Novel role of circRNAs in the drug resistance of gastric cancer: regulatory mechanisms and future for cancer therapy.

Cancer, including gastric cancer, has become a serious disease that jeopardizes public life. Currently, the main treatment methods are surgery, radiation therapy, and chemotherapy. One of the primary causes of death for patients with gastric cancer is drug resistance. Several mechanisms of anticancer drugs resistance have been reported, including changes in drugs transport and metabolism, mutations in drug targets, changes in DNA repair systems, inhibition of cell apoptosis and autophagy, gastric cancer stem cells, invasion and migration. It is becoming more widely known that non-coding RNAs, like circRNAs, play a critical role in the resistance of drugs used to treat gastric cancer. CircRNAs have a unique structure and function that is related to gastric cancer resistance, cell proliferation, apoptosis, autophagy, DNA repair systems, migration, and invasion. A clear understanding of the molecular mechanism of circRNAs mediated the resistance of gastric cancer drugs will open a new window for the treatment and management of gastric cancer. Therefore, in this review, we will summarize the current mechanism of drug resistance, and finally discuss the molecular mechanism of circRNAs in regulating the development of drug resistance in gastric cancer.

Association of novel DNAH11 variants with asthenoteratozoospermia lead to male infertility.

BACKGROUND: Bi-allelic variants in DNAH11 have been identified as causative factors in Primary Ciliary Dyskinesia, leading to abnormal respiratory cilia. Nonetheless, the specific impact of these variants on human sperm flagellar and their involvement in male infertility remain largely unknown. METHODS: A collaborative effort involving two Chinese reproductive centers conducted a study with 975 unrelated infertile men. Whole-exome sequencing was employed for variant screening, and Sanger sequencing confirmed the identified variants. Morphological and ultrastructural analyses of sperm were conducted using Scanning Electron Microscopy and Transmission Electron Microscopy. Western Blot Analysis and Immunofluorescence Analysis were utilized to assess protein levels and localization. ICSI was performed to evaluate its efficacy in achieving favorable pregnancy outcomes for individuals with DNAH11 variants. RESULTS: In this study, we identified seven novel variants in the DNAH11 gene in four asthenoteratozoospermia subjects. These variants led the absence of DNAH11 proteins and ultrastructure defects in sperm flagella, particularly affecting the outer dynein arms (ODAs) and adjacent structures. The levels of ODA protein DNAI2 and axoneme related proteins were down regulated, instead of inner dynein arms (IDA) proteins DNAH1 and DNAH6. Two out of four individuals with DNAH11 variants achieved clinical pregnancies through ICSI. The findings confirm the association between male infertility and bi-allelic deleterious variants in DNAH11, resulting in the aberrant assembly of sperm flagella and contributing to asthenoteratozoospermia. Importantly, ICSI emerges as an effective intervention for overcoming reproductive challenges caused by DNAH11 gene variants.

Maternal folic acid over-supplementation impairs cardiac function in mice offspring by inhibiting SOD1 expression.

BACKGROUND: Folic acid (FA) supplementation during pregnancy aims to protect foetal development. However, maternal over-supplementation of FA has been demonstrated to cause metabolic dysfunction and increase the risk of autism, retinoblastoma, and respiratory illness in the offspring. Moreover, FA supplementation reduces the risk of congenital heart disease. However, little is known about its possible adverse effects on cardiac health resulting from maternal over-supplementation. In this study, we assessed the detrimental effects of maternal FA over-supplementation on the cardiac health of the offspring. METHODS AND RESULTS: Eight-week-old C57BL/6J pregnant mice were randomly divided into control and over-supplemented groups. The offspring cardiac function was assessed using echocardiography. Cardiac fibrosis was assessed in the left ventricular myocardium by histological analysis. Proteomic, protein, RNA, and DNA methylation analyses were performed by liquid chromatography-tandem mass spectrometry, western blotting, real-time quantitative PCR, and bisulfite sequencing, respectively. We found that maternal periconceptional FA over-supplementation impaired cardiac function with the decreased left ventricular ejection fraction in the offspring. Biochemical indices and tissue staining further confirmed impaired cardiac function in offspring caused by maternal FA over-supplementation. The combined proteomic, RNA expression, and DNA methylation analyses suggested that key genes involved in cardiac function were inhibited at the transcriptional level possibly due to increased DNA methylation. Among these, superoxide dismutase 1 was downregulated, and reactive oxygen species (ROS) levels increased in the mouse heart. Inhibition of ROS generation using the antioxidant N-acetylcysteine rescued the impaired cardiac function resulting from maternal FA over-supplementation. CONCLUSIONS: Our study revealed that over-supplementation with FA during mouse pregnancy is detrimental to cardiac function with the decreased left ventricular ejection fraction in the offspring and provides insights into the mechanisms underlying the association between maternal FA status and health outcomes in the offspring.

Association of lifestyle and occupational exposure factors with human semen quality: a cross-sectional study of 1060 participants.

The incidence of male infertility (MI) is rising annually. However, the lifestyle and occupational exposure factors contributing to MI remain incompletely understood. This study explored the effects of self-reported lifestyle and occupational exposure factors on semen quality. Among 1060 subjects invited to participate, 826 were eligible. The participants' general characteristics, lifestyle, and occupational exposure factors were collected immediately before or after semen evaluation through an online questionnaire. Initially, univariate analysis was used to investigate the relationship between the abovementioned factors and semen quality. The results indicated significant associations between low semen quality and various factors, including age, BMI, infertility type and duration, abstinence time, semen and sperm parameters, smoking, alcohol consumption, irregular sleep habits, and frequent exposure to high temperatures and chemicals at work (p < 0.05). Then, multivariate analysis was conducted to identify factors independently associated with low semen quality. Adjustment for relevant confounders was achieved by including factors with a p-value < 0.25 from univariate analyses as covariates in the binomial and ordered logistic regression models. The results suggested that alcohol consumption was a positive factor for sperm concentration (odds ratio [OR] = 0.60; 95% confidence interval [CI] = 0.36-0.99; p = 0.045). The groups with a BMI ≥ 24 and <28 kg/m2 showed a significant decrease in sperm progressive motility when compared to the reference group (BMI < 24 kg/m2) (OR = 0.63; 95% CI = 0.46-0.87, p = 0.005). In addition, the groups that drank green tea <1 time/week (OR = 1.52, 95% CI = 1.05-2.2) and 1-4 times/week (OR = 1.61, 95% CI = 1.02-2.54) exhibited significantly increased sperm DFI values compared with the group that drank green tea 5-7 times/week. In conclusion, these findings underscore the importance of maintaining a normal weight and regularly consuming green tea for men.

Adenylate kinase phosphate energy shuttle underlies energetic communication in flagellar axonemes.

The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species. Enzymatic shuttles, particularly adenylate kinase (AK) and creatine kinase (CK), are pivotal in the efficient transfer of intracellular ATP, showing distinct tissue- and species-specificity. Here, the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups, of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates. Both AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male cohort. Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility. Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke (RS) of the axoneme. Examination of various human and mouse sperm samples with substructural damage, including the presence of multiple RS subunits, showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme. Using an ATP probe together with metabolomic analysis, it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme, and were concentrated at sites associated with energy consumption in the flagellum. These findings indicate a novel function for RS beyond its structural role, namely, the regulation of ATP transfer. In conclusion, the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.

Multibarrier-penetrating drug delivery systems for deep tumor therapy based on synergistic penetration strategy.

Nanotherapies, valued for their high efficacy and low toxicity, frequently serve as antitumor treatments, but do not readily penetrate deep into tumor tissues and cells. Here we developed an improved tumor-penetrating peptide (TPP)-based drug delivery system. Briefly, the established TPP iNGR was modified to generate a linear NGR peptide capable of transporting nanotherapeutic drugs into tumors through a CendR pathway-dependent, neuropilin-1 receptor-mediated process. Although TPPs have been reported to reach intended tumor targets, they often fail to penetrate cell membranes to deliver tumoricidal drugs to intracellular targets. We addressed this issue by harnessing cell penetrating peptide technology to develop a liposome-based multibarrier-penetrating delivery system (mbPDS) with improved synergistic drug penetration into deep tumor tissues and cells. The system incorporated doxorubicin-loaded liposomes coated with nona-arginine (R9) CPP and cyclic iNGR (CRNGRGPDC) molecules, yielding Lip-mbPDS. Lip-mbPDS tumor-targeting, tumor cell/tissue-penetrating and antitumor capabilities were assessed using CD13-positive human fibrosarcoma-derived cell (HT1080)-based in vitro and in vivo tumor models. Lip-mbPDS evaluation included three-dimensional layer-by-layer confocal laser scanning microscopy, cell internalization/toxicity assays, three-dimensional tumor spheroid-based penetration assays and antitumor efficacy assays conducted in an animal model. Lip-mbPDS provided enhanced synergistic drug penetration of multiple biointerfaces for potentially deep tumor therapeutic outcomes.

Multigenerational paternal obesity enhances the susceptibility to male subfertility in offspring via Wt1 N6-methyladenosine modification.

There is strong evidence that obesity is a risk factor for poor semen quality. However, the effects of multigenerational paternal obesity on the susceptibility to cadmium (a reproductive toxicant)-induced spermatogenesis disorders in offspring remain unknown. Here, we show that, in mice, spermatogenesis and retinoic acid levels become progressively lower as the number of generations exposed to a high-fat diet increase. Furthermore, exposing several generations of mice to a high fat diet results in a decrease in the expression of Wt1, a transcription factor upstream of the enzymes that synthesize retinoic acid. These effects can be rescued by injecting adeno-associated virus 9-Wt1 into the mouse testes of the offspring. Additionally, multigenerational paternal high-fat diet progressively increases METTL3 and Wt1 N6-methyladenosine levels in the testes of offspring mice. Mechanistically, treating the fathers with STM2457, a METTL3 inhibitor, restores obesity-reduced sperm count, and decreases Wt1 N6-methyladenosine level in the mouse testes of the offspring. A case-controlled study shows that human donors who are overweight or obese exhibit elevated N6-methyladenosine levels in sperm and decreased sperm concentration. Collectively, these results indicate that multigenerational paternal obesity enhances the susceptibility of the offspring to spermatogenesis disorders by increasing METTL3-mediated Wt1 N6-methyladenosine modification.

Adherence to a healthy sleep pattern and risk of urologic cancers: A large prospective cohort study.

OBJECTIVE: A variety of unhealthy sleep behaviors have been shown to be associated with an increased risk of urologic cancers. However, little is known about the association between the overall sleep patterns and urologic cancers. To prospectively investigate the associations between a healthy sleep pattern and the risks of urologic cancers, including bladder cancer (BCa) and renal cell carcinoma (RCC). METHODS: In this prospective cohort study, 377,144 participants free of cancer at baseline were recruited from the UK Biobank. Data on sleep behaviors were collected through questionnaires at recruitment. The incident urologic cancer cases were determined through linkage to national cancer and death registries. We established a healthy sleep score according to five sleep traits (sleep duration, chronotype, insomnia, snoring, and daytime sleepiness). Cox proportional hazard regression models were used to calculate the adjusted hazard ratios and 95% confidence intervals to assess the relationship between the healthy sleep score and the risk of urologic cancers. RESULTS: During a median of ≥9 years of follow-up, we identified 1986 incident urologic cancer cases, including 1272 BCa cases and 706 RCC cases. Compared with the participants with a poor sleep pattern (score of 0-2), the multivariable-adjusted hazard ratio and 95% confidence interval were 0.85 (0.75 to 0.96) for urologic cancers, 0.80 (0.68 to 0.93) for BCa, and 0.91 (0.74, 1.12) for RCC, respectively, for those with the healthier sleep pattern (score of 4-5). CONCLUSION: Our results indicate that a healthy sleep pattern is associated with lower risks of urologic cancers.

18F-labeled somatostatin analogs for somatostatin receptors (SSTRs) targeted PET imaging of neuroendocrine tumors (NETs).

PURPOSE: A novel 18F-radiolabeled somatostatin analogue, [Al18F]NODA-MPAA-HTA, was synthesized and evaluated for positron emission tomography (PET) imaging of Neuroendocrine tumors (NETs). [Al18F]NODA-MPAA-HTA was designed and synthesized by conjugating 18F nuclide with a modified KE108 peptide, a somatostatin analog with high affinity for all five subtypes of somatostatin receptors (SSTR 1-5), through coupling a bifunctional chelator (NODA) to target somatostatin receptor (SSTR) positive tumors. METHODS: The amino group of KE108 peptide, a SSTRs-targeting pharmacophore, was conjugated with the carboxyl group of NODA by a condensation reaction to obtain the labeling precursor of [Al18F]NODA-MPAA-HTA, in which its precursor was obtained through Fmoc solid-phase methods. A novel methodology for Al18F labeling of chelating agent-biomolecule conjugates was used to synthesize [Al18F]NODA-MPAA-HTA. In vitro stabilities of [Al18F]NODA-MPAA-HTA were evaluated by incubating it in saline or bovine serum for 2 h. Ex vivo biodistribution and in vivo imaging of [Al18F]NODA-MPAA-HTA were further investigated to evaluate its SSTRs targeting ability and feasibility for the diagnosis of NETs using PET imaging. RESULTS: [Al18F]NODA-MPAA-HTA was synthesized using a one-step 18F-AlF labeling procedure resulting in moderate radiochemical yield (60-80 %, non-decay corrected) and high radiochemical purity (>95 %). It exhibited good hydrophilicity and excellent stability in vitro, with a molar activity of 122 GBq/µmol. At 30 min and 60 min, the uptake of [Al18F] NODA-MPAA-HTA by HEK293-SSTR2 cells was 5.47 ± 0.97 %/105 cells and 12.11 ± 0.32 %/105 cells, respectively. The affinity of [Al18F]NODA-MPAA-HTA for SSTR2 was determined to be 8.77 ± 1.14 nM. In micro-PET imaging of HEK293-SSTR2 tumor-bearing mice, [Al18F]NODA-MPAA-HTA showed high tumor uptake of radioactivity and a high tumor-to-muscle ratio. Biodistribution results confirmed that radioactivity uptake in the tumor was significantly higher than that in the muscle by more than five-fold (P<0.001). Furthermore, the relatively low bone uptake of [Al18F]NODA-MPAA-HTA suggested that defluorination did not occur in vivo. These preliminary results provide experimental evidence for further study of Al18F-labeled somatostatin analogues as tumor probes for PET imaging of NETs. CONCLUSION: Fluorine-18 is widely used as a radionuclide for the production of radiopharmaceuticals for positron emission tomography (PET). Due to its short half-life (T1/2,109.8 min), its ease of production will facilitate the widespread dissemination of this radiopharmaceutical. A high-quality [Al18F]NODA-MPAA-HTA was synthesized with satisfactory yield. This radiopharmaceutical demonstrated higher tumor uptake and better tumor-to-muscle contrast, resulting to excellent image quality. These findings suggest that the novel 18F-labeled somatostatin analogue, [Al18F]NODA-MPAA-HTA, is a promising tool for PET imaging of NETs.

Three new cadinene-type sesquiterpenoids from the aerial parts of Ageratina adenophora.

Three new cadinene sesquiterpenoids 1-3, were isolated from the aerial sections of Ageratina adenophora using various chromatographic techniques. Their structures were characterised by comprehensive spectroscopic investigations (including 1D, 2D-NMR and HRMS), and single crystal X-ray diffraction. The cytotoxic activity of new compounds 1-3 were evaluated by testing in vitro tumour growth inhibitory rate against five human tumour cell lines, HL-60, A-549, SMMC-7721, MDA-MB-231, and SW480.

Endoscopic transsphenoidal approach in resection of intracranial clivus chondrosarcoma: A case report.

Intracranial primary chondrosarcomas are rare, accounting for <0.15% of all intracranial tumors, but exhibit a high risk of recurrence. Due to the rarity of this condition, it has proven difficult to establish efficacy-based treatment guidelines. The present study details a case of clivus chondrosarcoma exhibiting no recurrence following surgical resection using an endoscopic transsphenoidal approach and postoperative adjuvant radiotherapy. A 41-year-old female presented with primary symptoms of left eye esotropia, scotoma of the left nasal visual field and double vision. Preoperative cranial magnetic resonance imaging revealed a lesion on the clivus, which was initially diagnosed as chordoma. However, clivus chondrosarcoma was ultimately diagnosed based on intraoperative findings and postoperative histopathology. The tumor was totally resected and 25 doses of adjuvant radiotherapy with planning gross tumor volume (60 Gy) and planning clinical target volume (50 Gy) were administered for 5 weeks. The patient was discharged at 12 days post-surgery with no obvious postoperative complications. Over the 28-month follow-up period, there was no evidence of recurrence, which may be due to the successful use of combined gross total resection and adjuvant radiotherapy. Therefore, surgical resection using an endoscopic transsphenoidal approach and postoperative adjuvant radiotherapy is an effective method for treating intracranial clivus chondrosarcoma.

Development and validation of a kidney renal clear cell carcinoma prognostic model relying on pyroptosis-related LncRNAs-A multidimensional comprehensive bioinformatics exploration.

BACKGROUND: Renal cell carcinoma (RCC) is a malignant tumour that may develop in the kidney. RCC is one of the most common kinds of tumours of this sort, and its most common pathological subtype is kidney renal clear cell carcinoma (KIRC). However, the aetiology and pathogenesis of RCC still need to be clarified. Exploring the internal mechanism of RCC contributes to diagnosing and treating this disease. Pyroptosis is a critical process related to cell death. Recent research has shown that pyroptosis is a critical factor in the initiation and progression of tumour formation. Thus far, researchers have progressively uncovered evidence of the regulatory influence that long noncoding RNAs (lncRNAs) have on pyroptosis. METHODS: In this work, a comprehensive bioinformatics approach was used to produce a predictive model according to pyroptosis-interrelated lncRNAs for the purpose of predicting the overall survival and molecular immune specialties of patients diagnosed with KIRC. This model was verified from multiple perspectives. RESULTS: First, we discovered pyroptosis-associated lncRNAs in KIRC patients using the TCGA database and a Sankey diagram. Then, we developed and validated a KIRC patient risk model based on pyroptosis-related lncRNAs. We demonstrated the grouping power of PLnRM through PCA and used PLnRM to assess the tumour immune microenvironment and response to immunotherapy. Immunological and molecular traits of diverse PLnRM subgroups were evaluated, as were clinical KIRC patient characteristics and predictive risk models. On this basis, a predictive nomogram was developed and analyzed, and novel PLnRM candidate compounds were identified. Finally, we investigated possible medications used by KIRC patients. CONCLUSIONS: The results demonstrate that the model generated has significant value for KIRC in clinical practice.

Unusual 5/5 fused bicyclosesquiterpenoids from Eupatorium adenophorum.

The chemical analysis on the aerial sections of Eupatorium adenophorum Spreng. resulted in the identification of four unprecedented 5/5 fused bicyclosesquiterpenoids, eupatorid A (1), and its analogues named eupatorester A-C (2-4) using various chromatographic techniques. Their structures were unambiguously confirmed by detailed spectroscopic investigations (including 1D, 2D-NMR and HRMS), and single crystal X-ray diffraction. The anti-inflammatory activities, in vitro tumor growth inhibitory activities and antibacterial activities of these compounds were evaluated.

Novel cancer treatment paradigm targeting hypoxia-induced factor in conjunction with current therapies to overcome resistance.

Chemotherapy, radiotherapy, targeted therapy, and immunotherapy are established cancer treatment modalities that are widely used due to their demonstrated efficacy against tumors and favorable safety profiles or tolerability. Nevertheless, treatment resistance continues to be one of the most pressing unsolved conundrums in cancer treatment. Hypoxia-inducible factors (HIFs) are a family of transcription factors that regulate cellular responses to hypoxia by activating genes involved in various adaptations, including erythropoiesis, glucose metabolism, angiogenesis, cell proliferation, and apoptosis. Despite this critical function, overexpression of HIFs has been observed in numerous cancers, leading to resistance to therapy and disease progression. In recent years, much effort has been poured into developing innovative cancer treatments that target the HIF pathway. Combining HIF inhibitors with current cancer therapies to increase anti-tumor activity and diminish treatment resistance is one strategy for combating therapeutic resistance. This review focuses on how HIF inhibitors could be applied in conjunction with current cancer treatments, including those now being evaluated in clinical trials, to usher in a new era of cancer therapy.

[Corrigendum] Curcumin reverses benzidine-induced epithelial-mesenchymal transition via suppression of ERK5/AP-1 in SV-40 immortalized human urothelial cells.

Following the publication of the above article, an interested reader drew to the authors' attention that, for the Transwell invasion assays shown in Fig. 5D on p. 1326, the images selected for the '0 µM benzidine / 0 µM curcumin' and '0 µM benzidine / 1 µM curcumin' experiments were overlapping, such that these data appeared to have been derived from the same original source. After having consulted their original data, the authors have realized that the '0 µM benzidine / 1 µM curcumin' data panel was selected incorrectly. The revised version of Fig. 5, showing the correct data for the '0 µM benzidine / 1 µM curcumin' data panel in Fig. 5D, is shown on the next page. The authors regret that this error went unnoticed prior to the publication of this article, and thank the Editor of International Journal of Oncology for allowing them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they also apologize to the readership of the journal for any inconvenience caused.[International Journal of Oncology 50: 1321­1329, 2017; DOI: 10.3892/ijo.2017.3887].

Cigarette Smoke-Induced Gastric Cancer Cell Exosomes Affected the Fate of Surrounding Normal Cells via the Circ0000670/Wnt/ß-Catenin Axis.

Cigarette smoke is a major risk factor for gastric cancer. Exosomes are an important part of intercellular and intra-organ communication systems and can carry circRNA and other components to play a regulatory role in the occurrence and development of gastric cancer. However, it is unclear whether cigarette smoke can affect exosomes and exosomal circRNA to promote the development of gastric cancer. Exosomes secreted by cancer cells promote cancer development by affecting surrounding normal cells. Herein, we aimed to clarify whether the exosomes secreted by cigarette smoke-induced gastric cancer cells can promote the development of gastric cancer by affecting the surrounding gastric mucosal epithelial cells (GES-1). In the present study, we treated gastric cancer cells with cigarette smoke extract for 4 days and demonstrated that cigarette smoke promotes the stemness and EMT of gastric cancer cells and cigarette smoke-induced exosomes promote stemness gene expression, EMT processes and the proliferation of GES-1 cells. We further found that circ0000670 was up-regulated in tissues of gastric cancer patients with smoking history, cigarette smoke-induced gastric cancer cells and their exosomes. Functional assays showed that circ0000670 knockdown inhibited the promoting effects of cigarette smoke-induced exosomes on the stemness and EMT characteristic of GES-1 cells, whereas its overexpression had the opposite effect. In addition, exosomal circ0000670 was found to promote the development of gastric cancer by regulating the Wnt/ß-catenin pathway. Our findings indicated that exosomal circ0000670 promotes cigarette smoke-induced gastric cancer development, which might provide a new basis for the treatment of cigarette smoke-related gastric cancer.

The Signal Characteristics of Oil and Gas Pipeline Leakage Detection Based on Magneto-Mechanical Effects.

In order to solve the problem of the quantification of detection signals in the magnetic flux leakage (MFL) of defective in-service oil and gas pipelines, a non-uniform magnetic charge model was established based on magnetic effects. The distribution patterns of magnetic charges under different stresses were analyzed. The influences of the elastic load and plastic deformation on the characteristic values of MFL signals were quantitatively assessed. The experimental results showed that the magnetic charge density was large at the edges of the defect and small at the center, and approximately decreased linearly with increasing stress. The eigenvalues of the axial and radial components of the MFL signals were compared, and it was found that the eigenvalues of the radial component exhibited a larger decline rate and were more sensitive to stress. With the increase in the plastic deformation, the characteristic values of the MFL signals initially decreased and then increased, and there was an inflection point. The location of the inflection point was associated with the magnetostriction coefficient. Compared with the uniform magnetic charge model, the accuracy of the axial and radial components of the MFL signals in the elastic stage of the improved magnetic charge model rose by 17% and 16%, respectively. The accuracy of the axial and radial components of the MFL signals were elevated by 9.15% and 9%, respectively, in the plastic stage.

Fascia defect closure versus non-closure in minimal invasive direct inguinal hernia mesh repair: a systematic review and meta-analysis of real-world evidence.

PURPOSE: Laparoscopic and robotic inguinal hernia mesh repair are both common surgical procedures worldwide. Postoperative hernia recurrence and seroma formation are important concerns. In ventral hernia, primary defect closure in laparoscopic surgery reduces the recurrence rate. However, there is no synthetic evidence of direct inguinal hernia defect closure versus non-closure in minimal invasive surgery. Therefore, this study investigated the efficacy of defect closure in patients undergoing minimal invasive direct inguinal hernia mesh repair. METHODS: Eligible studies were identified through a search of PubMed, Embase, Cochrane Library, and CINAHL from their inception until March 2022. Studies examining defect closure in laparoscopic direct inguinal hernia repair were included, and a meta-analysis was performed using the random-effect model. Sensitivity analyses were performed by removing one study at a time. The primary outcomes were hernia recurrence and seroma formation. Acute and chronic postoperative pain, operation time, and length of hospital stay were the secondary outcomes. RESULTS: Five nonrandomized studies and one randomized controlled trial were included. Pooled analysis revealed defect closure might reduce the hernia recurrence rate (risk difference, - 0.02; 95% confidence interval [CI] - 0.04 to - 0.00; p = 0.02). The result of seroma formation (odds ratio, 0.49; 95% CI 0.17-1.46; p = 0.20) showed no significant difference. Moreover, no significant differences were observed in acute postoperative pain, chronic pain, length of hospital stay, and operation time. CONCLUSIONS: Our study indicated defect closure seems to be an option to reduce the direct inguinal hernia recurrence rate. No significant benefits were shown in seroma formation and other secondary outcomes. Our study was mostly based on nonrandomized studies and underestimated the effect of defect closure; thus, further high-quality studies are required to draw definitive conclusions.

Analgesic Effects of Regional Analgesic Techniques in Pediatric Inguinal Surgeries: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Various regional analgesic techniques have been used in pediatric inguinal surgery to facilitate postoperative recovery. However, each technique's relative performance was undetermined owing to the lack of quantitative analysis. METHODS: We systematically searched MEDLINE, Cochrane Library, EMBASE, and Web of Science for randomized controlled trials that compared regional analgesia in pediatric inguinal surgeries. After critical study screening and selection, a random-effects network meta-analysis was performed. The primary outcome was the time to the first rescue analgesic after surgery, and the secondary outcomes were the number of patients requiring rescue analgesics after surgery, postoperative pain scores, incidence of postoperative nausea and vomiting, and other adverse events. RESULTS: This network meta-analysis included 69 randomized controlled trials (4636 patients) that compared 10 regional analgesic techniques. Our study revealed that the quadratus lumborum and transversus abdominis plane blocks had the longest time to the first rescue analgesic after pediatric inguinal surgeries, by 7.7 hours (95% confidence interval [CI], 5.0-10.3) and 6.0 hours (95% CI, 3.9-8.2) when compared with the control group, respectively. In the subgroup involving only inguinal hernia repair, the quadratus lumborum block significantly prolonged the time to the first rescue analgesic than all other regional analgesics. In contrast, in the subgroup involving orchidopexies, only the caudal block significantly prolonged the time to the first rescue analgesic when compared with the control group (4.1 hours; 95% CI, 0.7-7.5). Wound infiltration and landmark-based ilioinguinal-iliohypogastric block had relatively poor analgesic effects than other regional analgesics. No serious adverse effects related to the regional analgesic techniques were reported in any of the included studies. CONCLUSIONS: The quadratus lumborum and transversus abdominis plane blocks had the longest time to the first rescue analgesic and the least rescue analgesic requirement for pediatric inguinal surgeries. Specifically, the quadratus lumborum block had the longest analgesic duration in inguinal hernia repair, and the caudal block was found to be the only regional analgesia that extended the time to the first rescue analgesic in pediatric orchidopexy. Most included randomized controlled trials had some concern or a high risk of bias, and future studies should focus on providing high-quality evidence to further clarify the analgesic effects of regional analgesia for pediatric inguinal surgeries.

Supramolecular catalytic nanomedicines based on coordination self-assembly of amino acids for cascade-activated and -amplified synergetic cancer therapy.

Simple biomolecule-based supramolecular nanomedicines hold great promise in cancer therapy, but their clinical translation is greatly hindered by low tumor-specificity and unsatisfactory antitumor performance. Herein, we developed an amino acid basedsupramolecular nanomedicine that could be co-activated by multiple stimuli in tumor tissue to trigger cascade catalytic reactions in situ for synergetic therapy. The supramolecular nanomedicine was developed based on a combination of coordination and hydrophobic noncovalent interactions among amphiphilic amino acids, glucose oxidase (GOx), copper ions, as well as doxorubicin (DOX)-camptothecin (CPT) prodrugs. The cascade reactions including the catalytic oxidation of glucose to generate H2O2, GSH reducing Cu2+ to Cu+, a Fenton-like reaction between H2O2 and Cu+ to produce hydroxyl radicals (˙OH), and ˙OH-triggered rapid release of dual parent drugs were specifically activated in tumor cells. With these cascade reactions, the catalytic-chemo synergetic therapy was realized for high-efficiency tumor suppression.