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Volume 9 ， Issue 5 ， 2022
- Abstract：Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition" . However, much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons’ surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (<80 ml) and large-volume (≥80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons’ skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.Keywords：Transurethral plasmakinetic resection of prostate;Benign prostatic hyperplasia;Recommendation;Treatment;Guideline16|0|0Updated：2023-02-28
POSITION ARTICLE AND GUIDELINE
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Abstract：Background:After renal trauma, surgical treatment is vital, but sometimes there may be loss of function due to fibrosis. This study aimed to evaluate the effect of autologous omentum flaps on injured renal tissues in a rat model.Methods:A total of 30 Wistar albino rats were included and randomly divided equally into a control group and four intervention groups. Iatrogenic renal injuries were repaired using a surgical technique (primary repair 1 group and primary repair 2 group) or transposition of the autologous omentum (omentum repair 1 group and omentum repair 2 group). Blood samples were taken preoperatively and on the 1st and 7th postoperative days in all groups and on the 18th postoperative day in the control and two intervention groups. All rats were sacrificed on the 7th or 18th day postoperatively, and their right kidneys were taken for histopathological evaluation.Results:The mean urea level significantly decreased from day 1 to day 7 and from day 1 to day 18 in the omentum repair 2 group (P=0.005 and P=0.004, respectively). There were no other significant changes in urea or creatinine levels within the intervention groups (P>0.05). There was no significant correlation between the urea and creatinine levels and the histological scores (P>0.05). The primary repair 1 and 2 groups had significantly higher median granulation and inflammation scores in the kidney specimen than the control and omentum repair groups (P<0.05). The omentum repair 2 group had significantly lower median granulation and inflammation scores in the surrounding tissues than the primary repair 2 group (P<0.05). The completion score for the healing process in the kidney specimen was significantly higher in the omentum repair groups than in the primary repair groups (P<0.05). Granulation degree in the kidney specimen was strongly and positively correlated with the inflammation degree (r=0.824, P<0.001) and foreign body reaction in the kidney specimen (r=0.872, P<0.001), and a strong and negative correlation with the healing process completion score in the kidney specimen (r=–0.627, P=0.001). Inflammation degree in the kidney specimen was strongly and positively correlated with the foreign body reaction in the kidney specimen (r=0.731, P=0.001), and strongly and negatively correlated with the healing process completion score in the kidney specimen (r=–0.608, P=0.002).Conclusions:Autologous omentum tissue for kidney injury repair attenuated inflammation and granulation. Additionally, the use of omental tissue to facilitate healing of kidney injury may theoretically lead to a more effective healing process with reduced fibrosis, tissue and function loss.Keywords：Omentum;rat;regeneration;Renal trauma10|0|0Updated：2023-02-28 -
Abstract：Background:In sepsis, vitamin D binding protein (VDBP) has been shown to be low-expressed. The current study examined the relationship between serum VDBP level and liver injury in sepsis patients, as well as in a mouse model for sepsis and in cultured liver epithelial cell line exposed to lipopolysaccharide (LPS).Methods:The human study included 78 sepsis patients and 50 healthy volunteers. Sepsis patients were categorized into sepsis survivor group (n=43) and sepsis non-survivor group (n=35) based on 28-day mortality for data analysis. Adult male C57BL/6 mice were subjected to cecal ligation and puncture (CLP). Serum samples were collected on days 1, 3, 5 and 7 to determine the levels of VDBP, 25-hydroxyvitamin D [25(OH)D3], 1,25-dihydroxyvitamin D [1,25(OH)2D3], interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Potential protective effects of VDBP overexpression against LPS-induced liver damage were examined in cultured THLE2 cells.Results:Serum levels of VDBP, 25(OH)D3, and 1,25(OH)2D3 were significantly lower in sepsis patients vs. the healthy control (P<0.001), as well as in the sepsis non-survivor group vs. the sepsis survivor group (P<0.001, P=0.0338, or P=0.0013, respectively). Lower serum VDBP level was associated with higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (r=–0.2565, P=0.0234) and Sequential Organ Failure Assessment (SOFA) score (r=–0.3522, P=0.0016), but lower serum albumin (ALB, r=0.4628, P<0.001) and total protein (TP, r=0.263, P=0.02). In CLP mice, there was a 5-day period of serum VDBP reduction, followed by return towards the baseline on day 7. VDBP was also decreased in LPS-treated THLE2 cells (P<0.001). VDBP overexpression reduced LPS-induced THLE2 damage. Reduced damage was associated with decreased oxidative stress and inactivation of the c-Jun N-terminal kinase signaling pathway.Conclusions:VDBP may be protective against sepsis-induced liver injury.Keywords：Vitamin D binding protein;sepsis;human;mouse;liver;injury;c-Jun N-terminal kinase20|0|0Updated：2023-02-28 -
Abstract：Background:Early diagnosis and classification of infections increase the cure rate while decreasing complications, which is significant for severe infections, especially for war surgery. However, traditional methods rely on laborious operations and bulky devices. On the other hand, point-of-care (POC) methods suffer from limited robustness and accuracy. Therefore, it is of urgent demand to develop POC devices for rapid and accurate diagnosis of infections to fulfill on-site militarized requirements.Methods:We developed a wave-shaped microfluidic chip (WMC) assisted multiplexed detection platform (WMC-MDP). WMC-MDP reduces detection time and improves repeatability through premixing of the samples and reaction of the reagents. We further combined the detection platform with the streptavidin–biotin (SA-B) amplified system to enhance the sensitivity while using chemiluminescence (CL) intensity as signal readout. We realized simultaneous detection of C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) on the detection platform and evaluated the sensitivity, linear range, selectivity, and repeatability. Finally, we finished detecting 15 samples from volunteers and compared the results with commercial ELISA kits.Results:Detection of CRP, PCT, and IL-6 exhibited good linear relationships between CL intensities and concentrations in the range of 1.25–40 μg/ml, 0.4–12.8 ng/ml, and 50–1600 pg/ml, respectively. The limit of detection of CRP, PCT, and IL-6 were 0.54 μg/ml, 0.11 ng/ml, and 16.25 pg/ml, respectively. WMC-MDP is capable of good adequate selectivity and repeatability. The whole detection procedure takes only 22 min that meets the requirements of a POC device. Results of 15 samples from volunteers were consistent with the results detected by commercial ELISA kits.Conclusions:WMC-MDP allows simultaneous, rapid, and sensitive detection of CRP, PCT, and IL-6 with satisfactory selectivity and repeatability, requiring minimal manipulation. However, WMC-MDP takes advantage of being a microfluidic device showing the coefficients of variation less than 10% enabling WMC-MDP to be a type of point-of-care testing (POCT). Therefore, WMC-MDP provides a promising alternative to POCT of multiple biomarkers. We believe the practical application of WMC-MDP in militarized fields will revolutionize infection diagnosis for soldiers.Keywords：Point-of-care testing (POCT);Infection markers;Wave-shaped microfluidic chip;chemiluminescence;Multiplex detection10|0|0Updated：2023-02-28 -
Abstract：Background:Currently, there is no formal consensus regarding a standard classification for gastric cancer (GC) patients with <16 retrieved lymph nodes (rLNs). Here, this study aimed to validate a practical lymph node (LN) staging strategy to homogenize the nodal classification of GC cohorts comprising of both <16 (Limited set) and ≥16 (Adequate set) rLNs.Methods:All patients in this study underwent R0 gastrectomy. The overall survival (OS) difference between the Limited and Adequate sets from a large Chinese multicenter dataset was analyzed. Using the 8th American Joint Committee on Cancer (AJCC) pathological nodal classification (pN) for GC as base, a modified nodal classification (N’) resembling similar analogy as the 8th AJCC pN classification was developed. The performance of the proposed and 8th AJCC GC subgroups was compared and validated using the Surveillance, Epidemiology, and End Results (SEER) dataset comprising of 10,208 multi-ethnic GC cases.Results:Significant difference in OS between the Limited and Adequate sets (corresponding N0–N3a) using the 8th AJCC system was observed but the OS of N0limited vs. N1adequate, N1limited vs. N2adequate, N2limited vs. N3aadequate, and N3alimited vs. N3badequate subgroups was almost similar in the Chinese dataset. Therefore, we formulated an N’ classification whereby only the nodal subgroups of the Limited set, except for pT1N0M0 cases as they underwent less extensive surgeries (D1 or D1 + gastrectomy), were re-classified to one higher nodal subgroup, while those of the Adequate set remained unchanged (N’0=N0adequate+pT1N0M0limited, N’1=N1adequate+N0limited (excluding pT1N0M0limited), N’2=N2adequate+N1limited, N’3a=N3aadequate+N2limited, and N’3b=N3badequate+N3alimited). This N’ classification demonstrated less heterogeneity in OS between the Limited and Adequate subgroups. Further analyses demonstrated superior statistical performance of the pTN’M system over the 8th AJCC edition and was successfully validated using the SEER dataset.Conclusions:The proposed nodal staging strategy was successfully validated in large multi-ethnic GC datasets and represents a practical approach for homogenizing the classification of GC cohorts comprising of patients with <16 and ≥16 rLNs.Keywords：Lymph nodes;Limited;Adequate;gastric cancer;American Joint Committee on Cancer;Tumor-nodemetastasis;Staging system;Overall survival9|0|0Updated：2023-02-28 -
Abstract：Background:Stemness and chemoresistance contribute to cervical cancer recurrence and metastasis. In the current study, we determined the relevant players and role of N6-methyladenine (m6A) RNA methylation in cervical cancer progression.Methods:The roles of m6A RNA methylation and centromere protein K (CENPK) in cervical cancer were analyzed using bioinformatics analysis. Methylated RNA immunoprecipitation was adopted to detect m6A modification of CENPK mRNA. Human cervical cancer clinical samples, cell lines, and xenografts were used for analyzing gene expression and function. Immunofluorescence staining and the tumorsphere formation, clonogenic, MTT, and EdU assays were performed to determine cell stemness, chemoresistance, migration, invasion, and proliferation in HeLa and SiHa cells, respectively. Western blotting analysis, co-immunoprecipitation, chromatin immunoprecipitation, and luciferase reporter, cycloheximide chase, and cell fractionation assays were performed to elucidate the underlying mechanism.Results:Bioinformatics analysis of public cancer datasets revealed firm links between m6A modification patterns and cervical cancer prognosis, especially through ZC3H13-mediated m6A modification of CENPK mRNA. CENPK expression was elevated in cervical cancer, associated with cancer recurrence, and independently predicts poor patient prognosis [hazard ratio=1.413, 95% confidence interval=1.078–1.853, P=0.012]. Silencing of CENPK prolonged the overall survival time of cervical cancer-bearing mice and improved the response of cervical cancer tumors to chemotherapy in vivo (P<0.001). We also showed that CENPK was directly bound to SOX6 and disrupted the interactions of CENPK with β-catenin, which promoted β-catenin expression and nuclear translocation, facilitated p53 ubiquitination, and led to activation of Wnt/β-catenin signaling, but suppression of the p53 pathway. This dysregulation ultimately enhanced the tumorigenic pathways required for cell stemness, DNA damage repair pathways necessary for cisplatin/carboplatin resistance, epithelial-mesenchymal transition involved in metastasis, and DNA replication that drove tumor cell proliferation.Conclusions:CENPK was shown to have an oncogenic role in cervical cancer and can thus serve as a prognostic indicator and novel target for cervical cancer treatment.Keywords：N6-methyladenosine;Centromere protein K;cervical cancer;Stemness;Chemoresistance13|0|0Updated：2023-02-28
RESEARCH
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Abstract：Bacteria can evolve rapidly by acquiring new traits such as virulence, metabolic properties, and most importantly, antimicrobial resistance, through horizontal gene transfer (HGT). Multidrug resistance in bacteria, especially in Gram-negative organisms, has become a global public health threat often through the spread of mobile genetic elements. Conjugation represents a major form of HGT and involves the transfer of DNA from a donor bacterium to a recipient by direct contact. Conjugative plasmids, a major vehicle for the dissemination of antimicrobial resistance, are selfish elements capable of mediating their own transmission through conjugation. To spread to and survive in a new bacterial host, conjugative plasmids have evolved mechanisms to circumvent both host defense systems and compete with co-resident plasmids. Such mechanisms have mostly been studied in model plasmids such as the F plasmid, rather than in conjugative plasmids that confer antimicrobial resistance (AMR) in important human pathogens. A better understanding of these mechanisms is crucial for predicting the flow of antimicrobial resistance-conferring conjugative plasmids among bacterial populations and guiding the rational design of strategies to halt the spread of antimicrobial resistance. Here, we review mechanisms employed by conjugative plasmids that promote their transmission and establishment in Gram-negative bacteria, by following the life cycle of conjugative plasmids.Keywords：Horizontal gene transfer;Antimicrobial resistance;Conjugative plasmids;Type IV secretion system;Restriction-modification systems;SOS response;Entry exclusion;Fertility inhibition7|0|0Updated：2023-02-28 -
Abstract：Spinal cord injury (SCI) is a serious traumatic disease of the central nervous system, which can give rise to the loss of motor and sensory function. Due to its complex pathological mechanism, the treatment of this disease still faces a huge challenge. Hydrogels with good biocompatibility and biodegradability can well imitate the extracellular matrix in the microenvironment of spinal cord. Hydrogels have been regarded as promising SCI repair material in recent years and continuous studies have confirmed that hydrogel-based therapy can effectively eliminate inflammation and promote spinal cord repair and regeneration to improve SCI. In this review, hydrogel-based multimodal therapeutic strategies to repair SCI are provided, and a combination of hydrogel scaffolds and other therapeutic modalities are discussed, with particular emphasis on the repair mechanism of SCI.Keywords：spinal cord injury;Injectable hydrogels;Hydrogel scaffolds;Multimodal therapy12|3|0Updated：2023-02-28 -
Abstract：Idiopathic pulmonary fibrosis (IPF) is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function. Chronic inflammation has been demonstrated to be the pathological basis of fibrosis. Emerging studies have revealed that most interleukin-17 (IL-17) isoforms are essential for the mediation of acute and chronic inflammation via innate and adaptive immunity. Overexpression or aberrant expression of IL-17 cytokines contributes to various pathological outcomes, including the initiation and exacerbation of IPF. Here, we aim to provide an overview of IL-17 family members in the pathogenesis of IPF.Keywords：Interleukin-17 (IL-17) family;IL-17 receptor;Inflammation;Idiopathic pulmonary fibrosis11|0|0Updated：2023-02-28 -
Abstract：Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in approximately 15%–20% of breast cancer cases. HER2 is a member of the epidermal growth factor receptor (EGFR) family with tyrosinase kinase activity, and its overexpression is linked to poor prognosis and shorter progression-free survival (PFS) and overall survival (OS). Among various treatment options, HER2-targeting monoclonal antibodies and tyrosine kinase inhibitors (TKIs) have mostly been applied in recent decades to treat HER2-positive (HER2+) breast cancer patients. Although positive clinical outcomes were documented in both advanced disease and neoadjuvant settings, the development of resistance mechanisms to such approaches has been one of the major challenges with the continuous usage of these drugs. In addition, patients who experience disease progression after treatment with multiple HER2-targeted therapies often have limited treatment options. The Food and Drug Administration (FDA) has recently approved a new TKI (i.e., tucatinib) for use in combination with immunotherapy and/or chemotherapeutic agents for the treatment of advanced-stage/metastatic HER2+ breast cancer. This review highlights recent updates on the efficacy of tucatinib-based therapeutic approaches in experimental models as well as in the clinical settings of HER2+ breast cancer.Keywords：HER2-positive (HER2+);Breast cancer;Targeted therapy;Tucatinib;Immunotherapy14|0|1Updated：2023-02-28
REVIEW
- Keywords：mitochondria;Succinylation;phosphorylation;Glutaminase13|0|0Updated：2023-02-28
LETTER TO THE EDITOR
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