OBJECTIVE: To compare the effectiveness of single-stage vascularized lymph node transfer (VLNT) combined with lymphaticovenular anastomosis (LVA) and liposuction (LS) (3L) versus LVA combined with LS (2L) for the treatment of moderate-to-late stage upper limb lymphedema following breast cancer surgery. METHODS: A retrospective analysis was conducted on the clinical data of 16 patients with moderate-to-late stage upper limb lymphedema after breast cancer surgery, treated between June 2022 and June 2024, who met the selection criteria. Patients were divided into 3L group (n=7) and 2L group (n=9) based on the surgical approach. There was no significant difference (P>0.05) in baseline data between the groups, including age, body mass index, duration of edema, volume of liposuction, International Society of Lymphology (ISL) stage, preoperative affected limb volume, preoperative circumferences of the affected limb at 12 levels (from 4 cm distal to the wrist to 42 cm proximal to the wrist), preoperative Lymphoedema Quality of Life (LYMQoL) score, and frequency of cellulitis episodes. The 2L group underwent LS on the upper arm and proximal forearm and LVA on the middle and distal forearm. The 3L group received additional VLNT in the axilla, with the groin serving as the donor site. Outcomes were assessed included the change in affected limb volume at 12 months postoperatively, and comparisons of limb circumferences, LYMQoL score, and frequency of cellulitis episodes between preoperative and 12-month postoperative. Ultrasound evaluation was performed at 12 months in the 3L group to assess lymph node viability. RESULTS: Both groups were followed up 12-20 months, with an average of 15.13 months. There was no significant difference in the follow-up time between the groups (t=-1.115, P=0.284). All surgical incisions healed by first intention. No adverse events, such as flap infection or necrosis, occurred in the 3L group. At 12 months after operation, ultrasound confirmed good viability of the transferred lymph nodes in the 3L group. Palpation revealed significant improvement in skin fibrosis and improved skin softness in both groups. Affected limb volume significantly decreased in both groups postoperatively (P<0.05). The reduction in limb volume significantly greater in the 3L group compared to the 2L group (P<0.05). Circumferences at all 12 measured levels significantly decreased in both groups compared to preoperative values (P<0.05). The reduction in circumference at all 12 levels was better in the 3L group than in the 2L group, with significant differences observed at 7 levels (8, 12, 16, 30, 34, 38, and 42 cm) proximal to the wrist (P<0.05). Both groups showed significant improvement in the frequency of cellulitis episodes and LYMQoL scores postoperatively (P<0.05). While the improvement in LYMQoL scores at 12 months did not differ significantly between groups (P>0.05), the reduction in cellulitis episodes was significantly greater in the 3L group compared to the 2L group (P<0.05). CONCLUSION The combination of VLNT+LVA+LS provides more durable and comprehensive outcomes for moderate-to-late stage upper limb lymphedema after breast cancer surgery compared to LVA+LS, offering an improved therapeutic solution for patients.
Humans ; Female ; Lipectomy/methods* ; Retrospective Studies ; Anastomosis, Surgical/methods* ; Lymphedema/etiology* ; Middle Aged ; Upper Extremity/surgery* ; Breast Neoplasms/surgery* ; Lymph Nodes/blood supply* ; Adult ; Lymphatic Vessels/surgery* ; Iliac Artery/surgery* ; Postoperative Complications/surgery* ; Perforator Flap/blood supply* ; Treatment Outcome ; Mastectomy/adverse effects* ; Quality of Life ; Aged

Virus-induced senescence (VIS) is a significant biological phenomenon, which is associated with declining immune function, accelerating aging process and causing aging-related diseases. A variety of common viruses, including RNA viruses (such as SARS-CoV-2), DNA viruses (such as herpesviruses and hepatitis B virus), and prions can cause VIS in host cells. The primary mechanisms include abnormal activation of the cGAS-STING signaling pathway, DNA damage response, and potential correlations with the integrated stress response due to intracellular phase separation. Viral infection and cellular senescence influence each other: cellular senescence serves as a defense to restrict viral replication and transmission, while some viruses exploit cellular senescence to enhance their infectivity and replication. Understanding the mechanisms of VIS is conducive to the development of therapeutic strategies for viral infections and promotion of healthy aging. However, there is lack of research on therapeutic targets and drug development in this field so far. Although senolytics may be effective for anti-senescent cells therapy, their efficacy for VIS needs evidence from further clinical trials. This article reviews the research progress on the connection between viral infection and cellular senescence, to provide insights for the prevention and treatment of aging related diseases.
Humans ; Cellular Senescence/physiology* ; Virus Diseases/physiopathology* ; Signal Transduction ; Nucleotidyltransferases/metabolism* ; DNA Damage ; Virus Replication ; COVID-19 ; Membrane Proteins/metabolism* ; SARS-CoV-2

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

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Objective:To investigate the variations and co-alteration of KRAS and HER-family genes in the patients with ampullary carcinoma.Methods:A total of 37 formalin-fixed paraffin-embedded primary ampullary carcinoma specimens, which were collected at Peking Union Medical College Hospital from April 2019 to October 2024 were analyzed for KRAS and HER-family gene mutations using next-generation sequencing (NGS). Immunohistochemistry (IHC) was performed for HER2 protein expression in HER2 mutation cases and fluorescence in situ hybridization (FISH) for further gene status in HER2 IHC 2+cases.Results:In our cohort (22 males, 15 females; 31-82 years old), KRAS gene mutations were detected in 51.4% (19/37) of cases, with G12D being the most frequent abnormality (7/19), followed by G12V (5/19) and Q61R (3/19). Other variants of KRAS gene included G12C, A146T, N116H, and Q61H (each 1/19). In this cohort, 27.0% (10/37) of cases harbored HER-family gene alterations with most frequently in HER2 (6/10) and HER3 genes (missense mutations mainly). Notably, 3 cases (8.1%, 3/37) with coexistence of KRAS and HER-family genes mutations were recognized in our series, including KRAS p.G12D/HER2 p.V842I/HER2 p.V777L (c.2329 G>T)/HER3 p.Asp581Asn, KRAS p.Q61R/HER4 p.D1018H and KRAS p.G12C/HER2 p.R678Q. Additionally, a mutation of HER3 p.V104L (c.310 G>C) was identified in our population. Moreover, 4 novel mutations including HER3 p.V296E, HER3 p.V920L (c.2758 G>T), HER3 p.Asp581Asn, and HER4 p.D1018H were detected. In 6 tumors with HER2 gene changes (16.2%, 6/37), 5 variants with the high proportion of HER2 p.S310Y (3/6) were revealed. A tumor (HER2 IHC 2+) with HER2 p.S310Y presented HER2 gene amplification confirmed by NGS and FISH, and another one (also HER2 IHC 2+) with HER2 p.L755S possessed HER2 gene amplification determined by FISH assay.Conclusion:In ampullary carcinoma, co-alteration of KRAS and HER-family genes is observed, and HER2 gene mutations account for more than half of HER-family gene abnormities, which may be accompanied by gene amplification.

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 investigate the mutation of PIK3CA, AKT1 and PTEN genes in hormone receptor (HR)-positive and HER2-negative invasive breast cancer.Methods:A total of 44 formalin-fixed paraffin-embedded samples from HR-positive/HER2-negative female patients with breast cancer obtained between January 2020 and July 2024 in Peking Union Medical College Hospital were selected. The mutations of PIK3CA, AKT1 and PTEN genes were analyzed by next-generation sequencing (NGS), and the related clinicopathological characteristics were summarized.Results:In the cohort, 31 out of 44 cases (70.5%) exhibited alterations in the PIK3CA, AKT1 and PTEN genes. Of these, 83.9% (26/31) tumors harbored genetic abnormalities involving one gene, including 21 (47.7%, 21/44) PIK3CA, 2 (4.5%, 2/44) PTEN and 3 (6.8%, 3/44) AKT1 gene mutations. Mutations of both PIK3CA and PTEN genes were found in 16.1% (5/31) of specimens. Among the 26 cases with PIK3CA gene mutations, 13 variants were identified, including E542K, E545K, Q546K, H1047R, H1047L, G1049R, M1043I, C420R, P447_L455del, N345K, N345I, K711N and H1047L/V346G. In addition, 7 mutants of PTEN gene were determined (T319 *, T321Qfs *23, Q245 *, Q171H, L108P, Y68Ifs *6 and V343fs). For AKT1 gene mutation, only E17K was observed.Mutations of PIK3CA/AKT1/PTEN genes are more likely to occur over 40 year-old patients.In this cohort, the PIK3CA V346G mutation (co-existent PIK3CA H1047L) and the PTEN V343fs mutation were not found in previous publications. Conclusion:In addition to the predominance of common loci, PIK3CA and PTEN gene mutations also have rare loci mutations in the breast cancer, warranting further analysis with an expanded sample size.

Objective:To obtain a polyvalent single-chain variable fragment（scFv）against West Nile virus through PEGylation in order to improve its antigen-binding ability and neutralizing activity.Methods:A scFv carrying a C-terminal cysteine residue（scFvC）was constructed by introducing Cys into the C-terminal of scFv against West Nile virus. Then the multimerization of scFvC was achieved by targeting the thiol group of Cys with maleimide-activated polyethylene glycol. ELISA was used to detect the antigen-binding activity of the multivalent scFvC. Pseudovirus-based neutralization assay was used to evaluate the neutralizing activity of the multivalent scFvC in vitro. One-way analysis of variance was used for statistical analysis. Results:The PEGylated scFvC multimers showed higher antigen-binding ability than the monomeric scFvC. In the pseudovirus-based neutralization assay，both monomeric scFvC and PEGylated scFvC multimers showed good neutralizing activity compared with the control group（ P<0.000 1）. Moreover，the PEGylated scFvC multimers showed a more effective ability to block the pseudovirus infection in target cells（ P<0.05），suggesting that the PEGylated scFvC multimers could enhance their function in vitro through avidity effect. Conclusion:In this study，a scFvC targeting West Nile virus is successfully constructed and its polyvalent form is generated through PEGylation，which improves the antigen-binding and neutralizing activity of the parental scFv.

Objective:To explore the application effect of nursing coordination process based on healthcare failure mode and effect analysis (HFMEA) management in the treatment of patients with acute ST-segment elevation myocardial infarction (STEMI), so as to improve clinical treatment efficiency.Methods:In this prospective cohort study, STEMI patients requiring emergency percutaneous coronary intervention (PCI) admitted to the Department of Emergency, Subei People′s Hospital of Jiangsu Province from January to May 2024 were selected by random sampling method. According to the admission time, patients were divided into control group (from January to February 2024, received routine emergency process) and experimental group (from April to May 2024, received nursing coordination process based on HFMEA management). The triage evaluation time, reception time, reporting time of the first electrocardiogram, coming out time of troponin T results, improvement time of preoperative preparation, treatment effect (length of hospital stay, success rate of treatment, nosocomial mortality) and emergency physicians′ satisfaction with nursing work in the two groups were compared.Results:In the 100 STEMI patients, there were 48 cases in the control group, with 23 males and 25 females, aged (61.64 ± 4.37) years old. There were 52 cases in the experimental group, with 26 males and 26 females, aged (62.11 ± 4.61) years old. The triage evaluation time, reception time, reporting time of the first electrocardiogram, coming out time of troponin T results and improvement time of preoperative preparation in the experimental group were (1.65 ± 0.57), (2.46 ± 0.57), (7.58 ± 1.32), (16.43 ± 2.16), (46.18 ± 3.94) min, shorter than (2.48 ± 0.69), (3.41 ± 0.63), (10.69 ± 1.24), (18.66 ± 2.37), (54.37 ± 4.11) min in the control group, the differences were statistically significant ( t values were 4.92-12.12, all P<0.05). The length of hospital stay and nosocomial mortality in the experimental group were (10.16 ± 2.34) d, 3.85% (2/52), lower than (12.38 ± 2.09) d, 16.67% (8/48) in the control group, and success rate of treatment was 90.38% (47/52), higher than 75.00% (36/48) in the control group, the differences were statistically significant ( t=4.99, χ2=4.56, 4.19, all P<0.05). The emergency physicians′ satisfaction with nursing work in the experimental group was (79.43 ± 6.00) points, higher than (64.44 ± 6.54) points in the control group, the difference was statistically significant ( t=11.95, P<0.05). Conclusions:Nursing coordination process based on HFMEA management can effectively improve emergency efficiency in STEMI patients, shorten emergency time and reduce nosocomial mortality.

Objective:To explore the clinical effect of thin superficial circumflex iliac artery perforator flap with venous superdrainage in treatment of wound in extremities.Methods:Clinical data of 20 patients who were treated from January 2018 to January 2024 in the Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University were retrospectively analysed. The soft tissue defects in extremity were reconstructed with thin perforator flaps of superficial iliac circumflex artery with venous superdrainage. There were 13 patients with upper limb defects and 7 with ankle defects. Of the defects, 12 were of trauma, 2 of tumour resection, 3 of scar release surgery and 3 of donor flat harvesting. The defects ranged from 5.0 cm×4.0 cm to 18.0 cm×7.0 cm in size. During the surgery, portable Doppler was used to detect the perforating branches of the superficial rotational iliac artery and design flaps. The flaps were 5.0 cm×5.0 cm to 20.0 cm×7.0 cm in size, including 16 single-lobed flaps, 3 double-lobed flaps and 1 triple-lobed flaps. The flaps were 2-7 mm in thickness, with an average of 4 mm. Based on the distribution of perforators, the flaps carried the superficial helioiliac artery and the accompanying vein, as well as the superficial helioiliac vein. The superficial helioiliac artery and the accompanying vein were anastomosed during the surgery, and the superficial helioiliac vein was anastomosed to the superficial or deep vein of the recipient site for superreflux. The donor sites were all directly sutured and closed. Postoperative follow-up was conducted by visits of outpatient clinic, and via telephone and WeChat interviews. The survival and appearance of the flaps and complications were observed.Results:A total of 22 arteries and 42 veins of the 20 flaps were anastomosed in surgery. All flaps survived. The donor sites were closed in the first stage. No vascular compromise occurred. One patient had early exudate under the flap on the exposed wound of interphalangeal joint, which healed after routine dressing change and drainage. All patients were included in the postoperative follow-up, with a peroid over 5 to 40 months, at 10.8 months in average. The flaps were thin and soft, with good wear resistance and without pigmentation. The healing of donor sites was good except 1 donore site that had early lymphatic leakage, which was cured after compression and drainage. A linear scar left at the donor sites and it was acceptable to the patients.Conclusion:The treatment of defective soft tissue wounds in extremities using thin perforator flap with venous superdrainage of the superficial circumflex iliac artery is safe and feasible. No further flap thinning surgery is required, and there is a reliable clinical effect.