Objective To mine and analyze adverse drug events(ADEs)of novel agents for multi-drug-resistant tuberculosis(MDR-TB)based on the FDA Adverse Event Reporting System(FAERS)database,to explore the signals of ADEs,and to provide reference for clinical use.Methods The FAERS database was searched and extracted from Q1 of 2015 to Q4 of 2023,and the ADE reports about bedaquiline,delamanid,and pretomanid were collected.Data mining and analysis were carried out on relevant reports of the drug using the reporting odds ratio(ROR),proportional reporting ratio(PRR),medicines and healthcare products regulatory agency(MHRA),and the Bayesian confidence progressive neural network(BCPNN).Results The number of ADE reports for the target drugs bedaquiline,delamanid,and pretomanid were 2 477,1 630,and 173,respectively.ADE of the target drugs involved multiple organ systems.Positive signals detected by the ROR,PRR,MHRA,and BCPNN methods were 246,246,215,204 for bedaquiline;251,251,224,200 for delamanid;and 25,25,24,22 for pretomanid.Clinically significant high-risk signals include prolonged QT interval on ECG,anemia,liver toxicity,peripheral neuropathy,etc.Conclusions The signal mining of ADEs based on the FAERS database indicates that close attention should be paid to risks such as prolonged QT interval on ECG,anemia,liver toxicity,and peripheral neuropathy during the clinical use of bedaquiline,delamanid,and pretomanid.In addition,monitoring of new potential ADE signals(such as acute heart failure,respiratory failure,acute kidney injury,etc.)should be strengthened,and timely intervention measures should be taken to ensure medication safety.

ObjectiveTo investigate whether co-activated mesenchymal stem cells（MSCs） exert therapeutic effects against schistosomiasis by modulating macrophage polarization. MethodsTwenty adult male Balb/c mice were randomly divided into four groups： uninfected， infected， MSC-treated， and MSC^TLR4+IFN-γ-treated groups. The Schistosoma japonicum infection model was established via abdominal patch method with cercariae. At week 5 post-infection， praziquantel was administered orally for antiparasitic treatment. At week 6， mice received either MSCs treatments （with or without pre-activation） or no treatment. Body weight changes were monitored weekly. Hepatic pathological alterations were evaluated via HE and Masson staining. RT-qPCR was used to assess α-SMA and collagen （Col-I， Col-Ⅲ） mRNA levels to quantify fibrosis. The mRNA levels of hepatic inflammatory cytokines and matrix metalloproteinases（MMP） were analyzed to explore fibrotic mechanisms. The expressions of i-Nos and Arg-1 in liver tissues were detected by RT-qPCR， and the ratio of M1 or M2 macrophages was detected by immunofluorescence staining， aiming to analyze the correlation between MSCs treatment and macrophage polarization. An in vitro co-culture system validated direct MSC-macrophage interactions. ResultsCompared with the infected group， the MSC^TLR4+IFN-γ group exhibited increased body weight gain （P< 0.01）， reduced hepatic granulomatous lesion area （P< 0.001）， and decreased α-SMA， Col-I， and Col-Ⅲ mRNA levels （P< 0.01）. Additionally， the MSC^TLR4+IFN-γ group showed reduced TNF-α and IL-1β expression （P< 0.05）， as well as elevated MMP2， Mmp9， and MMP13 levels （P< 0.01）. The MSC^TLR4+IFN-γ group showed higher expression of M2 marker Arg-1 mRNA compared with the infection group （P < 0.001） ， while the expression of M1 marker i-Nos decreased （P< 0.05）. Immunofluorescence confirmed a lower i-Nos+ cell ratio （P< 0.05） and higher F4/80⁺CD206⁺ cell ratio （P< 0.000 1） in the MSC^TLR4+IFN-γ group compared with the infection group. In vitro co-culture experiments further demonstrated that MSC^TLR4+IFN-γ promoted Arg-1 expression， suppressed pro-inflammatory cytokine i-Nos and TNF-α levels， consistent with ELISA results. ConclusionsThis study reveals that TLR4 and IFN-γ co-activated MSCs alleviate Schistosoma japonicum-induced hepatic fibrosis， potentially through modulating macrophage polarization toward the M2 phenotype. This mechanism may suppress inflammation and enhance extracellular matrix degradation， providing a therapeutic strategy for schistosomiasis-associated liver fibrosis.

The theory of " Sui Qi Suo De" originates from Zhang Zhongjing's Jin Gui Yao Lue and has been further developed by later generations of practitioners, offering significant guidance for clinical practice. Myelodysplastic syndromes (MDS) are common malignant disorders of the hematopoietic system, characterized by high heterogeneity and progressive mutational changes. In Traditional Chinese Medicine (TCM), MDS falls under the category of "marrow toxin exhaustion". This article applies the theory of " Sui Qi Suo De" in TCM to analyze the pathophysiological changes during different stages of MDS. Specifically, it explores the precursor stage (focusing on health maintenance and prevention before illness, addressing the " Suo De" of "gradual decline of vital qi"), the low-risk stage (strengthening the spleen and kidneys, clearing toxic pathogens, addressing the " Suo De" of "weakened vital qi invaded by pathogens"), and the medium-to-high-risk stage (detoxifying and reinforcing the body, harmonizing physical and mental health, addressing the " Suo De" of "dominant pathogens and declining vital qi"). The goal is to provide new directions and theoretical insights for the TCM treatment of MDS.

Objective:To investigate the clinical efficacy of autologous adipose-derived stem cell gel (SVF-gel) grafting in the treatment of depressed acne scars.Methods:A retrospective analysis was conducted on data collected from 28 patients who underwent SVF-gel grafting treatment for depressed acne scars in the Department of Dermatology, Xijing Hospital, Air Force Medical University from October 2018 to May 2021. There were 17 males and 11 females, aged 17 - 38 (26 ± 4.86) years. As for clinical types, 8 patients were diagnosed with boxcar acne scars, 14 with rolling acne scars, and 6 with acne scars with characteristics of the two types. The clinical acne scar weighted scale (ECCA scale) was used to evaluate the appearance improvement after the treatment, and patients′ subjective satisfaction scores and incidence of adverse reactions were recorded.Results:After the SVF-gel grafting, the facial appearance of patients with depressed acne scars significantly improved, and the ECCA scores significantly decreased 6 months after surgery (before surgery: 52.5 ± 15.8 points; 6 months after surgery: 23.8 ± 10.2 points; t = 11.68, P < 0.001). The subjective satisfaction rate of patients was 82.14% (23/28), the incidence rate of adverse reactions was 17.86% (5/28), and 5 patients experienced mild inflammatory reactions after surgery, including 2 with subcutaneous nodules. The secondary grafting rate was 67.86% (19/28) . Conclusion:The SVF-gel grafting was markedly effective for the treatment of depressed acne scars, which is worthy of clinical promotion and application.

[This corrects the article DOI: 10.1016/j.apsb.2021.07.004.].

This study aims to simultaneously detect three antibiotic resistance genes(blaNDM,mcr-1 and cfr).A triplex fluorescence quantitative PCR method was established.Plasmids,primers and probes were designed and optimized.The method could specifically detect blaNDM,mcr-1 and cfr,but not other antibiotic resistance genes.The R2 of the standard curves of the three antibiotic re-sistance genes were all greater than 0.999,and the coefficients of variation were all lower than 1％.The lowest detection limits of the plasmids were 1 × 102 copies/μL.This method was used to de-tect 800 bacterial samples.The results showed that 32 samples contained mcr-1 gene,40 samples contained blaNDM gene,2 samples contained cfr gene,8 samples contained both mcr-1 and blaNDM genes.There were no samples carrying three antibiotic resistance genes detected.The results indica-ted that the triplex fluorescence quantitative PCR method established in this experiment had the advantages of high sensitivity,specificity and stability.It was suitable for rapid detection of blaNDM,mcr-1 and cfr antibiotic resistance genes in clinical practice.It provided a convenient and quick method basis for the detection of antibiotic resistance genes.

Objective:To investigate the clinical efficacy of autologous adipose-derived stem cell gel (SVF-gel) grafting in the treatment of depressed acne scars.Methods:A retrospective analysis was conducted on data collected from 28 patients who underwent SVF-gel grafting treatment for depressed acne scars in the Department of Dermatology, Xijing Hospital, Air Force Medical University from October 2018 to May 2021. There were 17 males and 11 females, aged 17 - 38 (26 ± 4.86) years. As for clinical types, 8 patients were diagnosed with boxcar acne scars, 14 with rolling acne scars, and 6 with acne scars with characteristics of the two types. The clinical acne scar weighted scale (ECCA scale) was used to evaluate the appearance improvement after the treatment, and patients′ subjective satisfaction scores and incidence of adverse reactions were recorded.Results:After the SVF-gel grafting, the facial appearance of patients with depressed acne scars significantly improved, and the ECCA scores significantly decreased 6 months after surgery (before surgery: 52.5 ± 15.8 points; 6 months after surgery: 23.8 ± 10.2 points; t = 11.68, P < 0.001). The subjective satisfaction rate of patients was 82.14% (23/28), the incidence rate of adverse reactions was 17.86% (5/28), and 5 patients experienced mild inflammatory reactions after surgery, including 2 with subcutaneous nodules. The secondary grafting rate was 67.86% (19/28) . Conclusion:The SVF-gel grafting was markedly effective for the treatment of depressed acne scars, which is worthy of clinical promotion and application.

Objective To mine and analyze adverse drug events(ADEs)of novel agents for multi-drug-resistant tuberculosis(MDR-TB)based on the FDA Adverse Event Reporting System(FAERS)database,to explore the signals of ADEs,and to provide reference for clinical use.Methods The FAERS database was searched and extracted from Q1 of 2015 to Q4 of 2023,and the ADE reports about bedaquiline,delamanid,and pretomanid were collected.Data mining and analysis were carried out on relevant reports of the drug using the reporting odds ratio(ROR),proportional reporting ratio(PRR),medicines and healthcare products regulatory agency(MHRA),and the Bayesian confidence progressive neural network(BCPNN).Results The number of ADE reports for the target drugs bedaquiline,delamanid,and pretomanid were 2 477,1 630,and 173,respectively.ADE of the target drugs involved multiple organ systems.Positive signals detected by the ROR,PRR,MHRA,and BCPNN methods were 246,246,215,204 for bedaquiline;251,251,224,200 for delamanid;and 25,25,24,22 for pretomanid.Clinically significant high-risk signals include prolonged QT interval on ECG,anemia,liver toxicity,peripheral neuropathy,etc.Conclusions The signal mining of ADEs based on the FAERS database indicates that close attention should be paid to risks such as prolonged QT interval on ECG,anemia,liver toxicity,and peripheral neuropathy during the clinical use of bedaquiline,delamanid,and pretomanid.In addition,monitoring of new potential ADE signals(such as acute heart failure,respiratory failure,acute kidney injury,etc.)should be strengthened,and timely intervention measures should be taken to ensure medication safety.

This study aims to simultaneously detect three antibiotic resistance genes(blaNDM,mcr-1 and cfr).A triplex fluorescence quantitative PCR method was established.Plasmids,primers and probes were designed and optimized.The method could specifically detect blaNDM,mcr-1 and cfr,but not other antibiotic resistance genes.The R2 of the standard curves of the three antibiotic re-sistance genes were all greater than 0.999,and the coefficients of variation were all lower than 1％.The lowest detection limits of the plasmids were 1 × 102 copies/μL.This method was used to de-tect 800 bacterial samples.The results showed that 32 samples contained mcr-1 gene,40 samples contained blaNDM gene,2 samples contained cfr gene,8 samples contained both mcr-1 and blaNDM genes.There were no samples carrying three antibiotic resistance genes detected.The results indica-ted that the triplex fluorescence quantitative PCR method established in this experiment had the advantages of high sensitivity,specificity and stability.It was suitable for rapid detection of blaNDM,mcr-1 and cfr antibiotic resistance genes in clinical practice.It provided a convenient and quick method basis for the detection of antibiotic resistance genes.

Objective:To investigate the clinical and genetic characteristics of developmental and epileptic encephalopathy (DEE) caused by SLC1A2 gene mutations. Methods:The clinical manifestations, auxiliary examination results, and genetic testing results of a patient with DEE caused by SLC1A2 gene mutations who was treated at Epilepsy Center, Children's Hospital Affiliated to Shandong University on February 6, 2021 were summarized. Cases of SLC1A2 gene mutations were searched using keywords " SLC1A2" and "developmental and epileptic encephalopathy" in CNKI, Wanfang, and PubMed databases, retrieving literature published from the establishment of these databases to September 2024. Bioinformatics analysis was performed; the clinical and genetic characteristics of DEE caused by SLC1A2 gene mutations were summarized. Results:The main manifestations of the patient were rhythmic shaking of the right upper limb or focal motor seizures of bilateral upper limbs, or focal spasm of right upper limb (elevation for once). Ictal electroencephalogram showed 2-3 Hz polymorphic slow waves in the left central area, parietal area and central midline area, affecting the opposite side, or spike rhythm with decreased frequency in the right frontal area, central area and midline area, or polymorphic slow waves in the left central area and central midline area. Whole-exome sequencing indicated a heterozygous de novo mutation in the SLC1A2 gene: c.254T>G/p.Leu85Arg. A total of 7 patients with DEE caused by SLC1A2 gene mutations were retrieved from 5 related literature. All 8 patients (including the patient in our hospital) presented with epileptic seizure, developmental delay, and abnormal EEG; all of them were sporadic cases with de novo heterozygous missense mutations of SLC1A2 gene. Bioinformatics analysis showed that the 4 amino acid residues Gly82, Leu85, Pro289, and Pro333 in the 8 patients were located in the intolerance region of SLC1A2 gene encoding glutamate transporter protein 2 (EAAT2). The 5 amino acid mutations (Leu85Arg, Leu85Pro, Gly82Arg, Pro333Ser, Pro289Arg) in the 8 patients all led to significant changes in number and binding of hydrogen bonds between amino acid residues in EAAT2; except for Gly82Arg mutation, the other 4 mutations could obviously reduce the structural stability of EAAT2. Conclusion:De novo heterozygous missense mutations in SLC1A2 gene can lead to DEE, characterized by developmental delay, EEG abnormalities, and epileptic seizure; these mutations are typically located in critical regions of EAAT2, potentially resulting in reduced protein structural stability.