Mechanism of intestinal injury induced by acute diquat poisoning in rats / 中华危重病急救医学

Objective:To investigate the effects of diquat (DQ) on the expression of intestinal pyroptosis-related proteins and tight junction proteins in rats, and to analyze the role of pyroptosis in the intestinal injury of rats with acute DQ poisoning.Methods:A total of 36 Wistar male rats were randomly divided into control group, and 3 hours, 12 hours, 36 hours and 3 days exposure groups, with 6 rats in each group. Each exposure group was given 1/2 median lethal dose (LD50) of 115.5 mg/kg DQ by one-time gavage. The control group was given the same amount of normal saline by gavage. The control group was anesthetized at 3 hours after DQ gavage to take jejunal tissues; each exposure group was anesthetized at 3 hours, 12 hours, 36 hours, and 3 days after DQ gavage to take jejunal tissues, respectively. The general conditions of the rats were recorded. The pathological changes of jejunum tissue were observed by hematoxylin-eosin (HE) staining. The expression of intestinal pyroptosis-related proteins [NOD-like receptor protein 3 (NLRP3), cysteine aspartate-specific protease 1 (caspase-1), Gasdemin D (GSDMD)] in the intestinal tissues was observed by immunohistochemical staining. Western blotting was used to detect the expression of intestinal pyroptosis-related proteins and intestinal tight junction proteins (Occludin and Claudin-1).Results:Light microscopy showed that pathological changes occurred in jejunum tissue at the early stage of exposure (3 hours), and the injury was the most serious in the 12 hours exposure group, with a large number of inflammatory cells infiltrating in the tissue, and the damage was significantly reduced after 3 days exposure. Immunohistochemical results showed that NLRP3, caspase-1 and GSDMD were expressed in the jejunal mucosa of the control group and the exposure groups, and the positive cells in the control group were less expressed with light staining. The expression of the above proteins in the exposed group was increased significantly and the staining was deep. Western blotting results showed that compared with the control group, the expression of NLRP3 protein in jejunum tissues of all groups was increased, with the most significant increase in the 36 hours group (NLRP3/β-actin: 1.47±0.06 vs. 0.43±0.14, P < 0.01). Compared with the control group, the expression of GSDMD protein in the 3 hours, 12 hours and 36 hours exposure groups increased, and the expression of GSDMD protein in the 3 hours and 12 hours exposure groups increased significantly (GSDMD/β-actin: 1.04±0.40, 1.25±0.15 vs. 0.65±0.25, both P < 0.05). The expression of caspase-1 protein was increased in 36 hours exposure group compared with the control group (caspase-1/β-actin: 1.44±0.34 vs. 0.98±0.19, P > 0.05). Compared with the control group, the expression of Occludin and Claudin-1 proteins in each exposure group decreased, and the expression of Occludin proteins was significantly decreased in the 3 hours, 12 hours, and 36 hours exposure groups decreased significantly (Occludin/β-actin: 0.74±0.17, 0.91±0.20, 0.79±0.23 vs. 1.41±0.08, all P < 0.05). Although the protein expression of Claudin-1 decreased in each exposure group, the difference was not statistically significant. Conclusion:The intestinal injury caused by acute DQ poisoning may be related to the activation of pyroptosis pathway of small intestinal cells and the reduction of the density of intercellular junctions.

Adjustable external fixation traction combined with arthroscopic microfracture for treatment of osteochondral lesions of the talus / 中华创伤骨科杂志

Objective:To investigate the clinical effects of adjustable external fixation traction combined with arthroscopic microfracture in the treatment of osteochondral lesions of the talus (OLT).Methods:A retrospective study was conducted to analyze the data of 27 OLT patients who had been treated at Department of Orthopedics, Beijing Rehabilitation Hospital from May 2017 to March 2022. There were 16 males and 11 females, aged (32.4±7.2) years. Lesion site: 23 medial and 4 lateral cases; Hepple staging: 7 cases at stage Ⅰ, 15 cases at stage Ⅱ, and 5 cases at stage Ⅲ; disease duration: (10.6±3.3) months. All the patients were treated by adjustable external fixation traction combined with arthroscopic microfracture. Recorded were the patients' visual analogue scale (VAS) pain scores and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores at 6 months and 12 months after surgery, levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor- α (TNF- α) at 1 month after surgery, lesion area at 12 months after surgery, and incidence of complications. Results:The follow-up time for this cohort was (16.2±6.7) months. The AOFAS score was (61.52±6.75) points before surgery, (84.15±5.56) points at 6 months after surgery and (95.67±4.30) points at 12 months after surgery. The VAS score was (5.88±1.02) points before surgery, (2.12±0.48) points at 6 months after surgery and (0.66±0.36) points at 12 months after surgery. The two-by-two comparisons between the 3 time points for the above items were statistically significant ( P<0.05). IL-1 was (32.37±6.64) pg/mL, IL-6 (34.04±7.12) pg/mL, and TNF- α (17.89±4.96) ng/L at 1 month after surgery in the 27 patients, all of which were significantly lower than their preoperative levels [(96.63±14.80) pg/mL, (102.33±20.42) pg/mL, and (54.48±9.33) ng/L] ( P<0.05). The lesion area was (28.66±6.52) mm 2 at 12 months after surgery, significantly smaller than the value before surgery [(128.52±11.32) mm 2] ( P<0.05). Infection at the adjustable external fixation needle track occurred in 1 patient and lower limb thrombosis in 2 patients. Conclusion:In the treatment of OLT, adjustable external fixation and traction combined with arthroscopic microfracture can achieve satisfactory results and improve symptoms for the patients.

The value of the modified 5-factor frailty index in assessing postoperative complications and mortality in elderly patients with hip fractures / 中华老年医学杂志

Objective:To analyze the value of the modified 5-factor frailty index in assessing postoperative complications and mortality in elderly hip fracture patients.Methods:In this retrospective study, clinical data were collected of hip fracture patients aged 60 years and above surgically treated at Beijing Luhe Hospital affiliated to Capital Medical University between January 2015 and December 2019.Patients' group assignment was based on whether the modified frailty index score was ≤1 or ≥2, and a post-surgery follow-up was conducted for survival at 30 days, 1 year, 2 years, and 4 years, which was analyzed by the Kaplan-Meier method.Multivariate Cox regression analysis was used to identify factors affecting death in elderly patients.Results:A total of 1 208 patients were included, with 890 in the group with the index score ≤1 and 318 in the group with the index score ≥2.There was no difference in mortality at 30 days(1.6% or 14/890 vs.1.9% or 6/318, P=0.707), 1-year(11.3% or 99/874 vs.11.6% or 36/310, P=0.917), 2-years(19.7% or 168/852 vs.24.3% or 73/300, P=0.099)and 4-years(44.0% or 238/541 vs.51.5% or 106/206, P=0.071). The incidence of postoperative complications in the group with the score ≥2 was higher(14.8% or 47/318 vs.9.7% or 86/890, P=0.012), including the incidence of stroke(6.3% or 20/318 vs.1.8% or 16/890, P<0.001)and the incidence of postoperative pneumonia(6.0% or 19/318 vs.3.1% or 28/890, P=0.029), and the differences were statistically significant.Multivariate Cox regression analysis showed that age, being female, the Charlson comorbidity index score and low hemoglobin at admission were risk factors for 1-year, 2-year and 4-year mortality post-surgery(all P<0.05), while the modified frailty index score had no correlation with postoperative mortality. Conclusions:A modified frailty index ≥2 is predictive of increased risk of postoperative pneumonia and stroke in patients with hip fractures, but is not correlated with the risk of postoperative mortality.

Discussion on Disease Mechanism， Pattern Differentiation， and Treatment of Autoimmune Diseases Based on the Theory of "Transformation of Healthy Qi into Pathogenic Qi" / 中医杂志

Based on the duality of "healthy" and "pathogenic" of the immune system in physiological and pathological states， and combined with the analogy between "immune function" and "healthy qi"， the theory of "transformation of healthy qi into pathogenic qi" was proposed to guide the pattern identification and treatment of autoimmune diseases. The theory of "transformation of healthy qi into pathogenic qi" means that "healthy qi"， which is originally used by the body's original ability to defend and remove harmful factors or normal functional activities， transformed into "pathogenic qi"， which is factors that damage and destroy the human body or abnormal body state. In the pathogenesis of autoimmune diseases， the pathogenic factors and causes of congenital endowment， tissue damage under the influence of external pathogens， abnormal function of zang-fu （脏腑） organs and meridians， abnormal transmission and transformation of qi， blood， body fluids was proposed. Autoimmune diseases have the dynamic mechanism of latent pathogen at early stage， internal and external contraction at the onset stage， and the expansion of the pathogenic qi at the complete period， and also have the characteristics of the specificity， invisibility and contradiction of healthy qi and pathogenic qi. In terms of treatment， it advocates the ideas of treatment with both attack and supplementation throughout the disease， identifying diseases with special prescriptions and formulas for specific diseases， dynamically adjusting treatment by identifying the remission and onsets of the disease， observing the changes in the dynamics of healthy qi transforming into pathogenic qi， and treating disease before it arises with early intervention.

Research advances in exosomal proteins,mRNA and non-coding RNA regulation of Hepatocellular Carci-noma / 实用医学杂志

Exosomes are extracellular vesicles commonly detected in numerous body fluids and contain a variety of components such as proteins,nucleic acids,lipids,and metabolites.These components enable exosomes to mediate intercellular communication and impact diverse cellular processes.Recently,research has highlighted that exosomes have a significant regulatory role in numerous aspects of hepatocellular carcinoma(HCC)occur-rence,development,and drug resistance.Non-coding RANs,a crucial component of exosomes,can regulate the HCC tumour microenvironment with a direct impact on biological behaviours such as tumour growth,metastasis,angiogenesis,and immunomodulation.To this end,exosomes present an interesting avenue for further research in the field of HCC therapy.It is anticipated to become a novel diagnostic,prognostic marker,or therapeutic target for hepatocellular carcinoma(HCC).Our review of the role played by exosomal components in HCC progression over the last five years aims to furnish references and innovative perspectives for early diagnosis,prognosis,and treatment of HCC.

Nanomaterial-based Therapeutics for Biofilm-generated Bacterial Infections / 生物化学与生物物理进展

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.

Functional effects of microRNA-211-5p-targeted inhibition of erythropoietin hepatocyte kinase receptor and ligand B2 signaling pathway on spinal cord nerve injury / 中国医师进修杂志

Objective:To detect the expression of microRNA (miR)-211-5p, erythropoietin hepatocyte kinase receptor B2 (EphB2) and erythropoietin hepatocyte kinase ligand B2 (ephrin B2) in spinal cord tissues as well as nerve cells after spinal cord injury (SCI), and to explore their mechanisms and effects on neurological recovery in SCI rats.Methods:The study was conducted from May 2020 to June 2021 using Sprague Dawley (SD) rats and PC12 cells. SD rats were divided into sham-operated group and SCI group of 30 rats each, and Basso-Beattie-Bresnahan (BBB) score were performed at different postoperative time points (1, 3, 7, 14, 21 and 28 d), and the relative expression of miR-211-5p and Eph/ephrin B2 mRNA was measured by quantitative real-time polymerase chain reaction (qPCR); the SCI rats were divided into recombinant lentiviral vector LV-miR-211-5p group (group A), empty lentiviral vector LV-eGFP (group B) and saline group (group C), with 15 rats in each group, respectively. The recombinant lentiviral vector, empty lentiviral vector and saline were injected on the cephalic and caudal sides of the spinal cord injury, and the relative expression of miR-211-5p and Eph/ephrin B2 mRNA in the spinal cord tissue was measured at 1, 7 and 14 d after surgery. In addition, a PC12 injury cell line model was established with 150 μmol/L hydrogen peroxide (H 2O 2), and the apoptosis rate and apoptosis-related proteins and contents of different cell lines were detected by flow cytometry and Western blot, respectively. MiR-211-5p was verified to target EphB2 by dual luciferase reporter gene. Results:The results of the animal experiments showed that at different postoperative time points, the miR-211-5p levels in the SCI group were lower than those in the SHAM group: 0.70 ± 0.03 vs. 1.00 ± 0.10, 0.60 ± 0.04 vs. 1.00 ± 0.05, 0.45 ± 0.10 vs. 1.00 ± 0.12, 0.30 ± 0.06 vs. 1.00 ± 0.15, 0.20 ± 0.05 vs. 1.00 ± 0.13, 0.10 ± 0.02 vs. 1.00 ± 0.07. In contrast, levels of Eph/ephrin B2 were higher in the SCI group compared to the SHAM group: 1.10 ± 0.05 vs. 1.00 ± 0.01, 1.80 ± 0.01 vs. 1.00 ± 0.08, 2.30 ± 0.01 vs. 1.00 ± 0.10, 2.60 ± 0.01 vs. 1.00 ± 0.05, 2.80 ± 0.01 vs. 1.00 ± 0.06, 3.00 ± 0.01 vs. 1.00 ± 0.07 and 1.20 ± 0.05 vs. 1.00 ± 0.02, 1.60 ± 0.01 vs. 1.00 ± 0.03, 2.10 ± 0.10 vs. 1.00 ± 0.01, 2.40 ± 0.11 vs. 1.00 ± 0.09, 2.70 ± 0.13 vs. 1.00 ± 0.05, 2.90 ± 0.12 vs. 1.00 ± 0.03 ( P<0.05). At 14 d after surgery, Group A exhibited higher BBB scores than Groups B and C: (14.0 ± 1.1) points vs. (8.0 ± 1.1) and (8.2 ± 1.2) points, while miR-211-5p levels were higher than those in Groups B and C: 1.90 ± 0.10 vs. 0.40 ± 0.01 and 0.50 ± 0.02, and Eph/ephrin B2 levels were lower than those in Groups B and C: 0.70 ± 0.10 vs. 1.80 ± 0.04 and 1.90 ± 0.06, 0.60 ± 0.03 vs. 2.00 ± 0.04 and 2.10 ± 0.05 ( P<0.05). Immunofluorescence staining showed that the levels of GAP-43 and synaptophysin in group A were higher than those in groups B and C at 14 d after surgery ( P<0.05). Cellular assays showed that overexpression of miR-211-5p inhibited the apoptosis rate of H 2O 2-induced PC12 cells and the expression of the apoptosis-related gene Cleaved-caspase3 ( P<0.05). Knockdown of miR-211-5p increased the apoptosis rate of H 2O 2-induced PC12 cells and the expression of the apoptosis-related gene Cleaved-caspase3 ( P<0.05). Dual luciferase reporter gene assay confirmed that EphB2 was a target gene of miR-211-5p and overexpression of EphB2 antagonized the inhibitory apoptosis effect of miR-211-5p on H 2O 2-induced PC12 cells. Conclusions:This study showed that miR-211-5p could promote neurological repair in SCI by inhibiting the expression of Eph/ephrin B2 signaling pathway, suggesting that using miR-211-5p as a target to inhibit Eph/ephrin B2 signaling pathway may have a protective effect on SCI.

Application of the excellent doctor-oriented teaching evaluation method in the clinical teaching of dermatology and venereology / 中华医学教育探索杂志

Objective:To investigate the application value of the teaching evaluation method guided by cultivating "excellent doctors" in the clinical teaching of dermatology and venereology.Methods:A non-simultaneous control study was conducted, and the medical students who received theoretical learning and clinical internship in Department of Dermatology and Venereology, Affiliated Hospital of North Sichuan Medical College, from March 2020 to February 2022, were enrolled as subjects. According to the order of enrollment, 32 students who were enrolled from March 2020 to February 2021 were set up as control group, and 31 students who were enrolled from March 2021 to February 2022 were set up as experimental group. The students in the control group received lecture-based learning, and those in the experimental group received clinical teaching using a teaching and evaluation method guided by cultivating "excellent doctors". After the course ended, the two groups were compared in terms of the scores of theoretical knowledge and operation skills, clinical thinking ability [Self-Assessment of Clinical Reasoning and Reflection (SACRR)], core competence [Mini-Clinical Evaluation Exercise (Mini CEX)], and degree of satisfaction with teaching. SPSS 25.0 software was used to perform the independent samples t-test, the Mann-Whitney U test, the chi-square test, and the rank sum test. Results:One student in the control group voluntarily withdrew from the study, and one student in the experimental group did not complete the contents of internship. Finally, 31 students in the control group and 30 in the experimental group were included in the study. After 4 weeks of internship, compared with the control group, the experimental group had significantly higher scores of theoretical knowledge (88.00±4.30 vs. 85.71±4.12, t=2.12, P=0.040) and operation skills (91.87±3.99 vs. 88.23±3.84, t=3.63, P<0.05). After 4 weeks of internship, compared with the control group, the experimental group had significantly higher information systematization score (47.23±3.11 vs. 45.16±3.00), analysis problem score (34.87±2.30 vs. 31.29±2.30), truth finding score (16.30±1.49 vs. 14.45±1.52), reflective ability score [3.50 (3.00, 4.00) vs. 3.00 (3.00, 3.00)], and total score of SACRR (101.87±4.47 vs. 93.90±4.47), with significant differences between the two groups ( t/ Z=2.65, 6.17, 4.79, 3.15, and 6.96, all P<0.05). After 4 weeks of internship, the experimental group had a significantly better core competence than the control group ( Z=2.12, P=0.030); compared with the control group, the experimental group had significantly higher classroom teaching score (20.17±1.98 vs. 18.45±2.23, t=3.17, P<0.05), clinical practice score (19.83±2.10 vs. 17.65±2.17, t=4.00, P<0.05), learning plan score (18.63±2.24 vs. 17.03±2.15, t=2.85, P<0.05), teaching resource score (20.07±1.82 vs. 18.58±2.00, t=3.04, P<0.05) and total score (78.70±3.67 vs. 71.71±4.13, t=6.98, P<0.05). Conclusions:The application of the teaching and evaluation method guided by cultivating "excellent doctors" in the clinical teaching of dermatology and venereology can improve clinical theoretical knowledge, practical operation skills, clinical thinking ability, and core ability among interns and thus help to improve teaching quality. Therefore, it holds promise for clinical application.

Melatonin Attenuates Mitochondrial Damage in Aristolochic AcidInduced Acute Kidney Injury

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Construction of a Prognostic Model of Multiple Myeloma Based on Metabolism-Related Genes / 中国实验血液学杂志

OBJECTIVE@#To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes.@*METHODS@#The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score.@*RESULTS@#A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (P<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (P<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect.@*CONCLUSION@#Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.

Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice

Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of Panax ginseng C. A. Meyer, Lilium brownie F. E. Brown ex Miellez var. viridulum Baker, Polygonatum sibiricum Delar. ex Redoute, Lonicera japonica Thunb., Hippophae rhamnoides Linn., Amygdalus Communis Vas, Platycodon grandiflorus (Jacq.) A. DC., and Cortex Phelloderdri. Herein, we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota. BWBDS protected mice against SILI, which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity. BWBDS selectively promoted the growth of Lactobacillus johnsonii (L. johnsonii) in cecal ligation and puncture treated mice. Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, L. johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing interleukin-10+ M2 macrophage production and enhancing intestinal integrity. Furthermore, heat inactivation L. johnsonii (HI-L. johnsonii) treatment promoted macrophage anti-inflammatory activity and alleviated SILI. Our findings revealed BWBDS and gut microbiota L. johnsonii as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, via L. johnsonii-dependent immune regulation and interleukin-10+ M2 macrophage production.

Low diastolic blood pressure and adverse outcomes in inpatients with acute exacerbation of chronic obstructive pulmonary disease: A multicenter cohort study / 中华医学杂志(英文版)

BACKGROUND@#Although intensively studied in patients with cardiovascular diseases (CVDs), the prognostic value of diastolic blood pressure (DBP) has little been elucidated in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study aimed to reveal the prognostic value of DBP in AECOPD patients.@*METHODS@#Inpatients with AECOPD were prospectively enrolled from 10 medical centers in China between September 2017 and July 2021. DBP was measured on admission. The primary outcome was all-cause in-hospital mortality; invasive mechanical ventilation and intensive care unit (ICU) admission were secondary outcomes. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regressions were used to identify independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes.@*RESULTS@#Among 13,633 included patients with AECOPD, 197 (1.45%) died during their hospital stay. Multivariable Cox regression analysis showed that low DBP on admission (<70 mmHg) was associated with increased risk of in-hospital mortality (HR = 2.16, 95% CI: 1.53-3.05, Z = 4.37, P <0.01), invasive mechanical ventilation (HR = 1.65, 95% CI: 1.32-2.05, Z = 19.67, P <0.01), and ICU admission (HR = 1.45, 95% CI: 1.24-1.69, Z = 22.08, P <0.01) in the overall cohort. Similar findings were observed in subgroups with or without CVDs, except for invasive mechanical ventilation in the subgroup with CVDs. When DBP was further categorized in 5-mmHg increments from <50 mmHg to ≥100 mmHg, and 75 to <80 mmHg was taken as reference, HRs for in-hospital mortality increased almost linearly with decreased DBP in the overall cohort and subgroups of patients with CVDs; higher DBP was not associated with the risk of in-hospital mortality.@*CONCLUSION@#Low on-admission DBP, particularly <70 mmHg, was associated with an increased risk of adverse outcomes among inpatients with AECOPD, with or without CVDs, which may serve as a convenient predictor of poor prognosis in these patients.@*CLINICAL TRIAL REGISTRATION@#Chinese Clinical Trail Registry, No. ChiCTR2100044625.

Clinical application of Chaihu Jia Longgu Muli Decoction based on modern pathophysiology mechanism / 中国中药杂志

Chaihu Jia Longgu Muli Decoction was firstly recorded in Treatise on Cold Damage(ZHANG Zhong-jing, Eastern Han dynasty). According to this medical classic, it is originally used in the treatment of the Shaoyang and Yangming syndrome. Based on the modern pathophysiological mechanism, this study interpreted the classic provisions of Chaihu Jia Longgu Muli Decoction. Original records of "chest fullness" "annoyance" "shock" "difficult urination" "delirium" "heavy body and failing to turn over" all have profound pathophysiological basis, involving disorders in cardiovascular, respiratory, nervous, and mental systems. This formula is widely used, which can be applied to treat epilepsy, cerebral arteriosclerosis, cerebral infarction, and other cerebrovascular diseases, hypertension, arrhythmia, and other cardiovascular diseases, insomnia, constipation, anxiety, depression, cardiac neurosis and other acute and chronic diseases as well as diseases in psychosomatic medicine. The clinical indications include Bupleuri Radix-targeted syndrome such as fullness and discomfort in chest and hypochondrium, bitter taste mouth, dry throat, and dizziness, the insomnia, anxiety, depression, susceptibility to fright, upset, dreamfulness and other psychiatric symptoms, red tongue, thick and yellow tongue coating, and wiry hard and powerful pulse. This formula was found to be used in combination with other formulas, such as Gualou Xiebai Decoction, Wendan Decoction, Zhizhu Pills, Juzhijiang Decoction, Suanzaoren Decoction, and Banxia Baizhu Tianma Decoction.

Application of folded transverse superficial epigastric artery perforator flap for large penetrating defect after buccal carcinoma resection / 中国修复重建外科杂志

OBJECTIVE@#To explore the effectiveness of folded transverse superficial epigastric artery perforator flap in repairing the large penetrating defect after buccal carcinoma resection.@*METHODS@#Between January 2019 and June 2021, 12 patients with buccal squamous cell carcinoma were treated. There were 6 males and 6 females with an average of 66.9 years (range, 53-79 years). The pathological stage was T3a-T4b, and the preoperative mouth opening was (3.08±0.46) cm. The disease duration ranged from 6 to 24 months, with an average of 15 months. After buccal carcinoma radical resection and neck lymph node dissection, the penetrating defects in size of 8 cm×6 cm to 16 cm×8 cm and in depth of 0.5-1.5 cm were remained. The transverse superficial epigastric artery perforator flap in size of 8 cm×6 cm to 14 cm×8 cm were harvested and folded to repair the penetrating defects. The donor site was sutured directly.@*RESULTS@#All 12 skin flaps survived after operation, and the wounds healed by first intention. No internal or external fistula complications occurred. All incisions at the recipient site healed by first intention. All patients were followed up 12-18 months (mean, 14 months). There was no obvious abnormality in the color and texture of the flap, the oral and facial appearances were symmetrical, and there was no obvious swelling in the cheek. At last follow-up, the patient's mouth opening was (2.89±0.33) cm, which was not significantly different from that before operation ( t=1.879, P=0.087). The subjective satisfaction scores of 12 patients were 6-8 points, with an average of 7.3 points. Significant scars remained at the donor site but concealed in location.@*CONCLUSION@#The folded transverse superficial epigastric artery perforator flap can be used as a surgical method for repairing large penetrating defects after the buccal carcinoma resection, with a good recovery of facial appearance and oral function.

Effectiveness and risk factors of supramalleolar osteotomy in treatment of varus-type ankle arthritis / 中国修复重建外科杂志

OBJECTIVE@#To assess the effectiveness of supramalleolar osteotomy (SMOT) as a therapeutic intervention for varus-type ankle arthritis, while also examining the associated risk factors that may contribute to treatment failure.@*METHODS@#The clinical data of 82 patients (89 feet) diagnosed with varus-type ankle arthritis and treated with SMOT between January 2016 and December 2020 were retrospectively analyzed. The patient cohort consisted of 34 males with 38 feet and 48 females with 51 feet, with the mean age of 54.3 years (range, 43-72 years). The average body mass index was 24.43 kg/m 2 (range, 20.43-30.15 kg/m 2). The preoperative tibial anterior surface angle (TAS) ranged from 77.6° to 88.4°, with a mean of 84.4°. The modified Takakura stage was used to classify the severity of the condition, with 9 feet in stage Ⅱ, 41 feet in stage Ⅲa, and 39 feet in stage Ⅲb. Clinical functional assessment was conducted using the Maryland sore, visual analogue scale (VAS) score, and psychological and physical scores in Health Survey 12-item Short From (SF-12). Radiology evaluations include TAS, talar tilt (TT), tibiocrural angle (TC), tibial medial malleolars (TMM), tibiocrural distance (TCD), tibial lateral surface angle (TLS), and hindfoot alignment angle (HAA). The results of clinical failure, functional failure, and radiology failure were statistically analyzed, and the related risk factors were analyzed.@*RESULTS@#The operation time ranged from 45 to 88 minutes, with an average of 62.2 minutes. No complication such as fractures and neurovascular injuries was found during operation. There were 7 feet of poor healing of the medial incision; 9 pin tract infections occurred in 6 feet using external fixator; there were 20 cases of allograft and 3 cases of autograft with radiographic bone resorption. Except for 1 foot of severe infection treated with bone cement, the remaining 88 feet were primary healing, and the healing area was more than 80%. All patients were followed up 24-82 months, with an average of 50.2 months. Maryland score, VAS score, SF-12 psychological and physiological scores, and TAS, TC, TLS, TCD, TT, TMM, HAA, and Takakura stage were significantly improved at last follow-up ( P<0.05). Postoperative clinical failure occurred in 13 feet, functional failure in 15 feet, and radiology failure in 23 feet. Univariate analysis showed that obesity, TT>10°, and Takakura stage Ⅲb were risk factors for clinical failure, HAA≥15° and Takakura stage Ⅲb were risk factors for functional failure, and TT>10° was risk factor for radiographic failure ( P<0.05). Further logistic regression analysis showed that TT>10°, HAA≥15°, and TT>10° were risk factors for clinical failure, functional failure, and radiographic failure, respectively ( P<0.05).@*CONCLUSION@#SMOT is effective in the mid- and long-term in the treatment of varus-type ankle arthritis, but it should be used with caution in patients with obesity, severe hindfoot varus, severe talus tilt, and preoperative Takakura stage Ⅲb.

Comparison of efficacy of platelet-rich plasma and extracorporeal shock wave for the treatment of chronic insertional Achilles tendinopathy / 中国骨伤

OBJECTIVE@#To compare clinical efficacy of platelet-rich plasma (PRP) and extracorporeal shock wave in treating chronic insertional Achilles tendinopathy.@*METHODS@#From February 2019 to August 2021, 42 patients with chronic insertional Achilles tendinopathy were selected and divided into PRP group(20 patients, 28 feet) and shock wave group (22 patients, 29 feet). In PRP group, there were 12 males and 8 females, aged 47.00(28.00, 50.75) years old, and the courses of disease ranged 7.00(6.00, 7.00) months;PRP injection was performed in the Achilles tendon stop area of the affected side. In shock wave group, there were 16 males and 6 females, aged 42.00(35.75, 47.25) years old;and the courses of disease was 7.00(6.00, 8.00) months;shock wave was performed in Achilles tendon stop area of the affected side and triceps surae area. Visual analogue scale (VAS) and Victorian Institute of Sport Assessment-Achilles (VISA-A) were applied to evaluate clnical effect before treatment, 1, 3 and 6 months after treatment, and satisfaction of patients was investigated.@*RESULTS@#VAS and VISA-A score in both groups were significantly improved at 1, 3 and 6 months after treatment than before treatment (P<0.05), VAS and VISA-A score in PRP group at 6 months after treatment were significantly higher than those at 1 and 3 months after treatment, and VAS and VISA-A score in shock wave group were lower than those at 1 and 3 months after treatment (P<0.05). There was no significant difference in VAS and VISA-A score between two groups before treatment, 1 and 3 months after treatment(P>0.05), while VAS and VISA-A score in PRP group were better than those in shock wave group at 6 months after treatment(P<0.05), and the satisfaction survey in PRP group was better than that in shock wave group(P<0.05).@*CONCLUSION@#PRP injection has a good clinical effect on chronic insertional Achilles tendinopathy with high patient satisfaction, and medium-and long-term effect of PRP injection for the treatment of chronic insertional Achilles tendinopathy is better than that of extracorporeal divergent shock wave.

Isolation of Leclercia adecarboxylata Producing Carbapenemases in A Newborn Female / 生物医学与环境科学（英文）

Leclercia adecarboxylata is a Gram-negative bacterium belonging to the Enterobacteriaceae family. To our knowledge, this is the first report of a carbapenem-resistant L. adecarboxylata strain isolated from a healthy newborn. The L. adecarboxylata strain isolated in this study carried four plasmids that may serve as reservoirs for antibiotic resistance genes. Plasmids 2 and 4 did not harbor any antimicrobial resistance genes. Plasmid 3 is a novel plasmid containing three resistance genes. The bla IMP gene harbored in the strain was most similar to bla IMP-79 at the nucleotide level, with a similarity of 99.4% (737/741). This case highlights the importance of considering L. adecarboxylata as a potential cause of infections in children.

Safety and efficacy of transcatheter closure of Fontan fenestration with atrial septal occluder / 中华心血管病杂志

Objective: To assess the safety and efficacy of transcatheter fenestration closure following Fontan procedure with an atrial septal occluder. Methods: This is a retrospective study. The study sample consists of all consecutive patients who underwent closure of a fenestrated Fontan baffle at Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine between June 2002 and December 2019. The indications of Fontan fenestration closure included that normal ventricular function, targeted drugs for pulmonary hypertension and positive inotropic drugs were not required prior the procedure; and the Fontan circuit pressure was less than 16 mmHg (1 mmHg=0.133 kPa) and no more than a 2 mmHg increase during test occlusion of the fenestration. Electrocardiogram and echocardiography were reviewed at 24 hours, 1, 3, 6 months and annually thereafter post procedure. Follow-up information including clinical events and complications related to Fontan procedure was recorded. Results: A total of 11 patients, including 6 males and 5 females, aged (8.9±3.7) years old were included. The types of Fontan were extracardiac conduits (7 cases) and intra-atrial duct (4 cases). The interval between percutaneous fenestration closure and the Fontan procedure was (5.1±2.9) years. One patient reported recurrent headache after Fontan procedure. Successful fenestration occlusion with atrial septal occluder was achieved in all patients. Compared with prior closure, Fontan circuit pressure ((12.72±1.90) mmHg vs. (12.36±1.63) mmHg, P<0.05), and aortic oxygen saturation ((95.11±3.11)% vs. (86.35±7.26)%, P<0.01) were increased. There were no procedural complications. At a median follow-up of (3.8±1.2) years, there was no residual leak and evidence of stenosis within the Fontan circuit in all patient. No complication was observed during follow-up. One patient with preoperative headache did not have recurrent headache after closure. Conclusions: If the Fontan pressure is acceptable by test occlusion during the catheterization procedure, Fontan fenestration could be occluded with the atrial septum defect device. It is a safe and effective procedure, and could be used for occlusion of Fontan fenestration with varying sizes and morphologies.

Bioinformatics analysis and key gene verification of sepsis myocardial macrophage microarray data based on GEO database / 中华心血管病杂志

Objective: Bioinformatics analysis was used to screen differentially expressed genes (DEGs) in macrophages of sepsis myocardial injury and to verify key genes. Methods: Experiment 1 (gene chip and bioinformatics analysis): The gene chip data GSE104342 of cardiac macrophages in septic mice was downloaded from Gene Expression Omnibus database. DEGs were obtained by R language analysis. DAVID online database was used to obtain gene ontology and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs. STRING online database was used for protein-protein interaction network analysis of DEGs, and then key genes were screened by using Cytoscape software and molecular complex detection (MCODE) plug-ins. Experiment 2 (sepsis model construction and related protein verification): Ten male C57BL/6 mice, aged 8-14 weeks. Five mice were randomly selected as control group, and 5 mice were selected as the sepsis group by building a mice sepsis model in vivo. Echocardiography was used to detect the cardiac function. Hematoxylin-eosin staining was used to assess the cardiac morphology. TUNEL staining was used to evaluate cardiomyocyte apoptosis. Immunofluorescence staining was used to detect the expression of differentiation antigen cluster 206 (CD206),inducible nitric oxide synthases (iNOS),F4/80,suppressor of cytokine signaling 3 (Socs3) ,interleukin 1 receptor antagonist (Il1rn) and chemokine C-C motif ligand 7 (Ccl7) protein. RAW264.7 macrophages were cultured in vitro and divided into 2 groups: LPS groupstimulated by lipopolysaccharide (LPS, 1 mg/L) and blank control group treated with equal-volume phosphate buffer solution. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of Socs3, Il1rn and Ccl7 in vitro. Results: Experiment 1: 24 647 genes were screened in GSE104342 dataset and 177 genes (0.72%) were differential expression, including 120 up-regulated genes and 57 down-regulated genes. Gene ontology enrichment analysis showed that DEGs were mainly involved in inflammatory response, immune response, apoptosis regulation and antigen processing and presentation. KEGG signaling pathway analysis showed that DEGs in cardiac macrophages of septic mice were mainly enriched in cytokine-cytokine receptor interaction, tumor necrosis factor signaling pathway, NOD like receptor signaling pathway. Three hub genes were obtained by STRING and Cytoscape analysis, including Socs3, Il1rn and Ccl7. Experiment 2: In vivo, it was found that compared with the control group, the cardiac function of the sepsis mice decreased significantly, the myocardial cells were significantly edema, inflammatory cell infiltration, myocardial fiber rupture, some myocardial nuclei dissolved and disappeared, and the cardiomyocyte apoptosis increased, suggesting that the sepsis myocardial injury model of mice was successfully constructed. Compared with the control group, the expression of CD206 in the myocardium of septic mice was down-regulated, the expression of iNOS, F4/80, Socs3, Il1rn and Ccl7 were up-regulated. In addition, there was co-localization between Socs3, Il1rn, Ccl7 and F4/80 protein. Compared with the blank control group, the expression of Socs3, Il1rn and Ccl7 significantly upregulated after LPS intervention in vitro by RT-PCR. Conclusions: The selected key genes Socs3, Il1rn and Ccl7 were up-regulated in myocardial macrophages of septic mice. Socs3, Il1rn and Ccl7 are expected to become new targets for the diagnosis and treatment of sepsis cardiac injury.

Traditional Chinese therapy in the treatment of ICU-acquired weakness: a Meta-analysis / 中华危重病急救医学

OBJECTIVE@#To systematically assess the efficacy of traditional Chinese therapy in the treatment of ICU-acquired weakness (ICU-AW).@*METHODS@#PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP were retrieved by computer and were used to collect a randomized controlled trials (RCT) of traditional Chinese therapy for ICU-AW. The retrieval time was from databases establishment to December 2021. After 2 researchers independently screened the literature, extracted data and evaluated the risk of bias included in the study, and RevMan 5.4 software was used for Meta-analysis.@*RESULTS@#334 articles were selected, totally 13 clinical studies and 982 patients were included, including 562 in the trial group and 420 in the control group. Meta-analysis results showed that traditional Chinese therapy could improve clinical efficacy of ICU-AW patients [relative risk (RR) = 1.35, 95% confidence interval (95%CI) was 1.20 to 1.52, P < 0.000 01], improve the muscle strength [Medical Research Council score (MRC score); standardized mean difference (SMD) = 1.00, 95%CI was 0.67 to 1.33, P < 0.000 01], improve daily life ability [modified Barthel index score (MBI score); SMD = 1.67, 95%CI was 1.20 to 2.14, P < 0.000 01], shorten mechanical ventilation time (SMD = -1.47, 95%CI was -1.84 to -1.09, P < 0.000 01), reduce the length of intensive care unit (ICU) stay [mean difference (MD) = -3.28, 95%CI was -3.89 to -2.68, P < 0.000 01], reduce the total hospitalization time (MD = -4.71, 95%CI was -5.90 to -3.53, P < 0.000 01), reduce tumor necrosis factor-α (TNF-α; MD = -4.55, 95%CI was -6.39 to -2.70, P < 0.000 01) and interleukin-6 (IL-6; MD = -5.07, 95%CI was -6.36 to -3.77, P < 0.000 01). There was no obvious advantage in reducing the severity of the disease [acute physiology and chronic health evaluation II (APACHE II; SMD = -0.45, 95%CI was -0.92 to 0.03, P = 0.07).@*CONCLUSIONS@#Based on the current research, traditional Chinese therapy can improve the clinical efficacy of ICU-AW, improve muscle strength and daily life ability, shorten mechanical ventilation, the length of ICU stay and total hospitalization time, reduce TNF-α and IL-6. But traditional Chinese therapy can not reduce the overall disease severity.