai Jiedu prescription suppressed β-catenin nuclear import in HCT116 cells. ConclusionShenbai Jiedu prescription inhibited the proliferation of HCT116 cells via the mechanism of regulating the PTEN/PI3K/Akt signaling pathway.