Objective : To investigate the mechanisms of bromodomain-containing protein 4(BRD4) in TGF-β1-induced epithelial-mesenchymal transition in alveolar type II epithelial cells. Methods : MLE-12 cells were stimulated with different concentrations(5 ng/ml, 10 ng/ml) of TGF-β1 for 48 h to establish an EMT cell model. The cells were pretreated with 50 nmol/L BRD4 inhibitor JQ-1, 100 μmol/L high mobility group box 1 protein(HMGB1)inhibitor glycyrrhizin acid(GA), and 3 μg/ml rHMGB1. The experimental groups were divided as follows: control group, TGF-β1 group, JQ-1 group, JQ-1+TGF-β1 group, GA group, GA+TGF-β1 group, and JQ-1+TGF-β1+rHMGB1 group. The effect of JQ-1 on cell viability was examined using cell counting kit-8(CCK-8). The protein expression levels of CDH1, ZO-1, Vimentin, α-SMA, BRD4, HMGB1, TGF-β1, Smad2/3 and p-Smad2/3 were detected by Western blot. The cell migration ability was detected by a scratch test. Results : Compared with the control group, the levels of Vimentin and α-SMA in the TGF-β1 group increased, and the levels of CDH1 and ZO-1 protein decreased, suggesting that the EMT model was successfully established. In this model, the expression of BRD4 and HMGB1 significantly increased. Different concentrations of JQ-1 could inhibit the cell viability of MLE-12 in a concentration-dependent manner. Both JQ-1 and GA could effectively alleviate TGF-β1-induced EMT, and reduce the increase in HMGB1 expression and the activation of TGF-β1/Smad2/3 pathway caused by TGF-β1. Moreover, rHMGB1 treatment could reduce the effects of JQ-1 on EMT and the TGF-β1/Smad2/3 pathway. Additionally, both JQ-1 and glycyrrhizin could effectively decrease TGF-β1-induced cell migration, whereas rHMGB1 could alleviate the inhibitory effect of JQ-1 on the rate of cell migration. Conclusion BRD4 can regulate epithelial-mesenchymal transition in alveolar type II epithelial cells via HMGB1/TGF-β1/Smad2/3 signaling cascade, and BRD4 may be a potential target for inhibition of pulmonary fibrosis.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

In the context of"Artificial Intelligence(AI)+Education"era,this study introduces the teaching reform and devel-opment path of the course"Fundamentals of Immunology and Pathogenic Biology"by Professor Lu Fangguo's team at Hunan University of Traditional Chinese Medicine.After twenty years of exploration,the course has successfully transitioned from traditional teaching to intelligent teaching,achieving a comprehensive upgrade in educational concepts,teaching methods,and resources.The reform process is divided into three stages:Early exploration,comprehensive reform,and deepening development.It encompasses the construction of a smart teaching platform,the development and promotion of new forms of digital teaching resources,and the deep integration of ideological and political education.This reform has significantly enhanced teaching quality and students'overall competencies,showcasing the innovative spirit of educators.It has gained nationwide recognition and promotion,providing valuable references for the innovation of medical education in the new era.

Cultural confidence is an important part of nurturing"confidence in the path,theory,system,and culture of social-ism with Chinese characteristics"students,as well as the important direction of ideological and political courses,and play an impor-tant role for establishing the core values of Chinese socialism.This paper summarized the reform exploration and practical experience of the Basic Immunology and Pathogen Biology through deeply excavating the core ideas of Chinese medicine culture based on the course content for improving the cultural confidence.The object of this paper is to improving the effectiveness of education.

Objective:To construct a meridian tapping exercise program for frail elderly, so as to provide daily healthcare options for frail elderly people.Methods:Guided by the theory of meridians and collaterals, data mining was conducted on the database of ancient Chinese medical literature to select acupoints and meridians for tapping. Through literature research, the exercise prescription was improved. A preliminary exercise prescription was formulated through literature review and revised through two rounds of expert consultation in December 2023.Results:The effective response rate for both rounds of expert consultation questionnaires was 7/7. The expert authority coefficients were 0.83 and 0.87, respectively, and the overall Kendall′s coefficient of concordance was 0.301 and 0.302 (both P<0.05). The final meridian tapping exercise for frail elderly comprised 2 primary indicators, 8 secondary indicators, and 23 tertiary indicators. Conclusions:The meridian tapping exercise for the frail elderly is scientific, reliable and practical, which can provide a choice for the frail elderly to carry out targeted traditional Chinese medicine exercises.

Objective:To investigate the characteristics of RET gene rearrangement revealed by fluorescence in situ hybridization (FISH) in lung cancer.Methods:A total of 616 formalin-fixed paraffin-embedded surgical samples from lung adenocarcinomas with wild-type EGFR gene and no ALK protein expression by immunohistochemistry obtained at Peking Union Medical College Hospital, Beijing, China between December 2019 and April 2022 were included. Thirty-three tumors with RET gene rearrangement determined by imbalanced-based reverse-transcription droplet digital PCR (RT-ddPCR) were analyzed using break-apart FISH. The results were confirmed, and RET gene fusion variants were identified through next generation sequencing (NGS).Results:RET gene rearrangements were found in all 33 RET RT-ddPCR positive cases via NGS, including 27 cases of KIF5B::RET, 3 CCDC6::RET, 2 ERC1::RET and 1 CCDC186::RET rearrangements. Moreover, 32 RET positive and 1 RET negative cases were defined using FISH. Among the RET FISH-positive cases, 25 (78.1%, 25/32) showed break-apart FISH signal pattern in 52%-100% of tumor cells with the rearrangement and 7 cases (21.9%, 7/32) presented isolated 3′ signal type in 38%-88% positive tumor cells. There was no RET-positive case with single 5′ pattern in the cohort. The most common partner gene was KIF5B (81.8%, 27/33). Most of the patients with RET gene rearrangement were female (72.7%, 24/33).Conclusion:RET FISH-positive lung cancer is commonly characterized by a high proportion of rearrangement cancer cells and break-apart FISH signal type.

Objective:To establish a fluorescent quantitative RT-PCR assay based on N_sgRNA of SARS-CoV-2 and preliminarily apply it on real samples.Methods:Recombinant plasmid, specific primers and probes of N_sgRNA were designed and synthesized based on Wuhan-Hu-1/2019_MN908947 and synthesis mechanism of subgenomic RNA (sgRNA). Using recombinant plasmid as amplification templates, the optimal reaction conditions and reaction system were screened according to the Ct value, fluorescence intensity, and shape of amplification curve and was evaluated for sensitivity, reproducibility, and specificity. Meanwhile, the possibility of practical application of the method was explored by testing 172 clinical samples and 256 municipal wastewater samples. Results:A qRT-PCR assay for N_sgRNA in SARS-CoV-2 was initially established. The detection limit of the assay was 20 copies/mL, and the variation coefficients of in-batch (0.002%~0.767%) and batch to batch repetition (0.016%~0.752%) were less than 1%. Only N_sgRNA recombinant plasmid was detected in the specificity assay. So the method is more highly sensitive, specific and reproducible. The RatiosgRNA/ gRNA of clinical samples HK.3, EG.5.1, JN.1 and their sub-lineages and their corresponding urban sewage samples in epidemic period were significantly different ( P<0.05). There is a strong correlation between the median of RatiosgRNA/ gRNA in clinical samples and sewage samples in the same period (correlation coefficient r=1.000, P=0.010). Conclusions:In this study, a qRT-PCR method for detecting N_sgRNA of SARS-CoV-2 was established and the method has the characteristics of higher sensitivity, stronger specificity and better repeatability, and it can be used to detect SARS-CoV-2 infectivity.

The sterile electrode acupuncture needle for single use is an innovative product that combines traditional acupuncture with modern electronic technology, and it has obtained Class Ⅱ medical device registration certificate. This acupuncture device consists of a needle body and a handle. The diameter of the needle body ranges from 0.16 mm to 0.55 mm, and the length from 7 mm to 150 mm. The spiral spray technology is adopted to modify the micron-level insulating coat on stainless steel needle body. The needle holder is connected to the electroacupuncture device (conductive), the micro-film insulated needle body (non-conductive) and the membrane-free needle tip (conductive) can provide a precise electrical stimulation for different tissue layers of acupoints (such as deep nerves and fascia). The intradermal stimulation test, cytotoxicity test and hypersensitivity reaction test have showed a favorable biocompatibility, laying a solid and reliable safety for clinical application. This acupuncture device is suitable for the in-depth invasive stimulation at the sites of human body surface in combination with electroacupuncture equipment in medical institutions.
Humans ; Needles ; Acupuncture Therapy/instrumentation* ; Electrodes ; Equipment Design ; Electroacupuncture/instrumentation* ; Acupuncture Points ; Animals

Objective:To summarize the technical difficulties, key points and cosmetic effects of Ti-loop patch application in breast shaping of immediate reconstruction with omental flap transplantation after mastectomy.Methods:The clinical data of 90 cases with breast cancer who underwent immediate breast reconstruction by using laparoscopically harvested omental flap alone or combined with prosthesis after nipple and areola complex sparing mastectomy from May. 2020 to Jan. 2023 in Hunan Cancer Hospital was retrospectively analyzed. All patients were female between 16 and 55 years old with the average age of 42. Their courses of the disease range from 5 to 26 months with the mean of 15.5 months. These patients received mastectomy with conservation of nipple and areola, and then the greater omentum with right pedicle were harvested laparoscopically. Ti-loop patch was used to hang and fix the greater omentum as a support. 27 patients accepted immediate breast reconstruction with pedicled greater omentum alone, while 63 subjects with greater omentum and gel prosthesis. Among them, contralateral breast contraction and lift was operated on 9 cases.Results:All the pedicled greater omentum successfully survived, and wound surfaces of donor and recipient sites healed at stage I. Axillary lymph node dissection and postoperative radiotherapy were performed on 14 patients with positive pathological examination of sentinel lymph nodes. Breasts of two patients were found to be smaller after postoperative radiotherapy. All 90 subjects were followed up for 5 to 32 months, and the average follow-up period was 16.4 months. The reconstructed breasts were good in shape and tactile sensation. Only punctate scars were observed in donor sites of abdomen. All patients recovered with no upper limb lymphedema, no short and long term complications in abdomen, and only one patient had papillary recurrence without distant metastasis.Conclusions:The omental flap is hard to be sutured and shaped in the reconstructed breast, while easily to be avulsed and form hematoma. The application of Ti-loop patch, which could semi-surround and wrap the greater omentum, and suspend and fix it on the chest wall in upper pole of the breast as a support, can significantly improve the reconstruction effect.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.