Proteolysis-targeting chimeras (PROTACs) have emerged as a promising therapeutic strategy for targeted protein degradation. However, the clinical application of PROTACs may be hindered by off-target toxicity resulting from non-tissue-specific protein degradation and ingenious prodrug strategies may open new avenues to addressing this concern. Herein, we propose a light-induced positive feedback strategy to use photodynamic therapy (PDT) to improve the activation efficiency of PROTAC prodrugs, monitor PROTAC release, and combine PROTAC to induce tumor cell apoptosis. In the hypoxic tumor microenvironment, the azo bond in AZO-PRO selectively cleaves, triggering the release of the potent protein degrader PRO and the multifunctional photosensitizer. Once activated, the fluoresce signal of the photosensitizer dramatically recovers, allowing monitoring of prodrug activation. Additionally, upon irradicating the tumor site using near-infrared (NIR) laser, PDT exacerbates tumor hypoxia, further promoting AZO-PRO activation. Our work introduces a novel approach to efficiently track and activate PROTAC prodrugs, enhance their antitumor efficacy, and mitigate off-target systemic toxicity.

Objective To investigate the changes in the gut microflora(GM)composition and metabo-lites in children with allergic rhinitis(AR)based on high-throughput sequencing technology.Methods From December 2023 to May 2024,11 preschool children with allergic rhinitis(AR)who visited the pediatric outpa-tient department of Shantou University Medical College Longgang Maternal and Child Health Hospital Clini-cal College(Longgang District Maternal and Child Health Hospital)were selected as the AR group,and 21 healthy children of the same age who underwent physical examinations in the child health care department during the same period were selected as the control group.Fecal samples were collected from both groups,and DNA was extracted and amplified.High-throughput sequencing technology was used to analyze the composi-tion of gut microbial genes,and the differences in gut microbiota composition and metabolites between the two groups were compared.Results Compared with the control group,the AR group had a higher Shannon index,with a significant increase in the abundance of Proteobacteria and Saccharibacteria.The relative abundance of Veillonella,Enterococcus,Escherichia coli/Shigella,Haemophilus,and Streptococcus was significantly high-er,while the relative abundance of Lachnospira,Anaerostipes,Enterobacteriaceae,Anaerobacterium,and Eu-bacterium was significantly lower(P＜0.05).There were statistically significant differences in the principal components of GM metabolites between the two groups(P＜0.05).A total of 2 540 different metabolites were identified,of which 1 185 metabolites were significantly increased,20 metabolites were significantly de-creased,and 1 335 metabolites showed no significant changes.Variable importance in projection(VIP)analy-sis revealed 30 significantly different metabolites.Compared with the control group,2 fecal metabolites were significantly downregulated in the AR group,specifically 3-furanmethanol glucoside and membrane heptosyl A.Conclusion The gut microbiota of preschool children with AR has undergone significant changes,which are related to inflammation and immune function.

Objective:To develop a validation method for microbial targeted next generation sequencing (tNGS) detection for respiratorypathogens, and to evaluate the performance of the pathogen-targeted high-throughput sequencing test implemented in local hospital.Methods:Cross-sectional study. A total of 14 patients with severe pulmonary infections were admitted to Huangshi Central Hospital from December 2023 to January 2024. Samples were collected as follows:Bronchoalveolar lavage fluid (BALF) samples ( n=7) subjected to culture, fluorescent PCR, and tNGS testing. Sputum samples ( n=2) analyzed via sputum culture, fluorescent PCR, and tNGS. Throat swab samples ( n=5) tested using fluorescent PCR-capillary electrophoresis and tNGS. Reference samples were prepared using representative species such as Influenza A virus, Adenovirus C, Klebsiella pneumoniae, Aspergillus fumigatus, Staphylococcus aureus, Staphylococcus epidermidis, Candida parapsilosis, and Candida albicans. Jurkat cells at different concentrations were used as a source of human cells. Traditional detection methods such as fluorescent PCR-capillary electrophoresis and culture methods were used as reference methods. The detection performance of tNGS was evaluated by assessing the detection limit, precision, human cell impact, stability, cross-reactivity, and accuracy of metagenomic next-generation sequencing for pathogen detection. Results:The detection limits for Klebsiella pneumoniae, Human Adenovirus C, and Influenza A virus were 2×10 2 copies/ml, and for Aspergillus fumigatus, Staphylococcus aureus, Staphylococcus epidermidis, Candida parapsilosis, and Candida albicans, the detection limits were 4×10 2 copies/ml. The consistency rate of repeated detection results for all pathogens in the reference samples was 100%. The impact assessment experiment of human cells showed that when the concentration of Jurkat cells reached 1×10 6 cells/ml, Influenza A virus, Adenovirus C, Klebsiella pneumoniae, and Aspergillus fumigatus could all be detected. Stability experiments showed that there was no significant change in the number of pathogen sequences after the specimens were stored at 4 ℃ and -20 ℃ for 1 day, 4 days, and 7 days, respectively. Cross-reactivity experiments showed that when the concentration ratios of Staphylococcus aureus, Staphylococcus epidermidis, Candida parapsilosis, and Candida albicans were (5∶1∶1∶5), (1∶5∶5∶1), and (1∶1∶1∶1), respectively, the detection rate of closely related microbial species was 3/3. Accuracy assessment showed that the accuracy of 19 clinical specimens was 18/19 cases. Conclusion:Compared with traditional detection methods as the reference, tNGS demonstrates high sensitivity and a high positive concordance rate, underscoring its significant clinical value in the detection of respiratory pathogens.

Objective To summarize the role of clinical pharmacists in pharmaceutical care in the treatment of patients with pneumocystis jirovecii pneumonia secondary to immune-mediated colitis.Methods The association of immune-mediated colitis induced by serplulimab was evaluated by clinical pharmacist,anti-infective regimen for pneumocystis jirovecii pneumonia was put forward,addressed concerns regarding the impact of trimethoprim/sulfamethoxazole on the efficacy of fecal microbiota transplantation,pharmaceutical care for whole therapeutic process of the patient was monitored.Results Through pharmaceutical care and collaborating with physicians,the patient's pneumocystis jirovecii pneumonia was significantly improved,and the clinical and endoscopic remission of immune-mediated colitis after two fecal microbiota transplantation were achieved.Conclusion To ensure the safety and effectiveness of immune-mediated colitis and pneumocystis jirovecii pneumonia for patients,clinical pharmacists should play the role of participation and pharmaceutical care.

Objective To summarize the role of clinical pharmacists in pharmaceutical care in the treatment of patients with pneumocystis jirovecii pneumonia secondary to immune-mediated colitis.Methods The association of immune-mediated colitis induced by serplulimab was evaluated by clinical pharmacist,anti-infective regimen for pneumocystis jirovecii pneumonia was put forward,addressed concerns regarding the impact of trimethoprim/sulfamethoxazole on the efficacy of fecal microbiota transplantation,pharmaceutical care for whole therapeutic process of the patient was monitored.Results Through pharmaceutical care and collaborating with physicians,the patient's pneumocystis jirovecii pneumonia was significantly improved,and the clinical and endoscopic remission of immune-mediated colitis after two fecal microbiota transplantation were achieved.Conclusion To ensure the safety and effectiveness of immune-mediated colitis and pneumocystis jirovecii pneumonia for patients,clinical pharmacists should play the role of participation and pharmaceutical care.

Objective:To develop a validation method for microbial targeted next generation sequencing (tNGS) detection for respiratorypathogens, and to evaluate the performance of the pathogen-targeted high-throughput sequencing test implemented in local hospital.Methods:Cross-sectional study. A total of 14 patients with severe pulmonary infections were admitted to Huangshi Central Hospital from December 2023 to January 2024. Samples were collected as follows:Bronchoalveolar lavage fluid (BALF) samples ( n=7) subjected to culture, fluorescent PCR, and tNGS testing. Sputum samples ( n=2) analyzed via sputum culture, fluorescent PCR, and tNGS. Throat swab samples ( n=5) tested using fluorescent PCR-capillary electrophoresis and tNGS. Reference samples were prepared using representative species such as Influenza A virus, Adenovirus C, Klebsiella pneumoniae, Aspergillus fumigatus, Staphylococcus aureus, Staphylococcus epidermidis, Candida parapsilosis, and Candida albicans. Jurkat cells at different concentrations were used as a source of human cells. Traditional detection methods such as fluorescent PCR-capillary electrophoresis and culture methods were used as reference methods. The detection performance of tNGS was evaluated by assessing the detection limit, precision, human cell impact, stability, cross-reactivity, and accuracy of metagenomic next-generation sequencing for pathogen detection. Results:The detection limits for Klebsiella pneumoniae, Human Adenovirus C, and Influenza A virus were 2×10 2 copies/ml, and for Aspergillus fumigatus, Staphylococcus aureus, Staphylococcus epidermidis, Candida parapsilosis, and Candida albicans, the detection limits were 4×10 2 copies/ml. The consistency rate of repeated detection results for all pathogens in the reference samples was 100%. The impact assessment experiment of human cells showed that when the concentration of Jurkat cells reached 1×10 6 cells/ml, Influenza A virus, Adenovirus C, Klebsiella pneumoniae, and Aspergillus fumigatus could all be detected. Stability experiments showed that there was no significant change in the number of pathogen sequences after the specimens were stored at 4 ℃ and -20 ℃ for 1 day, 4 days, and 7 days, respectively. Cross-reactivity experiments showed that when the concentration ratios of Staphylococcus aureus, Staphylococcus epidermidis, Candida parapsilosis, and Candida albicans were (5∶1∶1∶5), (1∶5∶5∶1), and (1∶1∶1∶1), respectively, the detection rate of closely related microbial species was 3/3. Accuracy assessment showed that the accuracy of 19 clinical specimens was 18/19 cases. Conclusion:Compared with traditional detection methods as the reference, tNGS demonstrates high sensitivity and a high positive concordance rate, underscoring its significant clinical value in the detection of respiratory pathogens.

Objective:To develop a perinatal depression screening scale for Chinese urban version and test its reliability and validity.Methods:Naturally conceived women who were≥12 weeks of gestation and had regular prenatal examinations or delivered within four weeks in Xi'an and Foshan were recruited using convenience sampling. Initial entries were created through clinical interviews and expert validation of 50 of these pregnancies. Further item screening and testing for reliability and validity using correlation analysis, critical ratio method, homogeneity test, and factor analysis were performed. The final questionnaire was formed and then used to test the subjects. Fifty women who had completed the questionnaire effectively were selected for retesting 10 to 15 days after the initial evaluation. A structural equation model was constructed using the Edinburgh Postpartum Depression Scale (EPDS) as the reference criterion to conduct the scale's exploratory and confirmatory factor analysis. The receiver operating characters curve was used to determine the cut-off point of the scale.Results:(1) 1 300 questionnaires were issued, and 1 049 valid questionnaires were received with a recovery rate of 80.7%. Among them, 601 were used for exploratory and correlation analysis, and 448 were used for confirmatory factor analysis. (2) The initial entries of the scale totaled 63. After eliminating indicators that did not meet the requirements for item analysis, the final scale consisted of 22 entries in total. The final scale consisted of six dimensions, including "abnormal mood", "loss of interest and pleasure," "sleep disorder," "self-blame and guilt," "decline in conscious thought ability," and "lack of energy". (3) The correlation coefficients between the above six dimensions and EPDS were 0.609, 0.322, 0.423, 0.522, 0.545, and 0.516, respectively. The one between the total scale and EPDS was 0.715 (all P<0.01). (4) The confirmatory factor analysis of each model and the scale showed an acceptable fit and a stable factor structure with indices Chi-square/degrees of freedom =2.504, square root of approximation error=0.058, standardized root mean square residual=0.048, comparative fit index=0.925, Tueker-Lewis index=0.911. After retaining 22 items, the Cronbach's coefficients of the six dimensions ranged from 0.708 to 0.870. (5) The test-retest reliability of the total scale, six dimensions, and 22 items were 0.936, 0.786-0.846, and 0.720-0.886, respectively. (6) The receiver operating characteristic curve of the scale was drawn with EPDS≥13 as the cut-off value, and the area under the curve (AUC) of EPDS was 0.808 (95% CI: 0.744-0.872). When the original cut-off point was 21, the Youden index was the max (0.561), with sensitivity and specificity of 0.952 and 0.609, respectively. The Kappa value was 0.691, indicating that the scale was consistent with EPDS. Conclusion:This study preliminarily established a Chinese urban version of the perinatal depression screening scale with a stable factor structure and good reliability and validity.

Objective To generate and identify the Itgbl1(integrin beta-like)promoter-driven Cre knock-in mouse line.Methods Itgbll-Cre knock-in mice were generated using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene editing.The Itgbl1-Cre mice were crossed with the Cre reporter ROSALSL-tdTomato)mice to detect the expression profile of Cre activity.The tdTomato expression pattern across tissues and cell-specific markers were used to identify the cell types of Itgbl1-expressing cells and their progeny.Results and Conclusion tdTomato was specifically expressed in mucous acinar cells of the sublingual gland,pancreatic islet cells,and gastric endocrine cells.In addition,tdTomato expression was also found in some of the neurons of the retina and brain,as well as in a few cells in the serosal layer of the intestine,articular cartilage,periosteum,and bone marrow.The first Itgbl1-Cre recombinase transgenic mouse line was established,which can specifically label the mucous acinar cells of the sublingual gland.

Objective To investigate the changes of blood lipid and glycosylated hemoglobin (HbA1c) levels in obese type 2 diabetes (T2DM) patients and their relationship with insulin resistance (Homa-IR). Methods A total of 120 cases of T2DM newly diagnosed in Motuo County, Tibet from February to October 2022 were selected as the observation group. According to BMI, the patients were divided into diabetes normal weight group (46 cases), overweight group (43 cases) and obesity group (31 cases); 145 healthy subjects were selected as the control group. The levels of HbA1c, fasting blood glucose (FPG), fasting insulin (FINS), serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) were detected in the study subjects, and Homa-IR and Homa-β indices were calculated. The height, weight, and abdominal circumference were measured. The differences in the levels of the above indicators between the observation group patients and the control group, as well as among various subgroups within the observation group were compared. The influencing factors of Homa-IR in obese T2DM patients were analyzed. Results Compared with the control group, a significant increase in BMI, abdominal circumference, blood pressure, HbA1c, FBG, FINS, TC, TG, LDL-C, UA, visceral fat area, and the levels of Home-IR and Home-β was found in the observation group (all P<0.05). There were significant differences in BMI, abdominal circumference, and the levels of FINS, Homa IR, Homa-β, and HbA1c in diabetes patients with different BMI (all P<0.05). Correlation analysis showed that TG levels in obese T2DM patients in the observation group were significantly correlated with HbA1c (r=0.396, P=0.027), Homa-IR (r=0.405, P=0.024), and Home-β (r=-0.401, P=0.025); LDL-C was significantly correlated with Homa-IR (r=0.411, P=0.022) and Homa-β (r=-0.412, P=0.021); HbA1c was significantly positively correlated with BMI (r=0.371, P=0.040). Conclusion Insulin resistance is closely related to TG, LDL-C, and BMI in obese T2DM patients from the Motuo ethnic minority of Tibet, suggesting that these factors may play a role in the occurrence of T2DM.

Objective To evaluate the effectiveness and safety of edaravone combined with oxiracetam in the treatment of acute cere-bral infarction.Methods PubMed,Embase,Cochrane Library,CNKI,Wanfang Data and other databases were comprehensively searched from database inception until October 27,2022,to collect randomized controlled trials of edaravone combined with oxiracetam in the treatment of acute cerebral infarction(ACI).RevMan5.4software was used to analyze the collected data.Results A total of9studies involving 887 patients were included.Meta-analysis results showed that the overall effective rate and Barthel index in the observation group were significantly higher than those in the control group(OR=4.66,95％CI:2.74-7.93,P＜0.001;MD=14.57,95％CI:8.58-20.56,P＜0.001),the NIHSS scores in the observation group were significantly lower than that in the control group(MD=-5.28,95％CI:-6.42--4.13,P＜0.001).There was no significant difference in adverse effect rate between the two groups(RR=1.11,95％CI:0.63-1.95,P=0.72).Conclusion The combination of edaravone and oxiracetam in the treatment of ACI can significantly reduce NIHSS scores,and improve Barthel index and overall effective rate.The efficacy is better than edaravone alone,and a more comprehensive evaluation of safety is needed in the future.