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

Objective:To investigate the effects of external application of Sanying Plaster on the size of thyroid nodules and the states of depression and anxiety in patients with benign thyroid nodules.Methods:A randomized controlled trial was conducted. A total of 120 patients with benign thyroid nodules from the outpatient clinic of the Department of Thyroid Diseases at Shanghai Traditional Chinese Medicine Hospital from June to December 2022 were selected as the subjects of the study. They were divided into two groups using the random number table method, with 60 patients in each group. The control group received lifestyle intervention treatment, while the treatment group received Sanying Ointment in addition to the treatment of the control group. Both groups were treated for 3 months. TCM syndrome scores were measured before and after treatment; the maximum diameter of thyroid nodules was measured using a color Doppler ultrasound transverse section; the quality of life was assessed using the short form 36 (SF-36); the degree of anxiety and depression was evaluated using the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS); adverse reactions during the treatment period were recorded, and the clinical efficacy was evaluated.Results:During the treatment period, 4 cases in the treatment group and 3 cases in the control group did not complete the treatment. Finally, 56 cases in the treatment group and 57 cases in the control group entered the efficacy evaluation. The total effective rate of the treatment group was 71.4% (40/56), and that of the control group was 14.0% (8/57), with a statistically significant difference between the two groups ( χ2=26.82, P<0.001). After treatment, the TCM syndrome score of the treatment group (10.02±3.65 vs. 16.65±3.44, t=-10.24) was lower than that of the control group ( P<0.001); the maximum diameter of thyroid nodules [11.00 (4.65, 19.93) mm vs. 15.00 (7.15, 28.50) mm, Z=-2.43] was lower than that of the control group ( P<0.05); the SF-36 score [121.83 (117.00, 130.00) vs. 114.42 (104.25, 127.50), Z=-2.62] was higher than that of the control group ( P<0.01); the SDS (46.72±4.59 vs. 57.02±5.99, t=14.80) and SAS (42.25±5.72 vs. 50.60±7.12, t=10.04) scores were lower than those in the control group ( P<0.001). The incidence of adverse reactions during the treatment period in the treatment group was 3.5% (2/57), and no adverse reactions occurred in the control group. Conclusion:The external application of Sanying Ointment helps to reduce the size of thyroid nodules in patients with benign thyroid nodules, improve the quality of life and anxiety and depression, and increase clinical efficacy with good safety.

Objective To analyze the current status and hotspots of surgical transmural ablation of atrial fibrillation using CiteSpace and VOSviewer. Methods The Web of Science Core Collection database was used as the data source. The CiteSpace 5.8.R3 and VOSviewer software were used to analyze the related studies on surgical transmural ablation of atrial fibrillation about the authors, countries/institutions, literature co-citation and keywords. Results A total of 109 articles were enrolled. Damiano RJ was the most prolific researcher, while Cox JL was the author with the highest number of citations. The United States was the leading country in this research field. The University of Washington was an important institution in the study of atrial fibrillation transmural ablation. The main hotpots were the effectiveness of surgical ablation, especially Cox-maze procedure, selection of the energy source of surgical ablation, combination of surgical and catheter ablations, and pulmonary vein isolation. Conclusion This study visualizes the current research status of surgical ablation of atrial fibrillation. How to improve the effectiveness and transmurality of surgical ablation is a hot research topic in the surgical treatment of atrial fibrillation. The combination of electrophysiology mapping and surgical ablation may be the development direction in the surgical treatment of atrial fibrillation.

Objective:To determine the expression of adenylate cyclase genes ADCY2/4/5/8 in cutaneous melanoma, to explore their roles and mechanisms of action, and to verify their effect on the proliferation and migration of the melanoma cell line A375.Methods:Data on the mRNA and protein expression of ADCY2/4/5/8, as well as the correlation between gene expression and prognosis, were analyzed through the Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases; ADCY2/4/5/8 gene methylation and mutation status were analyzed through the UALCAN, DeMth, and cBioPortal databases; Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed on the ADCY2/4/5/8 genes using the DAVID and STRING databases. qPCR was conducted to determine the relative mRNA expression of ADCY2/4/5/8 in the A375 melanoma cells and FF pigmented nevus cells. Cultured A375 cells were divided into experimental groups and control groups to be transfected with ADCY2/4/5/8 overexpression plasmids and empty vectors, respectively. Cell counting kit (CCK8) and Transwell assays were performed to evaluate the effect of ADCY2/4/5/8 overexpression on the proliferation and migration of A375 cells, qPCR was conducted to determine the relative mRNA expression of genes related to the proliferation and migration of A375 cells, and Western blot analysis to determine the expression of cyclic adenosine monophosphate (cAMP) signaling pathway-related proteins in A375 cells after the overexpression of ADCY2/4/5/8. One-way analysis of variance and repeated measures analysis of variance were used for the comparison among multiple groups, and least significant difference- t test was used for multiple comparisons. Results:Bioinformatics analysis based on the GEPIA database showed that the mRNA expression of ADCY2, ADCY4, ADCY5, and ADCY8 was down-regulated in melanoma tissues ( n = 461) compared with normal tissues ( n = 558, P < 0.01) ; stratified analysis showed that the mRNA expression of ADCY2 ( P = 0.015) and ADCY8 ( P = 0.038) was correlated with tumor staging, and the lower the mRNA expression, the later the tumor stage. In the HPA database, the ADCY2/4/5/8 protein expression was reduced in 30 melanoma tissues compared with 30 normal tissues ( P < 0.001). Analysis of the UALCAN and DeMth database data showed elevated methylation levels of ADCY2/4/5/8 in melanoma tissues and metastatic melanoma tissues compared with normal tissues ( P < 0.001). Analysis of the DAVID and STRING database data demonstrated that the ADCY2/4/5/8 gene may inhibit cell proliferation and migration by activating the cAMP signaling pathway. qPCR showed that the relative mRNA expression of ADCY2/4/5/8 was lower in A375 cells than in FF cells. CCK8 assay showed that the survival rates of A375 cells were significantly lower in the ADCY2/4/5/8 overexpression groups than in the corresponding control groups at 48 and 72 hours (all P < 0.05). Transwell assay showed that the number of migratory A375 cells was significantly lower in the ADCY2/4/5/8 overexpression groups than in the corresponding control groups (all P < 0.01). As qPCR revealed, the ADCY2/4/5/8 overexpression groups showed significantly upregulated relative mRNA expression of epithelial cadherin, but significantly downregulated relative mRNA expression of Ki67, vimentin, neural cadherin, and matrix metalloproteinase 2 compared with the corresponding control groups (all P < 0.001). Western blot analysis showed that the protein expression of cAMP and phosphorylated protein kinase A (p-PKA) in A375 cells was significantly higher in the ADCY2/4/5/8 overexpression groups than in the corresponding control groups (all P < 0.001), but there were no significant differences in the PKA protein expression levels between the ADCY2/4/5/8 overexpression groups and the corresponding control groups (all P > 0.05) . Conclusion:The expression of ADCY2/4/5/8 was downregulated in melanoma tissues, and overexpressed ADCY2/4/5/8 could inhibit the proliferation and migration of melanoma cells, suggesting that ADCY2/4/5/8 may serve as potential tumor suppressor genes in the progression of melanoma.

Objective To explore the expression levels and clinical significance of basement membrane genes in endometrial carcinoma and the prognostic value of a prediction model.Methods The mRNA expression matrix and clinical data for endometrial carcinoma were obtained from The Cancer Genome Atlas(TCGA)database,and basement membrane genes were obtained from a previous study.Prognostic genes were screened using univariate and multivariate Cox regression analyses based on differentially expressed genes(DEGs).A prognostic model was constructed,and the relationship of these genes with clinical factors was analyzed.The biological functions and pathways of the DEGs were assessed using functional enrichment analyses.The mRNA expression of prognostic genes was verified using real-time polymerase chain reaction(PCR).Results The prognostic model composed of ACHE,COL12A1,and CD44was significantly associated with clinical factors.Real-time PCR results showed that the expression levels of ACHEand COL12A1mRNA differed signifi-cantly between normal endometrial cells and endometrial carcinoma cells(P<0.05).Conclusion The constructed model based on three basement membrane genes can accurately predict the prognosis of patients with endometrial carcinoma and provide potential targets for clinical treatment.

In recent years, the corona virus disease 2019 (COVID-19) pandemic has had a huge impact on the global medical, political and economic fields. Since the beginning of the COVID-19 epidemic, our understanding of the impact of COVID-19 has grown exponentially. Recently, the COVID-19 epidemic has changed rapidly in China, and there has been controversy over how to carry out surgical operations for patients with lung neoplastic lesions. Some studies have shown that lung cancer patients undergoing surgery are more likely to experience respiratory failure and perioperative death after contracting COVID-19 than the general population, however, delays in cancer treatment are also associated with increased mortality among these patients. In particular, the novel coronavirus Omikron variant has a higher transmissibility and may escape the immunity obtained through the previous novel coronavirus infection and vaccination. In order to minimize the risk of novel coronavirus infection in surgical patients, it is necessary to develop new treatment guidelines, expert consensus and preventive measures. However, the current rapid change of the epidemic situation has led to insufficient time and evidence to develop guidelines and consensus. Therefore, thoracic surgeons need to evaluate specific patient populations at higher risk of severe complications before surgery and weigh the benefit of surgical treatment against the risk of novel coronavirus infection. We try to give some recommendations on lung surgery during the current domestic epidemic situation based on the guidelines and consensus of oncology and thoracic surgery organizations in different regions on lung surgery.
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Humans ; Lung Neoplasms/complications* ; COVID-19 ; SARS-CoV-2 ; Multiple Pulmonary Nodules ; Pandemics/prevention & control* ; Lung

Objective:To investigate the expression, methylation and prognosis of DKK2 in non-small cell lung cancer, and also its effect and correlation with the sensitivity of hypofractionated radiotherapy sensitivity in non-small cell lung cancer.Methods:qPCR, online database and Kaplan-Meier survival curve were used to detect the expression, methylation and prognosis of DKK2 in NSCLC samples. A549 cells was set as the research objects, and cloning formation experiment and Western blot were used to evaluated the effects of DKK2 on hypofractionated radiotherapy in NSCLC.Results:Compared with the normal tissues, the expression of DKK2 mRNA in NSCLC samples was down-regulaged [ (0.00042±0.0001) vs (0.00065±0.0002), P<0.001]. Data taken from an online methylation database showed that compared with normal tissue, DKK2 hypermethylated in NSCLC, and its methylation was significantly negatively correlated with the mRNA expression. Downregulated DKK2 expression was inversely correlated with its methylation status ( P=0.034). The hypofractionated radiotherapy sensitivity of NSCLC patients was 53.3%. Compared with radiosensitivity group, DKK2 mRNA expression was significantly down-regulated in radioresistance group[ (0.00064±0.0002) vs (0.00043±0.0002), P<0.001]. The progression free survival of radiotherapy sensitive group was better than that of radiotherapy resistant group (median PFS: 21.4 months vs 4.6 months). Ectopic expression of DKK2 in A549 lines inhibited colony formation after irradiation with 4 Gy X-ray radiotherapy. Western blot further showed that restoration of DKK2 expression resulted in upregulation of DNA damage markers γ-H2AX[ (1.00±0.24) vs (3.22±0.41), P<0.001], and the difference was statistically significant. Conclusion:DKK2 expression is downregulated in NSCLC due to methylation, which may be acted as an important target to predict the hypofractionated radiotherapy sensitivity of NSCLC.

OBJECTIVE To investigate the effect and mechanism of α7 nicotinic acetylcholine receptor （α7nAChR） agonists PNU-282987 on cognitive function in temporal lobe epilepsy （TLE） model rats. METHODS Sixty rats were randomly divided into control group， model group， PNU-282987 group （3 mg/kg） and methyllycaconitine （MLA）+PNU-282987 group （6 mg/kg MLA+3 mg/kg PNU-282987）， with 15 rats in each group. Except for control group， the TLE model was established in the other groups. After the model was successfully established， each group was given relevant medicine or normal saline intraperitoneally， once a day， for two consecutive weeks. The epilepsy attack of rats was observed and scored， and the duration of seizures was recorded； the cognitive function of rats was detected； pathological morphology of neurons in CA1 region was observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in the hippocampus were detected； the positive expressions of ionized calcium-binding adapter molecule-1 （IBA-1）， α7nAChR， nuclear factor-κB （NF-κB） p65， p-NF-κB p65 in the hippocampus were detected. RESULTS Compared with model group， the score and duration of seizures， the number of IBA-1 positive cells， the levels of TNF- α， IL-6 and IL-1β， the expressions of NF- κB p65 and p-NF- κB p65 protein decreased significantly in the hippocampus （P＜0.05）； the escape latency time was shortened significantly （P＜0.05）， the time spent in the original platform quadrant and times of crossing the platform increased significantly （P＜0.05）； neuronal damage in the CA1 region of the hippocampus was significantly reduced； the expression of α7nAChR protein increased significantly in hippocampus （P＜0.05）. Compared with PNU-282987 group， the above indexes of rats in MLA+PNU-282987 group were reversed significantly （P＜0.05）. CONCLUSIONS PNU-282987 could improve cognitive dysfunction in TLE model rats， and its mechanism may be associated with inhibiting microglia-mediated inflammatory response through α7nAChR/NF- κB signaling pathway， thus reducing hippocampal neuronal damage.

Objective:To investigate the anatomy of lateral maxillocervical boot-shaped perforator fasciocutaneous flap and its clinical effect on repairing soft tissue defect of zygomatic-temporal region.Methods:(1)From December 2017 to December 2020, five fresh adult cadaver specimens were infused with gelatin lead oxidate and underwent one-time arteriography.The X-ray image was imported into Mimics 17.0 software, divided and colored based on the head and face anatomy, and the distribution and anastomosis of the arteries involved in the lateral maxillocervical boot-shaped perforator fasciocutaneous flap were observed.The head and neck samples of another 5 (10 sides) fresh adult cadavers were infused with red latex artery to establish the surgical model, and then dissected layer by layer to investigate the blood supply and the source of perforating artery of this flap.(2) The patients with zygomatic-temporal lesions were treated in the Department of Plastic Surgery, the First Affiliated Hospital of Anhui Medical University.They were treated with the lateral maxillocervical boot-shaped perforator fasciocutaneous flap to repair the wound left after lesion resection. The survival of the flap and the healing of the incision were observed after surgery and the appearance and sensation of donor and recipient sites as well as tumor recurrence were followed up.Results:(1) The pedicle of the lateral maxillocervical boot-shaped perforator fasciocutaneous flap is mainly nourished by the superficial temporal artery and its perforator.The average diameter of the maximum three perforations is (0.44±0.04) mm, (0.90±0.08) mm, (0.73±0.05) mm.The fascial vascular network and subdermal vascular network formed by perforating arteries from superficial temporal artery and branching arteries from facial artery at different layers are the anatomical basis for ensuring blood supply of lateral maxillocervical boot-shaped perforator fasciocutaneous flap. (2) A total of 12 patients with zygomatic-temporal lesions were treated clinically, including 8 males and 4 females aged 42-79 years, including 2 cases of senile sebaceous keratosis, 3 cases of squamous cell carcinoma, 1 case of skin ulcer and 6 cases of basal cell carcinoma. The range of defect after resection of the lesions was 4 cm×3 cm-9 cm×8 cm. The flap area was 5 cm×3 cm-11 cm×9 cm, the flap pedicle width was 2-3 cm, length was 2-4 cm, After surgery, the blood supply of the flap was good without necrosis, the wound were covered by first treatment. After 6-18 months of follow-up, the donor and recipient areas presented natural appearance, no swelling, no paresthesia and facial paralysis, and no recurrence of cancer.Conclusions:The lateral maxillocervical boot-shaped perforator fasciocutaneous flap pedicled with perforating branch of superficial temporal artery has reliable blood supply. Using this flap to repair large soft tissue defects in zygomatic-temporal region has the advantages of simple operation, similar color and texture, and good appearance.

Objective:To investigate the anatomy of lateral maxillocervical boot-shaped perforator fasciocutaneous flap and its clinical effect on repairing soft tissue defect of zygomatic-temporal region.Methods:(1)From December 2017 to December 2020, five fresh adult cadaver specimens were infused with gelatin lead oxidate and underwent one-time arteriography.The X-ray image was imported into Mimics 17.0 software, divided and colored based on the head and face anatomy, and the distribution and anastomosis of the arteries involved in the lateral maxillocervical boot-shaped perforator fasciocutaneous flap were observed.The head and neck samples of another 5 (10 sides) fresh adult cadavers were infused with red latex artery to establish the surgical model, and then dissected layer by layer to investigate the blood supply and the source of perforating artery of this flap.(2) The patients with zygomatic-temporal lesions were treated in the Department of Plastic Surgery, the First Affiliated Hospital of Anhui Medical University.They were treated with the lateral maxillocervical boot-shaped perforator fasciocutaneous flap to repair the wound left after lesion resection. The survival of the flap and the healing of the incision were observed after surgery and the appearance and sensation of donor and recipient sites as well as tumor recurrence were followed up.Results:(1) The pedicle of the lateral maxillocervical boot-shaped perforator fasciocutaneous flap is mainly nourished by the superficial temporal artery and its perforator.The average diameter of the maximum three perforations is (0.44±0.04) mm, (0.90±0.08) mm, (0.73±0.05) mm.The fascial vascular network and subdermal vascular network formed by perforating arteries from superficial temporal artery and branching arteries from facial artery at different layers are the anatomical basis for ensuring blood supply of lateral maxillocervical boot-shaped perforator fasciocutaneous flap. (2) A total of 12 patients with zygomatic-temporal lesions were treated clinically, including 8 males and 4 females aged 42-79 years, including 2 cases of senile sebaceous keratosis, 3 cases of squamous cell carcinoma, 1 case of skin ulcer and 6 cases of basal cell carcinoma. The range of defect after resection of the lesions was 4 cm×3 cm-9 cm×8 cm. The flap area was 5 cm×3 cm-11 cm×9 cm, the flap pedicle width was 2-3 cm, length was 2-4 cm, After surgery, the blood supply of the flap was good without necrosis, the wound were covered by first treatment. After 6-18 months of follow-up, the donor and recipient areas presented natural appearance, no swelling, no paresthesia and facial paralysis, and no recurrence of cancer.Conclusions:The lateral maxillocervical boot-shaped perforator fasciocutaneous flap pedicled with perforating branch of superficial temporal artery has reliable blood supply. Using this flap to repair large soft tissue defects in zygomatic-temporal region has the advantages of simple operation, similar color and texture, and good appearance.