Lactic acid bacteria (LAB) are promising candidates for live bacterial drug delivery systems owing to their safety, probiotic properties, and ability to colonize the intestinal tract. At present, most research focuses on engineering LAB as carriers for the delivery of therapeutic proteins. As model organisms equipped with a versatile set of genetic tools, LAB can be readily modified to target various diseases and yield significant therapeutic effects. LAB-based carriers offer multiple advantages, including non-invasive delivery, ease of genetic manipulation, and suitability for large-scale production. Consequently, the use of LAB as recombinant protein expression vectors has attracted extensive research interest worldwide. The foundational principles, strategies for enhancing bioavailability, genetic engineering approaches, and the current research and application status of LAB-based drug delivery systems were summarized in this paper.

Objective To investigate the ameliorative effects and mechanisms of six types of tea(green tea,cyan tea,red tea,white tea,black tea and yellow tea)on metabolic disorders in obesity mice induced by high-fat diet(HFD).Methods Four-week-old male C57BL/6J mice were randomly divided into 8 groups with 7 mice per group.An HFD-induced obese mouse model was established,and the mice in control group maintained on standard diet followed by intragastric administration of different teas for 5 weeks.The body weight,liver weight ratio,fasting blood glucose,and lipid profile of the mice were measured to assess glucose and lipid metabolism.Serum inflammatory factors including IL-6,tumor necrosis factor-alpha(TNF-α)and oxidative stress markers[malondialdehyde(MDA)and superoxide dismutase(SOD)were measured.Additionally,liver histopathology and the expression of key glycolipid metabolism-related genes,adenosine monophosphate-activated protein kinase(AMPK)and carnitine palmitoyltransferase 1(CPT-1),were analyzed to explore underlying mechanisms.Results Cyan tea significantly suppressed weight gain,demonstrating superior weight control.White tea markedly reduced fasting blood glucose levels and decreased the area under the curve of oral glucose tolerance test(OGTT)and insulin tolerance test(ITT),indicating synergistic improvements in glucose metabolism and insulin sensitivity.Yellow tea exhibited exceptional anti-inflammatory and antioxidant effects,reducing hepatic IL-6 and MDA while enhancing SOD activity.Green tea activated the lipid oxidation pathway by upregulating AMPK/CPT-1 expression.All kinds of tea significantly attenuated hepatic lipid droplet accumulation.Conclusion All six types of tea alleviated metabolic disorders by reducing hepatic fat content in obesity mice.However,different types of tea exert their unique effects on improving metabolic disorders through differential mechanisms such as glucose metabolism regulation,lipid oxidation,and anti-inflammatory and antioxidant actions.

Objective:To investigate the association between adiponectin-related copy number variation (CNV) region (CNVR) and gestational diabetes mellitus (GDM).Methods:Pregnant women who had prenatal screening in Anqing Municipal Hospital, Anhui Province, from February 2018 to December 2020 were surveyed for baseline information collection, and blood samples were collected. The outcome information was obtained by post pregnancy follow-up. Latex-enhanced immunoturbidimetry and ASA-CHIA chip were used to detect serum adiponectin levels and CNV of pregnant women, respectively. After genotyping, CNV data were processed with software PennCNV 1.0.5 following standard quality control procedure. CNVR were identified and integrated by using software R 4.3.3. Then the associations between CNVR and adiponectin was evaluated, and gene annotation and over-representation analysis were conducted. The log-binomial regression model was used to adjust relevant covariates and analyze the association between adiponectin-related CNVR and GDM.Results:The detection rate of GDM was 9.54% (176/1 845) in the pregnant women. The genotyping information of 1 840 people (99.73%) passed quality evaluation. A total of 33 878 CNVs were identified, and 1 449 CNVRs were obtained after integration. After the false discovery rate method correction, CNVR_132 (CHR2: 47611743-47635062), CNVR_254 (CHR3: 10182703-10183872), CNVR_691 (CHR7: 150637053-150834539) and CNVR_1101 (CHR14: 104248431-104830620) were correlated with adiponectin levels (all P<0.05). Over- representation analysis showed that the molecular function of ribonucleotide binding [Gene Ontology (GO): 0032553] was significantly enriched based on the GO database. The log-binomial regression model, adjusting age, pre-pregnancy BMI, history of miscarriage, smoking history, and family history of diabetes, indicated that CNVR_132 (CHR2: 47611743-47635062) and CNVR_1101 (CHR14: 104248431-104830620) were not statistically associated with the risk for GDM (both P>0.05). However, CNVR_254 (CHR3: 10182703-10183872, a RR=1.83, 95% CI: 1.15-2.91) and CNVR_691 (CHR7: 150637053-150834539, a RR=1.73, 95% CI: 1.23-2.43) might be associated with an increased risk for GDM (all P<0.05). Conclusion:Adiponectin-related CNVR_254 (CHR3: 10182703-10183872) and CNVR_691 (CHR7: 150637053-150834539) might be risk factors for the incidence of GDM.

In recent years, prone mechanical ventilation has been widely used to improve oxygenation dysfunction in critically ill patients. During prone mechanical ventilation, the patient's face is compressed for a long time, and due to the difficulty in changing, facial pressure injuries and ocular complications are common and severe. These complications increase patient discomfort, reduce their tolerance and compliance with prone ventilation, and even cause tracheal tube displacement or dislodgement, leading to significant clinical challenges. In order to change this situation, the medical staff of the department of critical care medicine of the Second People's Hospital of Hengshui and the department of critical care medicine of Harrison International Peace Hospital had developed an adjustable facial support pad for prone ventilation, and obtained a National Utility Model Patent of China (ZL 2022 2 3295294.4). The device is composed of a facial support platform, a supporting telescopic foot frame and so on. There are front, back, left and right adjustable tracks below the support cushion platform, which can be adjusted to the best state suitable for the patient's face shape, which can alleviate the facial pressure injuries and ocular complications caused by the different sizes of each patient's face, improve the patient's comfort, and reduce the incidence of facial pressure injury and the occurrence of ocular complications of the patient. The height of the platform is adjusted by the telescopic feet, and there is a hook assembly below, which can be fixed by the clamp of the ventilator tubing, so as to prevent the ventilator tubing from pulling the endotracheal intubation due to the gravity of condensation, resulting in the displacement or even prolapse of the tracheal intubation, and reducing the occurrence of adverse events of tracheal intubation. It is worth promoting in the clinic.
Humans ; Respiration, Artificial/methods* ; Prone Position ; Equipment Design ; Face

To investigate the effects of zearalenone(ZEA)on the proliferation and apoptosis of sika deer antler chondrocytes,the chondrocytes were isolated and cultured in vitro and treated with 50μmol/L ZEA for 24 h.Flow cytometry was used to assess cell proliferation,cell cycle,apoptosis,mitochondrial membrane potential,and intracellular levels of reactive oxygen species(ROS).The expression changes of hypertrophic cartilage cell marker genes Col X,Runx2,Alpl,and apoptosis-related genes Casp-3,Bax,Bcl-2 were measured using quantitative PCR.Additionally,glutathione reductase(GR)activity and the levels of the oxidative stress marker malondialdehyde(MDA)were determined.The results showed that after 24 h of ZEA treatment,cell proliferation was sig-nificantly inhibited,with an increase in the number of cells in the G0/G1 phase and a decrease in the S phase.The expression levels of hypertrophic chondrocyte marker genes Col X,Runx2 and Al-pl were significantly increased.Apoptosis rate was significantly increased,with elevated expression of pro-apoptotic genes Casp-3,Bax and reduced expression of the anti-apoptotic gene Bcl-2.The content of MDA in the antler chondrocytes increased,ROS levels rose,and GR activity decreased.The mitochondrial membrane potential reduced.The results suggested that ZEA could inhibit the proliferation of antler chondrocytes and promote the apoptosis by regulating cellular oxidative stress responses and the expression of apoptosis-related genes.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

6-Thioguanine(6-TG)is an antineoplastic agent used in treatment of acute leukemia.However,significant interindividual variability in dosing regimens and frequent clinical manifestations of hepatotoxicity and myelosuppression as adverse effects have affected its therapeutic efficacy.Consequently,the development of rapid analytical methods for 6-TG in clinical samples,enabling continuous therapeutic drug monitoring of plasma concentrations,holds substantial significance in optimizing dosage regimens,mitigating adverse reactions,and investigating drug metabolism mechanisms.In this study,multi-tipped gold nanostars(AuNSs)were prepared.With bis-(p-sulfonylphenyl)phenylphosphine molecule as the protecting agent and internal standard molecule,the AuNSs were assembled onto a highly sensitive surface-enhanced Raman(SERS)substrate for developing a ratio-based SERS quantitative analysis method for 6-TG in serum.The AuNSs containing multiple tips and gaps exhibited strong local surface plasmon resonance effect and SERS activity,ensuring the sensitivity of the analytical method.Furthermore,the introduction of internal standard molecules could improve the reproducibility,which guaranteed this method suitable for rapid analysis of drug molecules in complex samples.Quantitative analysis of 6-TG was achieved with linear detetion range of 1.0×10?4-1.0 mmol/L.In the spiked recovery experiments of serum,the RSD was less than 5.32%,and the recoveries were 94%-104%,which proved that this method could be used for rapid quantitative determination of 6-TG in serum.This method provided a powerful tool for studying drug pharmacokinetics,which could promote the optimization of the usage methods of anti-cancer drugs,and it was expected to further enhance the clinical efficacy and safety of 6-TG,enabling it to achieve the best therapeutic effect.

Objective To analyze the correlation between inflammation indicators(systemic inflammatory response syndrome and systemic immune-inflammation index)and adverse outcomes in patients with symptomatic stroke during hospitalization.Methods This study was a prospective cohort study including consecutive patients with symptomatic stroke who were hospitalized in Fuwai Hospital from January to September 2023.The past medical history,clinical symptoms and signs of the patients were collected.The neurological damage was evaluated with National Institute of Health Stroke Scale(NIHSS).Laboratory test results were recorded and the SIRI and SII in-dex were calculated.Patients were followed up for 90 days after the stroke,and their neurological outcomes were evaluated using the modified Rankin Scale.A score of 0-1 was classified as good outcome,and a score ≥2 was classified as poor outcome.The correlation between inflammatory response indicators and poor outcomes was as-sessed using multiple Logistic regression.Results A total of 97 patients with in-hospital symptomatic stroke were included with an average age of 61.8±12.7 years.Among them,there were 28 females(28.9％,28/97),9 with a history of prior stroke(9.3％,9/97),15 with atrial fibrillation(15.5％,15/97),16 with heart failure(16.5％,16/97),and 7 with myocardial infarction(7.2％,7/97).Correlation analysis showed that the NIHSS score at the time of stroke onset was significantly correlated with the patient's post-stroke SIRI(r=0.237,P＜0.05)and SII(r=0.234,P＜0.05).After 90 days of follow-up,41 cases(42.3％,41/97)had a poor outcome.Multiple Logistic regression analysis showed that post-stroke SIRI(Or=4.71,95％CI:1.24-17.90)and SII(Or=3.13,95％CI:0.88-11.06)were correlated with poor outcomes within 90 days after the stroke.Analysis using restricted cubic splines showed that as the levels of SIRI and SII increased,the risk of poor out-comes in patients with in-hospital symptomatic stroke increased.Conclusions SIRI is an independent risk factor for poor outcomes in patients with in-hospital symptomatic stroke,and the risk of poor neurological outcomes in-creases with high level of SIRI.

Objective:To investigate the effect and safety of the double-cross dressing technique for composite rhytidectomy.Methods:A retrospective analysis was performed on a total of 121 patients with face and neck ageing, who were admitted to the Facial and Neck Plastic Surgery Center, the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences from June 2020 to May 2023, all female with the age ranged 34-72 years old. All the patients underwent a full facial and neck composite rhytidectomy. Immediately after surgery, a double-cross bandaging was applied. The cotton pad was nested on the outer auricle, so that the front of the ear and the back of the ear were the first cross. This cross aimed to accurately pressurized the temporal, buccal region and postauricle flap. The second cross occurred at the radix. It secured composite tissue flap at the zygomatic arch and the buccal fat pad zone. Patient′s external auricle was not compressed after bandaging. The healing and the occurrence of complications were observed.Results:All the patients were satisfied with the comfort of the bandaging, the satisfied rate was 100% (121/121). All the patients had different degrees of periocular and perioral swelling 72 hours after surgery. Conjunctival edema and xanthochromia occurred in 30 patients, and oral mucosal congestion occurred in 25 patients, all of which were spontaneously resolved 2-4 weeks after surgery. Postoperative nursing was easily managed. There were no events such as dressing loosening, blocked draining tubes, and difficulty in replacing tubes. All the patients were followed up for 3-12 months after surgery, the flap in the postauricular area of all patients healed well, and there were no adverse complications such as wound infection, necrosis of the flap in the operative area, and delayed healing of the incision.Conclusion:The double-cross bandaging technique achieves the comfort bandaging and good protection of the face, which is safe and effective.