ObjectiveTo investigate the mechanisms by which the combination of berberine （BBR） and baicalin （BAI） ameliorates type 2 diabetes mellitus （T2DM） due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group （n=10） and a T2DM （syndrome of internal accumulation of dampness-heat） fecal microbiota transplantation group （n=20）. The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage， respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group （n=8） and a BBR-BAI group （n=11）. BBR was administrated at a dose of 200 mg·kg^-1， and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， insulin （INS）， triglycerides （TG）， total cholesterol （CHOL）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1， zonula occludens-1 （ZO-1）， and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to assess the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS）， respectively. ResultsThe BBR-BAI combination lowered the FBG， HbA1c， and INS levels （P<0.05， P<0.01） and alleviated insulin resistance （P<0.01） in T2DM mice. Additionally， BBR-BAI elevated the levels of ZO-1， occludin， and claudin-1 （P<0.05， P<0.01） and down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in the colon （P<0.05， P<0.01）. The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus， Phascolarctobacterium， and Akkermansia （P<0.05）， while significantly decreasing the relative abundance of Alistipes， Odoribacter， and Colidextribacter （P<0.05）. UPLC-Q-TOF-MS identified 28 differential metabolites， which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.

Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

Objective:To explore the application of the semi-flipped classroom combined with knowledge point auction learning method in the theoretical teaching among stomatological students and its effectiveness.Methods:Undergraduates from four classes at Guanghua School of Stomatology, Sun Yat-Sen University were taken as research subjects. Students from two classes ( n=198) were taught using the semi-flipped classroom combined with the knowledge point auction learning method, while students from the other two classes ( n=172) were taught with the regular classroom teaching method as controls. Classroom quizzes were used to compare the two classes' mastery of important and difficult points, and a questionnaire was used to investigate students' feedback on the class outcomes. SPSS 22.0 was used for the independent samples t-test. Results:The mean test score of the experimental class was higher than that of the control class (88.51±11.02 vs. 80.40±8.53). The results of the questionnaire showed that students' interest in the course, comprehension and absorption of knowledge points, degree of satisfaction with the class, and mastery of the contents in sections in the experimental class were significantly higher than those in the control class (7.28±1.51 vs. 9.10±0.73, 6.92±1.44 vs. 8.69±1.62, 6.09±1.87 vs. 7.61±1.46, 6.40±1.04 vs. 7.70±0.86 ).Conclusions:The semi-flipped classroom combined with the knowledge point auction learning method is innovative and achieves good teaching outcomes. It holds promise for wider use in the theoretical teaching of various clinical subjects. To explore the application of the semi-flipped classroom combined with knowledge point auction learning method in the theoretical teaching among stomatological students and its effectiveness.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Background Vascular endothelial injury is an important pathogenic step of vibration-induced hand arm vibration disease (HAVD), and long-term vibration exposure can lead to vascular endothelial cell dysfunction and cell damage. Cell ferroptosis may be one of the important mechanisms of vibration-induced vascular endothelial cell injury and HAVD. Objective To explore whether vibration can induce changes in ferroptosis-related indicators in vascular endothelial cells in vitro. Methods Human umbilical vein endothelial cells (HUVEC) were divided into four vibrationgroups and two control groups. The vibration groups were exposed to an vibration setting of 125 Hz, 6.5 m·s⁻² frequency band and for different durations: 1 d 2 h (total 1 d, 2 h per day), 1 d 4 h (total 1 d, 4 h per day), 2 d 2 h (total 2 d, 2 h per day), and 2 d 4 h (total 2 d, 4 h per day), respectively. All control groups were treated the same as the experimental groups except no vibration exposure. When the cells were 80% confluent, the control groups and the corresponding experimental groups were harvested at the same time. The effects of subgroup treatments on iron, reduced glutathione (GSH), and malondialdehyde (MDA) in HUVEC were detected with a cell ferrous colorimetric test kit, a reduced GSH colorimetric test kit, and a trace MDA test kit, respectively. Real-time quantitative polymerase chain reaction (RT-PCR) was used to detect the mRNA expressions of ferroptosis-related genes acyl-CoA synthetase long chain family member 4 (ACSL4), tumor protein 53 (P53), recombinant human ferritin heavy chain (FTH1), and glutathione peroxidase 4 (GPX4). Western blot (WB) was used to detect the expression levels of ferroptosis-related proteins in HUVEC. Results Compared with the control groups, the vibration induced an increase in the iron content of HUVEC with a dose-response trend. Compared with the control groups, the reduced GSH content of HUVEC in the vibration group decreased with the increase of vibration time and frequency, and there was a dose-response trend. Compared with the control groups, the intracellular MDA content of HUVEC in the 1 d 2 h, 1 d 4 h, and 2 d 4 h vibration groups increased, and the MDA content in the 1 d 2 h and 1 d 4 h vibration group increased with time. The RT-PCR results showed that the mRNA expression levels of ACSL4 and P53 in the 1 d 4 h group increased compared with the 1 d 2 h group. Compared with the 2 d control group, the mRNA expression levels of ACSL4 in the 2 d 2 h vibration group and the 2 d 4 h vibration group increased, and the mRNA expression level of P53 in the 2 d 4 h vibration group increased. Compared with the 1 d control group, the mRNA expression levels of FTH1 and GPX4 in endothelial cells in the vibration 1 d 2 h group decreased. The WB results showed that compared with the control groups, the expression level of ferroptosis-related protein ACSL4 in endothelial cells increased in the vibration 1 d 2 h group; the expression levels of P53 in the 1 d 2 h and 2 d 4 h vibration groups increased; the expression levels of GPX4 decreased in the 1 d 4 h and 2 d 2 h vibration group, and the decrease was more obvious in the 2 d 2 h vibration group than in the 1 d 2 h vibration group; the above differences were statistically significant (P<0.05). Conclusion Vibration induces an increase in iron content, a decrease in GSH, and an increase in MDA in vascular endothelial cells in vitro, as well as mRNA and protein expressions of ferroptosis-related genes ACSL4, P53, FTH1, and GPX4.

Tumors represent one of the primary threats to human life, with the dissemination of malignant tumors being a leading cause of mortality among cancer patients. Early diagnosis of tumors can reliably predict their progression, significantly reducing mortality rates. Tumor markers, including circulating tumor cells, exosomes, proteins, circulating tumor DNA, miRNAs and so on, generated during the tumor development process, have emerged as effective approach for early tumor diagnosis. Several methods are currently employed to detect tumor markers, such as polymerase chain reaction, Northern blotting, next-generation sequencing, flow cytometry, and enzyme-linked immunosorbent assay. However, these methods often suffer from time-consuming process, high costs, low sensitivity, and the requirement for specialized personnel. Therefore, a new rapid, sensitive, and specific tumor detection method is urgently needed.The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) system, originating from the adaptive immune system of bacteria, has found extensive applications in gene editing and nucleic acid detection. Based on the structure and function of Cas proteins, the CRISPR/Cas system can be classified into two classes and six types. Class I systems consist of multiple Cas protein complexes, including types I, III, and IV, while Class II systems comprise single, multi-domain Cas proteins mediated by RNA, including types II (Cas9), V (Cas12), and VI (Cas13). Class II systems have been widely employed in the fields of biotechnology and nucleic acid diagnostics due to their efficient target binding and programmable RNA specificity. Currently, fluorescence method is the most common signal output technique in CRISPR/Cas-based biosensors. However, this method often requires the integration of signal amplification technologies to enhance sensitivity and involves expensive and complex fluorescence detectors. To enhance the detection performance of CRISPR/Cas-based biosensors, the integration of CRISPR/Cas with some alternative techniques can be considered. The CRISPR/Cas integrated electrochemical sensor (E-CRISPR) possesses advantages such as miniaturization, high sensitivity, high specificity, and fast response speed.E-CRISPR can convert the reactions between biomolecules and detecting components into electrical signals, rendering the detection signals more easily readable and reducing the impact of background values. Therefore,E-CRISPR enhances the accuracy of detection results. E-CRISPR has been applied in various fields, including medical and health, environmental monitoring, and food safety. Furthermore, E-CRISPR holds tremendous potential for advancing the detection levels of tumor markers.Among all types of Cas enzymes, the three most widely applied are Cas9, Cas12, and Cas13, along with their respective subtypes. In this work, we provided a brief overview of the principles and characteristics of Class II CRISPR/Cas single-effector proteins. This paper focused on the various detection technologies based on E-CRISPR technique, including electrochemical impedance spectroscopy, voltammetry, photoelectrochemistry, and electrochemiluminescence. We also emphasized the applications of E-CRISPR in the field of tumor diagnosis, which mainly encompasses the detection of three typical tumor markers (ctDNA, miRNA, and proteins). Finally, we discussed the advantages and limitations of E-CRISPR, current challenges, and future development prospects. In summary, althoughE-CRISPR platform has made significant strides in tumor detection, certain challenges still need to be overcome for their widespread clinical application. Continuous optimization of the E-CRISPR platform holds the promise of achieving more accurate tumor subtyping diagnoses in clinical settings, which would be of significant importance for early patient diagnosis and prognosis assessment.

Objective To establish an evaluation criterion for high-quality nursing services in comprehensive hospitals of Grade Three in Guangdong Province and provide references for promoting the evaluation of high quality nursing services and standardising high quality nursing services.Methods Based on literature review,brainstorming and references of relevant domestic systems,standards and policies,a pool of evaluation index items and a preliminary questionnaire were constructed.Delphi method was used for two rounds of expert consultations on evaluation indicators.Results The positive coefficients of the two rounds of expert consultations were of 80.00%and 91.67%,respectively,with the authority coefficients both at 0.93.The Kendall coordination coefficients for hospital part were 0.128 and 0.116 respectively,for ward part were 0.193 and 0.107 with statistical differences(both P＜0.001).The evaluation criteria for high-quality nursing services in general hospitals above the third level in Guangdong Province involved in nursing services of hospitals and wards.There were 8 primary indicators,22 secondary indicators and 65 tertiary indicators in the nursing services at hospital part,and 9 primary indicators,23 secondary indicators and 50 tertiary indicators in the nursing services at ward part.Conclusions The evaluation criteria for high-quality nursing services in comprehensive hospitals above the third level in Guangdong Province,established in this study,are scientifically valid and reliable.They allow improvement of management system for the high-quality nursing services as well as guide the healthy development of high-quality nursing services.

Objective:To investigate the clinicopathological and molecular genetic features of POLE mutant endometrioid carcinoma.Methods:Genetic test data of 230 cases of endometrial carcinoma that underwent surgical resection and molecular typing by next generation sequencing in the First Medical Center of Chinese PLA General Hospital from January 2021 to June 2023 were retrospectively analyzed. Seventeen cases of endometrioid carcinoma with POLE mutation were selected. Clinical and prognostic information was collected. The paraffin-embedded tissue and immunohistochemical sections were reviewed, and the gene detection data were analyzed.Results:In the 17 cases of endometrioid carcinoma with POLE mutations, 16 cases (16/230, 6.9%) had mutations at known pathogenic sites, and 1 case had a mutation site (S459Y) that had not been reported, which was inferred to be pathogenic based on clinical prognosis. The 17 patients aged from 48 to 79 years (median 56 years, mean 58 years). All cases had typical histological features of endometrioid carcinoma, including 7 cases (7/17) of poorly-differentiated, 4 cases (4/17) of moderately-differentiated and 6 cases (6/17) of well-differentiated. Squamous differentiation was noted, mucous differentiation was less commonly found and often accompanied by superficial muscle infiltration. The number of stromal lymphocyte infiltration was variable. Lymph-vascular embolus was found in 6 cases, and lymph node metastasis was only detected in 1 case. According to the FIGO staging system for endometrial cancer in 2023, all the cases were in FIGO stage ⅠA m-POLEmut except for one case in FIGO stage ⅢC1. There were 8 cases with genetic co-mutation, 5 cases with TP53 mutation (immunohistochemically subclonal expression pattern), 1 case with MSI-H, and 2 cases with both TP53 mutation and MSI-H. Five of 7 patients with POLE mutation (poorly-differentiated) received postoperative chemotherapy and/or radiotherapy, 4 patients received endocrine therapy, and 8 patients had no treatment after surgery. One of the stage ⅠA m-POLEmut tumor patients was found to have pelvic recurrence one year after surgery, and the other 16 patients were followed up for 10-38 months without recurrence or metastasis. Conclusions:POLE mutant endometrioid carcinoma may have different differentiation, and most patients have good prognosis. Correct interpretation of molecular results, accurate identification and classification are important for predicting prognosis and avoiding overtreatment. However, a small number of cases may have recurrence and metastasis, and therefore it is necessary to make a reasonable treatment plan based on the comprehensive judgment of other high risk factors.

Congenital disorder of glycosylation type Id(CDG-Id)is due to a variation in the ALG3 gene that results in a defect in the encoded alpha-1,3-mannosyltransferase.The pregnant woman in this case was 32 years old,G7P1,whose fifth singleton pregnancy had fetal malformations suggested by ultrasound at another hospital.After termination of pregnancy,she came to Obstetrics and Gynecology Hospital,Fudan University for genetic testing,with the result of ALG3 gene variants[NM_005787:c.67C>T(p.Gln23*),Heterozygote,Paternal;NM_005787:c.1188G>A(p.Trp396*),Heterozygote,Maternal].In this singleton pregnancy at 21 weeks of gestation,prenatal ultrasound at our hospital demonstrated multiple fetal malformations,including micrognathia,cerebellar vermis absence,cystic occupancy of the posterior cranial fossa,all long bones of the limbs being short,scoliosis and stiffness of the finger joints as the main manifestations.The pregnancy was then terminated at another hospital,and subsequent genetic testing results confirmed that it was also due to ALG3 gene variants.This article focuses on the prenatal ultrasound manifestations and genetic features of CDG-Id,in order to improve the understanding of this disorder.

Professor ZHOU Peng has deeply discussed the pathological characteristics of psoriasis vulgaris,emphasizing that the disease is usually manifested deficiency interweaved with excess,leading to frequent recurrence and persistent refractory,which may lead to psychological and emotional problems of patients.This paper further expounds the effect of blood stasis on the pathogenesis,progression and prognosis of psoriasis,and puts forward a new method of combining Lingnan fire needling and filiform needling acupuncture technique to treat psoriasis vulgaris with blood stasis syndrome.Professor ZHOU Peng believes that the treatment principle of this disease is"regulating the mind first,rectifying blood as a base,syndrome differentiating and eliminating pathogenic factors",aiming at comprehensively considering the etiology and symptoms,in order to achieve more effective treatment results.Combined with the analysis of dermoscopic signs,it provides a possible improvement direction for the treatment of psoriasis vulgaris from a new perspective.