BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

Objective:To investigate clinical efficacy of parasacral perforator flap (PPF) on postoperative wound healing in pilonidal sinus diseases (PSDs).Methods:The surgery steps were as follows: (1) To preoperatively detect parasacral perforator arteries with the handhold Doppler probe and mark them; (2) To remove the infected and necrotic tissues of PSDs completely; (3) To design the PPF according to the wound size and the parasacral perforator arteries' localization; (4) To harvest the flap from the gluteus maximus muscle surface and transfer it to the wound without tension. Several data were documented, including surgical duration, flap length, flap width, drainage tube placement duration, hospital stay, duration from operation to stitch removal, postsurgical complications and recurrence.Results:There were six patients with PSDs whose postoperative wound healing was repaired by PPF, admitted in our department from March 2021 to March 2023. Of them, five were male and one was female. Their median age was 24 (range: 18-33) years old. Their median surgical duration was 165 (range: 134-207) minutes, median length of PPF was 8 (range: 7-11) cm, median width of PPF was 3 (range: 3-4) cm, mean duration of drainage tube placement was 8 (range: 4-17) days, mean hospital stay was 13 (range: 6-23) days, mean duration from operation to stitch removal was 14 (range: 14-17) days, median follow-up time was 6-16 months. Incisions of all six cases achieved first-intention healing without early- or late-stage complications. No recurrence occurred during follow-up. All patients involved were satisfied with their clinical efficacy.Conclusion:The utility of PPF in postoperative wound healing of PPDs was effective, safe and reliable.

OBJECTIVE: A prospective randomized controlled study was conducted to investigate the early postoperative analgesic effectiveness of using liposomal bupivacaine (LB) for local infiltration anesthesia (LIA) in unicompartmental knee arthroplasty (UKA). METHODS: Between January 2024 and July 2024, a total of 80 patients with knee osteoarthritis (KOA) who met the selection criteria were enrolled in the study. Patients were randomly assigned to either the LB group or the "cocktail" group in a 1∶1 ratio using a random number table, with 40 patients in each group. Baseline characteristics, including gender, age, body mass index, operated side, Kellgren-Lawrence grade, and preoperative American Society of Anesthesiologists (ASA) classification, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee joint range of motion, showed no significant difference between the two groups ( P>0.05). Both groups received LIA and comprehensive pain management. The surgical duration, incision length, pain-related indicators [resting and activity visual analogue scale (VAS) scores, total dosage of oral morphine, WOMAC scores], knee joint range of motion, first ambulation time after operation, length of hospital stay, and postoperative adverse events. RESULTS: There was no significant difference between the two groups in surgical duration, incision length, first ambulation time after operation, length of hospital stay, total dosage of oral morphine, and pre-discharge satisfaction with surgery and WOMAC scores ( P>0.05). At 4, 12, and 24 hours after operation, the resting and activity VAS scores in the "cocktail" group were lower than those in the LB group; at 60 and 72 hours postoperatively, the resting VAS scores in the LB group were lower than those in the "cocktail" group, with the activity VAS scores also being lower at 60 hours; all showing significant differences ( P<0.05). There was no significant difference in the above indicators between the two groups at other time points ( P>0.05). On the second postoperative day, the sleep scores of the LB group were significantly higher than those of the "cocktail" group ( P<0.05), while there was no significant difference in sleep scores on the day of surgery and the first postoperative day ( P>0.05). Additionally, the incidence of complications showed no significant difference between the two groups ( P>0.05). CONCLUSION The use of LB for LIA in UKA can provide prolonged postoperative pain relief; however, it does not demonstrate a significant advantage over the "cocktail" method in terms of short-term analgesic effects or reducing opioid consumption and early functional recovery after UKA. Nevertheless, LB may help reduce postoperative sleep disturbances, making it a recommended option for UKA patients with cardiovascular diseases and insomnia or other mental health issues.
Aged ; Female ; Humans ; Male ; Middle Aged ; Anesthesia, Local/methods* ; Anesthetics, Local/administration & dosage* ; Arthroplasty, Replacement, Knee/methods* ; Bupivacaine/administration & dosage* ; Liposomes ; Osteoarthritis, Knee/surgery* ; Pain Measurement ; Pain, Postoperative/prevention & control* ; Prospective Studies ; Treatment Outcome

Objective:To investigate clinical efficacy of parasacral perforator flap (PPF) on postoperative wound healing in pilonidal sinus diseases (PSDs).Methods:The surgery steps were as follows: (1) To preoperatively detect parasacral perforator arteries with the handhold Doppler probe and mark them; (2) To remove the infected and necrotic tissues of PSDs completely; (3) To design the PPF according to the wound size and the parasacral perforator arteries' localization; (4) To harvest the flap from the gluteus maximus muscle surface and transfer it to the wound without tension. Several data were documented, including surgical duration, flap length, flap width, drainage tube placement duration, hospital stay, duration from operation to stitch removal, postsurgical complications and recurrence.Results:There were six patients with PSDs whose postoperative wound healing was repaired by PPF, admitted in our department from March 2021 to March 2023. Of them, five were male and one was female. Their median age was 24 (range: 18-33) years old. Their median surgical duration was 165 (range: 134-207) minutes, median length of PPF was 8 (range: 7-11) cm, median width of PPF was 3 (range: 3-4) cm, mean duration of drainage tube placement was 8 (range: 4-17) days, mean hospital stay was 13 (range: 6-23) days, mean duration from operation to stitch removal was 14 (range: 14-17) days, median follow-up time was 6-16 months. Incisions of all six cases achieved first-intention healing without early- or late-stage complications. No recurrence occurred during follow-up. All patients involved were satisfied with their clinical efficacy.Conclusion:The utility of PPF in postoperative wound healing of PPDs was effective, safe and reliable.

Tumor recurrence is one of the major life-threatening complications after liver transplantation for liver cancer. In addition to the common mechanisms underlying tumor recurrence, another unavoidable problem is that the immunosuppressive therapeutic regimen after transplantation could promote tumor recurrence and metastasis. Transplant oncology is an emerging field that addresses oncological challenges in transplantation. In this context, a comprehensive therapeutic management approach is required to balance the anti-tumor treatment and immunosuppressive status of recipients. Double-negative T cells (DNTs) are a cluster of heterogeneous cells mainly consisting of two subsets stratified by T cell receptor (TCR) type. Among them, TCRαβ⁺ DNTs are considered to induce immune suppression in immune-mediated diseases, while TCRγδ⁺ DNTs are widely recognized as tumor killers. As a composite cell therapy, healthy donor-derived DNTs can be propagated to therapeutic numbers in vitro and applied for the treatment of several malignancies without impairing normal tissues or being rejected by the host. In this work, we summarized the biological characteristics and functions of DNTs in oncology, immunology, and transplantation. Based on the multiple roles of DNTs, we propose that a new balance could be achieved in liver transplant oncology using them as an off-the-shelf adoptive cell therapy (ACT).
Humans ; T-Lymphocytes ; Immunotherapy, Adoptive ; Neoplasm Recurrence, Local ; Transplantation, Homologous ; Cell- and Tissue-Based Therapy

Objective:To observe the efficacy and safety of the M receptor antagonist Bencycloquidium bromide nasal spray in treatment of seasonal allergic rhinitis with runny nose as the main symptom. Methods:From August 2021 to September 2021, 134 patients with seasonal allergic rhinitis were enrolled in the otolaryngology Outpatient Department of Peking University Third Hospital, First Affiliated Hospital of Harbin Medical University and China-Japanese Friendship Hospital of Jilin University, including 71 males and 63 females, with a median age of 38 years. TNSS score and visual analogue scale（VAS） of total nasal symptoms were observed during 2 weeks of treatment with Bencycloquidium bromide nasal spray. Results:TNSS score decreased from （8.89±3.31） on day 0 to （3.71±2.51） on day 14（P<0.001）, VAS score of nasal symptoms decreased from （24.86±7.40） on day 0 to （6.84±5.94） on day 14（P<0.001）, VAS score of rhinorrhoea decreased from （6.88±2.06） on day 0 to （1.91±1.81） on day 14（P<0.001）. Rhinoconjunctivitis quality of life questionnaire（RQLQ） score decreased from （94.63±33.35） on day 0 to （44.95±32.28） on day 14（P<0.001）. The incidence of adverse reaction was low and no serious adverse events occurred during the whole experiment. Conclusion:Bencycloquidium bromide nasal spray has significant efficacy and good safety in the treatment of seasonal allergic rhinitis.
Male ; Female ; Humans ; Adult ; Rhinitis, Allergic, Seasonal/drug therapy* ; Nasal Sprays ; Quality of Life ; Administration, Intranasal ; Rhinorrhea ; Double-Blind Method ; Treatment Outcome ; Rhinitis, Allergic/drug therapy*

OBJECTIVE To evalu ate the effects of perimenopausal one-day outpatient multidisciplinary model on the cognition of women to menopause hormone therapy （MHT）. METHODS The perimenopausal one-day outpatient service opened by the Third Affiliated Hospital of Chongqing Medical University in 2017 was introduced ，which was participated by doctors ，pharmacists， nutritionists，music psychotherapists ，nurses and other multidisciplinary members to provide systematic ，all-round，humanistic and face-to-face group science popularization and education ，practical experience and Q&A for women in perimenopause or about to enter perimenopause （called“students”）. The students who participated in one-day outpatient service in 2020 were selected as the survey object ， and the questionnaire was CMEI2020KPYJ（ZAMM）00206] designed to analyze the understanding of perimenopausal syndrome，awareness rate of MHT ，willingness to use and concerns. RESULTS A total of 295 students completed the questionnaire. Compared with before participation ， after participated in one-day outpatient service ，the cognition level of the students were all improved significantly ，including perimenopausal age （96.61％ vs. 99.32％，P＝0.037），the importance of perimenopausal health care knowledge （91.19％ vs. 96.95％，P＜0.001），whether the perimenopausal syndrome needs treatment （88.47％ vs. 99.32％，P＜0.001），willingness to use MHT （70.59％ vs. 94.48％ ，P＜0.001），MHT treatment timing （60.50％ vs. 95.17％ ，P＜0.001），reducing the risk of cardiovascular disease （51.68％ vs. 96.55％ ，P＜0.001），delaying aging （69.75％ vs. 97.59％ ，P＜0.001），preventing osteoporosis（65.13％ vs. 97.59％），P＜0.001）；the medical staff were higher than the non-medical staff （P＜0.05）. Totally 90％ of the students said they had gained knowledge about the prevention and treatment of common diseases ，nutrition and guidance， psychological regulation guidance hormone therapy related knowledges and exercise methods ；the proportion of the students who were willing to use MHT for 1 to 5 years（31.09％ vs. 47.93％）increased significantly. The proportion of the students who concerned about the risk of thrombosis （60.24％ vs. 36.81％），weight gain （59.64％ vs. 14.84％）and life-long dependence （52.41％ vs. 18.13％）was significantly reduced ，but that of the students who concerned about cancer risk was not diminished. From 2017 to 2020，the utilization rate of MHT was increased from 2.22％ to 62.16％ in non-medical staff among the students. CONCLUSIONS The multidisciplinary model of perimenopausal one-day outpatient service can improve the awareness of MHT among perimenopausal women ，eliminate misunderstandings ，and increase the utilization rate of MHT.

This study aimed to uncover underlying mechanisms and promising intervention targets of heart failure (HF)-related stroke. HF-related dataset GSE42955 and stroke-related dataset GSE58294 were obtained from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was conducted to identify key modules and hub genes. Gene Ontology (GO) and pathway enrichment analyses were performed on genes in the key modules. Genes in HF-and stroke-related key modules were intersected to obtain common genes for HF-related stroke, which were further intersected with hub genes of stroke-related key modules to obtain key genes in HF-related stroke. Key genes were functionally annotated through GO in the Reactome and Cytoscape databases. Finally, key genes were validated in these two datasets and other datasets. HF-and stroke-related datasets each identified two key modules. Functional enrichment analysis indicated that protein ubiquitination, Wnt signaling, and exosomes were involved in both HF-and stroke-related key modules. Additionally, ten hub genes were identified in stroke-related key modules and 155 genes were identified as common genes in HF-related stroke. OTU deubiquitinase with linear linkage specificity (OTULIN) and nuclear factor interleukin 3-regulated (NFIL3) were determined to be the key genes in HF-related stroke. Through functional annotation, OTULIN was involved in protein ubiquitination and Wnt signaling, and NFIL3 was involved in DNA binding and transcription. Importantly, OTULIN and NFIL3 were also validated to be differentially expressed in all HF and stroke groups. Protein ubiquitination, Wnt signaling, and exosomes were involved in HF-related stroke. OTULIN and NFIL3 may play a key role in HF-related stroke through regulating these processes, and thus serve as promising intervention targets.

In clinical work, it is observed that keloid has significantly different characteristics from other types of scar such as hypertrophic scar. The growth of keloid usually exceeds the margin of original wound and continuously invades the surrounding skin, and keloid has a certain recurrence rate after various treatment measures such as surgery and glucocorticoid injection, etc. The above phenomenon suggests that keloid has certain tumor characteristics, and we cannot judge keloid from the perspective of scar alone. This article attempts to re-describe the pathogenesis of keloid from the perspective of tumor and summarizes the tumor characteristics of keloid from self-sufficiency of growth signal, avoidance of apoptosis, and abnormal angiogenesis, etc.

Objective:To explore the clinical effects of partially de-epithelized local flaps in repairing tubercular chest wall defects.Methods:A retrospective observational study was conducted. From April 2010 to February 2021, twelve patients who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of the Eighth Medical Center of PLA General Hospital, including 9 males and 3 females with age of (42±18) years. The sizes of tubercular chest wall defects of patients were ranged from 4 cm×3 cm×2 cm to 16 cm×8 cm×5 cm, which were all repaired with partial de-epithelized local flaps. The widths of flaps were equal to the widths of the defects, and the lengths of flaps were 2 cm longer than those of the defects. In one patient, the local flap was too large to close the donor site directly by suturing, so an autologous back free medium thickness skin graft was used for repair. In other patients, the collection areas of local flaps were small, and the donor areas of flaps were directly closed. The duration of operation, intraoperative bleeding, and postoperative drainage volume and indwelling time of drainage tube were observed and recorded. In two weeks after operation, the survival, color, and texture of flaps, the presence of subcutaneous hydrops and skin ulcer, and donor site healing including wound disruption, local infection, hematoma were observed. Chest X-ray, CT scan, or nuclear magnetic resonance imaging was performed in one month after operation to check whether new local hydrops and bone destruction occurred in the chest wall defects and the concomitant tuberculose focus of patients. All patients were followed up for more than 6 months to record whether the surgical incisions of the chest wall defects of the patients were complicated by hypertrophic scar, redness, swelling, and sinus.Results:In surgery, the patient had (104±18) min of operation duration, (119±53) mL of intraoperative bleeding, (134±49) mL of cumulative drainage of drainage tube, and (5.3±1.7) days of drainage tube indwelling time. In two weeks after operation, all the grafted local flaps survived, and the color and texture of flaps were similar to the surrounding normal skin. One patient had fluid leakage from the incision of chest wall defect area with the incision partially dehisced, which healed well after a phase Ⅱ operation; no wound infection, subcutaneous hydrops, or wound rupture occurred in other patients. The incisions of donor sites in all the patients healed well and no wound disruption, local infection, or hematoma occurred. One month after operation, no new bone destruction was observed in the operative region by chest imaging examination. Patients were followed up for 6 to 96 months, with one patient having wound swelling, ulceration, and sinus in the operative area of the chest wall defect in 12 months after surgery, which healed after phase Ⅱ operation; the incisions of chest wall defect wounds in other patients healed well and had no scar, redness and swelling, or sinus.Conclusions:Partially de-epithelized local flap could be used in repairing tubercular chest wall defect wounds, with the advantages of flexible flap design, minimal donor site injury, and good postoperative wound healing.