The biofilm is a major pathogenic factor for many types of chronic infections,and Escherichia coli bio-film plays an important role in community-acquired infection and hospital-acquired infection and is one of common causes of urinary tract infection(UTI).The quorum sensing(QS)system of E.coli biofilm can mediate intercel-lular information exchange and thus regulate the whole community to adapt to the environmental changes,and the extracellular matrix-derived complex resistance mechanisms lead to a certain degree of bacterial resistance to anti-microbial drugs and resistance to immune system,which then makes it difficult for the conventional antimicrobial drugs to effectively eradicate the biofilm-associated infections.The article focuses on the formation of E.coli bio-film,drug resistance mechanisms and treatment aspects and summarizes the progress of research on the novel substitutive therapies against the E.coli biofilms that were developed in recent years,such as phytochemicals,nanomaterials,probiotics and phage therapy,so as to provide theoretical bases for the clinical treatment and the development of novel drug therapies against the E.coli biofilm.

The biofilm is a major pathogenic factor for many types of chronic infections,and Escherichia coli bio-film plays an important role in community-acquired infection and hospital-acquired infection and is one of common causes of urinary tract infection(UTI).The quorum sensing(QS)system of E.coli biofilm can mediate intercel-lular information exchange and thus regulate the whole community to adapt to the environmental changes,and the extracellular matrix-derived complex resistance mechanisms lead to a certain degree of bacterial resistance to anti-microbial drugs and resistance to immune system,which then makes it difficult for the conventional antimicrobial drugs to effectively eradicate the biofilm-associated infections.The article focuses on the formation of E.coli bio-film,drug resistance mechanisms and treatment aspects and summarizes the progress of research on the novel substitutive therapies against the E.coli biofilms that were developed in recent years,such as phytochemicals,nanomaterials,probiotics and phage therapy,so as to provide theoretical bases for the clinical treatment and the development of novel drug therapies against the E.coli biofilm.

Objective: To investigate the mechanism by which serum amyloid P component (SAP) alleviates periodontitis in mice, providing an experimental basis to establish SAP as a novel therapeutic agent for periodontitis. Methods: Ethical approval was obtained from the Institutional Animal Ethics Committee. Periodontitis models were established in wild-type (WT) mice and SAP-transgenic (SAP-Tg) mice, divided into four groups: WT control (WT group), WT periodontitis (WT+P group), SAP-Tg control (Tg group), and SAP-Tg periodontitis (Tg+P group). On day 7, the mice were euthanized, and periodontal tissues, teeth, and alveolar bone were collected. SAP protein expression was detected by enzyme-linked immunosorbent assay (ELISA). Micro-CT and HE staining were used to measure alveolar bone resorption (distance from the cementoenamel junction to the alveolar bone crest). Tartrate-resistant acid phosphatase (TRAP) staining was performed to assess osteoclast number, and immunohistochemistry (IHC) was employed to evaluate macrophage infiltration. The expression levels of inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by qRT-PCR. Oral microorganism composition was analyzed using 16S ribosomal RNA (16S rRNA) gene sequencing. Additionally, macrophages from WT and SAP-Tg mice were isolated to establish an in vitro inflammation model, divided into WT+LPS and Tg+LPS groups. The expression of macrophage polarization-related genes including inducible nitric oxide synthase (iNOS), CD86, CD163, and CD206) were assessed by qRT-PCR. After the induction of osteoclast differentiation, TRAP staining was performed. Results: ELISA results demonstrated that periodontal tissues from Tg+P group mice exhibited higher levels of SAP expression compared to the WT+P group. Micro-CT and HE staining analyses revealed that the Tg+P group showed reduced alveolar bone resorption, indicated by a shorter distance between the cementoenamel junction and alveolar bone crest, compared to the WT+P group. Furthermore, TRAP staining results indicated a decrease in osteoclast numbers in the Tg+P group compared to the WT+P group. IHC and qRT-PCR results indicated reduced macrophage infiltration and decreased expression of IL-1β, IL-6, and TNF-α in the Tg+P group. Oral microorganism sequencing showed no significant difference in periodontitis-associated pathogenic bacteria between WT+P and Tg+P groups. In vitro experiments demonstrated that compared to the WT+LPS group, the Tg+LPS group exhibited downregulated M1 macrophage markers (iNOS and CD86) and upregulated M2 macrophage markers (CD163 and CD206). TRAP staining confirmed fewer osteoclasts in the Tg+LPS group. Conclusion SAP overexpression effectively alleviates periodontitis severity in mice by inhibiting M1 macrophage polarization, reducing pro-inflammatory cytokine expression, and suppressing osteoclast differentiation, thereby attenuating alveolar bone resorption.

Objective To investigate the protective effect of exogenous leptin against focal cerebral ischemia-reperfusion(I/R)injury in mice and explore the underlying mechanism.Methods A total of 100 C57BL/6 mice were randomly divided into 5 groups,including a sham-operated group,cerebral I/R model group,and 3 leptin treatment groups with intraperitoneal injections of 0.5,1.0 or 2.0 leptin immediately after occlusion of the internal carotid artery.At 24 h after reperfusion,neurological function scores of the mice were assessed,and TTC staining was used to determine the area of cerebral infarction.The pathological changes in the cortical brain tissue of the mice were observed using HE staining,and degenerative damage of the cortical neurons were assessed with Fluoro-Jade C staining.The expression of glial fibrillary acidic protein in cortical brain tissues was detected using immunohistochemistry and Western blotting.In another 45 C57BL/6 mice with sham operation,I/R modeling,or leptin(1 mg/kg)treatment,glutamic acid in the cortical brain tissue was detected using glutamate assay,and cortical glutamate-aspartate transporter(GLAST)and glutamate transporter-1(GLT-1)protein expressions were detected using immunohistochemistry.Results Compared with the I/R model mice,the leptin-treated mice had significantly lower neurological deficit scores,smaller cerebral infarct area,milder pathologies in the cortical brain tissue,and lessened cortical neuronal damage with normal morphology and less excessive proliferation of the astrocytes.Leptin treatment significantly up-regulated the expressions of GLT-1 and GLAST and lowered the content of glutamic acid in the brain tissue of the I/R mice.Conclusion Exogenous leptin has obvious neuroprotective effect against cerebral I/R injury in mice,mediated probably by controlling excessive astrocyte proliferation and up-regulating cortical GLT-1 and GLAST expressions to reduce glutamate-mediated excitotoxic injury of the astrocytes.

Objective To investigate the protective effect of exogenous leptin against focal cerebral ischemia-reperfusion(I/R)injury in mice and explore the underlying mechanism.Methods A total of 100 C57BL/6 mice were randomly divided into 5 groups,including a sham-operated group,cerebral I/R model group,and 3 leptin treatment groups with intraperitoneal injections of 0.5,1.0 or 2.0 leptin immediately after occlusion of the internal carotid artery.At 24 h after reperfusion,neurological function scores of the mice were assessed,and TTC staining was used to determine the area of cerebral infarction.The pathological changes in the cortical brain tissue of the mice were observed using HE staining,and degenerative damage of the cortical neurons were assessed with Fluoro-Jade C staining.The expression of glial fibrillary acidic protein in cortical brain tissues was detected using immunohistochemistry and Western blotting.In another 45 C57BL/6 mice with sham operation,I/R modeling,or leptin(1 mg/kg)treatment,glutamic acid in the cortical brain tissue was detected using glutamate assay,and cortical glutamate-aspartate transporter(GLAST)and glutamate transporter-1(GLT-1)protein expressions were detected using immunohistochemistry.Results Compared with the I/R model mice,the leptin-treated mice had significantly lower neurological deficit scores,smaller cerebral infarct area,milder pathologies in the cortical brain tissue,and lessened cortical neuronal damage with normal morphology and less excessive proliferation of the astrocytes.Leptin treatment significantly up-regulated the expressions of GLT-1 and GLAST and lowered the content of glutamic acid in the brain tissue of the I/R mice.Conclusion Exogenous leptin has obvious neuroprotective effect against cerebral I/R injury in mice,mediated probably by controlling excessive astrocyte proliferation and up-regulating cortical GLT-1 and GLAST expressions to reduce glutamate-mediated excitotoxic injury of the astrocytes.

ObjectiveBased on ultra performance liquid chromatography-mass spectrometry（UPLC-MS） and non-targeted metabolomics technology to discuss the central regulatory effect of Chaishao Liujuntang on chronic atrophic gastritis（CAG） rats with liver-depression and spleen-deficiency， and to look for the correlation between cerebral cortex， hypothalamus and metabolic status of gastric tissues. MethodA CAG rat model with liver-depression and spleen-deficiency was established by chemical induction， hunger and satiety disorders， chronic restraint and tail clamping stimulation， lasting for 16 weeks. Twenty-eight Wistar rats were randomly divided into a blank group of 8 rats and a model group of 20 rats. After the completion of modeling， 4 rats in the model group were taken to observe the pathological changes of gastric mucosa. The remaining model rats were randomly divided into a model group of 8 rats and a Chaishao Liujuntang group of 8 rats. Chaishao Liujuntang group rats were given 5.1 g·kg^-1 by gavage， and the remaining rats were given equal volume sterilized water by gavage for 4 weeks. Macroscopic characteristics， behavioral indicators and histopathological changes of the gastric mucosa of rats in each group were observed and compared. UPLC-MS non-targeted metabolomics was used to explore the metabolic regulation effect of Chaishao Liujuntang on the cerebral cortex， hypothalamus and stomach tissues of CAG rats with liver-depression and spleen-deficiency. Pearson correlation coefficient method was used to analyze the correlation between different tissue metabolites. ResultCompared with the model group， the macroscopic characteristics of rats in Chaishao Liujuntang group were improved， such as hair color， mental state and stool properties， and the number of times of crossing and standing in the open field experiment was significantly increased， and the static time of forced swimming was significantly reduced（P<0.01）， and the gastric mucosa atrophy was reduced. The metabolic data from the cerebral cortex of rats in each group identified a total of 3 common potential biomarkers， but not enriched in pathways， 26 common potential biomarkers were identified in the hypothalamus， and the key metabolic pathways involved were mainly enriched in purine metabolism， glycerol phospholipid metabolism， D-glutamine and D-glutamic acid metabolism. Seventeen common potential biomarkers were identified in the stomach， and the key metabolic pathways involved were mainly enriched in thiamine metabolism， valine， leucine and isoleucine biosynthesis， and taurine and taurine metabolism. Correlation analysis of metabolites in different tissues revealed that multiple amino acids and their derivatives mediated metabolic connections between the cerebral cortex， hypothalamus and stomach of rats. ConclusionThe metabolic disorders in the cerebral cortex， hypothalamus and stomach of CAG rats with liver-depression and spleen-deficiency have their own characteristics， mainly manifested by changes in the content of glycerol phospholipids， fatty acids and bile acid metabolites. Moreover， Chaishao Liujuntang may play a central regulatory role in CAG rats with liver-depression and spleen-deficiency by correcting the metabolic disorders of amino acids.

Objective:To systematically evaluate the efficacy of vitamin D (VD) in the treatment of male infertility.Methods:Randomized controlled trials (RCT) on male infertility treated with VD alone or in combination were identified and collected from PubMed, Embase, Web of science, CNKI, Wanfang and VIP databases. Patients were divided into experimental group (VD or combination therapy with VD as the main treatment) and control group (placebo treatment). A meta-analysis of the included studies was performed using RevMan5.4 software. The combined effect scale was calculated as the weighted mean difference ( MD) and its 95% CI. Results:Six RCTs with a total of 673 patients were ultimately included, and the study baseline was comparable. Total sperm motility ( MD=6.49, 95% CI: 2.75-10.22, P<0.001) and percentage of forward motile sperm ( MD=5.03, 95% CI: 1.36-8.70, P=0.007) were significantly different between the experimental group and control group. Total sperm count ( MD=5.56, 95% CI: -12.62-23.75, P=0.550), sperm concentration ( MD=-0.30, 95% CI: -4.81-4.21, P=0.890), semen volume ( MD=-0.04, 95% CI: -0.18-0.09, P=0.510) and normal sperm morphology ( MD=0.42, 95% CI: -0.05-0.88, P=0.080) were not significantly different between the experimental group and control group. Conclusion:VD is effective in improving semen quality in the treatment of male infertility. However, due to the limited number of samples included in RCT, clinical trials with larger samples are still needed to further confirm this thesis.

Objective:To identify risk variables for prolonged postoperative length of stay (PPOLOS) in hip fracture patients by machine learning algorithms and construct Nomogram models.Methods:A retrospective case-control study was conducted to select 248 patients with hip fracture diagnosed and treated in Yingtan 184th Hospital from June 2019 to June 2023 by convenient sampling method. Two machine learning algorithms were used (least absolute shrinkage and selection operator, LASSO and support vector machine-Recursive Feature Elimination, SVM-RFE) to screen PPOLOS risk variables. Construct a Nomogram model to predict the risk of PPOLOS in patients with hip fracture based on intersection risk variables. The model was validated using internal data sets.Results:Among the 248 patients with hip fracture, there were 79 males and 169 females, aged (64.49 ± 8.02). The mean postoperative length of hospital stay of 248 patients was (7.98 ± 5.68) d, and the median was 7 d. LASSO algorithm identifies 7 risk variables, the SVM-RFE algorithm identified 8 risk variables. Intersectional risk variables were age, body mass index (BMI), Charlson comorbidity index (CCI), type of surgery, and central granulocytocyte ratio (NLR). Multivariate Logistic regression analysis(intersection risk variables) showed that age [ OR=1.649(1.235-2.202)], BMI [1.603(1.204-2.134)], CCI [ OR=1.670(1.236-2.258)], type of surgery [ OR=1.620(1.209-2.170), 1.699(1.243-2.321)], and NLR [ OR=3.258(2.299-4.617)] were independently associated with the risk of PPOLOS (all P<0.05). The results showed that the conformity index of the Nomogram model was 0.865 (95% CI=0.768-0.945). The area under the curve was 0.852 (95% CI=0.748-0.962). When the risk threshold was >0.08, it could provide significant clinical net benefit. The clinical impact curve showed effective identification of PPOLOS patients in high-risk groups. Conclusions:This Nomogram model can guide medical staff to make clinical diagnosis and treatment decisions as soon as possible to avoid risks, allocate medical resources rationally, and improve nursing quality.

Objective:To systematically evaluate the efficacy of vitamin D (VD) in the treatment of male infertility.Methods:Randomized controlled trials (RCT) on male infertility treated with VD alone or in combination were identified and collected from PubMed, Embase, Web of science, CNKI, Wanfang and VIP databases. Patients were divided into experimental group (VD or combination therapy with VD as the main treatment) and control group (placebo treatment). A meta-analysis of the included studies was performed using RevMan5.4 software. The combined effect scale was calculated as the weighted mean difference ( MD) and its 95% CI. Results:Six RCTs with a total of 673 patients were ultimately included, and the study baseline was comparable. Total sperm motility ( MD=6.49, 95% CI: 2.75-10.22, P<0.001) and percentage of forward motile sperm ( MD=5.03, 95% CI: 1.36-8.70, P=0.007) were significantly different between the experimental group and control group. Total sperm count ( MD=5.56, 95% CI: -12.62-23.75, P=0.550), sperm concentration ( MD=-0.30, 95% CI: -4.81-4.21, P=0.890), semen volume ( MD=-0.04, 95% CI: -0.18-0.09, P=0.510) and normal sperm morphology ( MD=0.42, 95% CI: -0.05-0.88, P=0.080) were not significantly different between the experimental group and control group. Conclusion:VD is effective in improving semen quality in the treatment of male infertility. However, due to the limited number of samples included in RCT, clinical trials with larger samples are still needed to further confirm this thesis.

The delivery of exogenous insulin is very important for the treatment of type 1 and advanced type 2 diabetes.Traditional injectable administration is prone to cause hypoglycemia, while the intelligent insulin system has the advantages of safety, long-term effectiveness, and high responsiveness.Glucose oxidase (GOx) can consume O2 and catalyze glucose to produce gluconic acid and H2O2.Therefore, the O2 level, H2O2 content and pH of GOx system are closely related to the glucose level in the system.This review introduces the application of GOx in closed-loop insulin delivery systems at home and abroad in recent years, which can be divided into single response and multiple response of pH-response, hypoxia-response, and H2O2-response according to the mechanism.It also discusses the opportunities and challenge facing by the application of GOx in the future.