Mesoderm/mesenchyme homeobox l may promote tumor progression in human hepatocellular carcinoma.

BACKGROUND: The clinical response rate for molecularly targeted medications is limited despite significant advancements in molecularly targeted therapy for hepatocellular carcinoma (HCC). Therefore, it is necessary to find new and robust therapeutic targets for the treatment of HCC. Recent research has shown that mesoderm/mesenchyme homeobox gene 1 (Meox1) is closely associated with cancer progression. OBJECTIVES: The aim of this study was to evaluate the clinical relevance as well as biological function of Meox1 in HCC. MATERIAL AND METHODS: Meox1 protein expression level was identified through immunohistochemistry (IHC) examination of pathological tissues from 25 HCC patients. The aim of the analysis was to investigate the relationship between clinicopathological traits and Meox1 expression. Biological function assays of Meox1 in HCC, including proliferation, colony formation, migration, and invasion, were performed with Huh7 and Hep3B cells. RESULTS: In this study, Meox1 expression in HCC tissues was significantly higher (p < 0.05) compared to paracancerous tissues. Especially in HCC tissues of patients with cirrhosis, the level of Meox1 expression was significantly elevated when compared to HCC tissues of patients without cirrhosis (p < 0.05). High Meox1 expression was significantly associated with tumor-node-metastasis (TNM) stage (p < 0.05) and the Barcelona Clinic Liver Cancer (BCLC) stage (p < 0.05). Moreover, Meox1 silencing suppressed the proliferation, colony formation, migration, and invasion of Huh7 and Hep3B cells. CONCLUSIONS: Our data reveal that Meox1 may play a crucial role in the development of HCC, and given the function of Meox1 in proliferation and metastasis, targeting Meox1 may offer a promising approach for combined and adjuvant therapeutics of HCC.

Quantitative Flow Ratio-Derived Index of Microcirculatory Resistance as a Novel Tool to Identify Microcirculatory Function in Patients with Ischemia and No Obstructive Coronary Artery Disease.

BACKGROUND: Coronary microvascular disease (CMVD) is associated with adverse cardiovascular outcomes. However, there is no reliable and noninvasive quantitative diagnostic method available for CMVD. The use of a pressure wire to measure the index of microcirculatory resistance (IMR) is possible, but it has inevitable practical restrictions. We hypothesized that computation of the quantitative flow ratio could be used to predict CMVD with symptoms of ischemia and no obstructive coronary artery disease (INOCA). METHODS: We retrospectively assessed the diagnostic efficiency of the quantitative flow ratio-derived index of microcirculatory resistance (QMR) in 103 vessels from 66 patients and compared it with invasive IMR using the thermodilution technique. RESULTS: Patients were divided into the CMVD group (41/66, 62.1%) and non-CMVD group (25/66, 37.9%). Pressure wire IMR measurements were made in 103 coronary vessels, including 44 left descending arteries, 18 left circumflex arteries, and 41 right coronary arteries. ROC curve analysis showed a good diagnostic performance of QMR for all arteries (area under the curve = 0.820, 95% confidence interval 0.736-0.904, p < 0.001) in predicting microcirculatory function. The optimal cut-off for QMR to predict microcirculatory function was 266 (sensitivity: 82.9%, specificity: 72.6%, and diagnostic accuracy: 76.7%). CONCLUSION: QMR is a promising tool for the assessment of coronary microcirculation. The assessment of the IMR without the use of a pressure wire may enable more rapid, convenient, and cost-effective assessment of coronary microvascular function.

A TTC19 mutation associated with progressive movement disorders and peripheral neuropathy: Case report and systematic review.

BACKGROUND: Mitochondrial complex III (CIII) deficiency is an autosomal recessive disease characterized by symptoms such as ataxia, cognitive dysfunction, and spastic paraplegia. Multiple genes are associated with complex III defects. Among them, the mutation of TTC19 is a rare subtype. METHODS: We screened a Chinese boy with weakness of limbs and his non-consanguineous parents by whole exome sequencing and targeted sequencing. RESULTS: We report a Chinese boy diagnosed with mitochondrial complex III defect type 2 carrying a homozygous variant (c.719-732del, p.Leu240Serfs*17) of the TTC19 gene. According to the genotype analysis of his family members, this is an autosomal recessive inheritance. We provide his clinical manifestation. CONCLUSIONS: A new type of TTC19 mutation (c.719-732del, p.Leu240Serfs*17) was found, which enriched the TTC19 gene mutation spectrum and provided new data for elucidating the pathogenesis of CIII-deficient diseases.

Age-dependent changes in the gut microbiota and serum metabolome correlate with renal function and human aging.

Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.

Using the National Nosocomial Infections Surveillance risk index to determine risk factors associated with surgical site infections following gynecologic surgeries.

OBJECTIVES: We used the National Nosocomial Infections Surveillance (NNIS) risk index to determine risk factors associated with surgical site infections (SSIs) following gynecologic surgeries. MATERIAL AND METHODS: A retrospective study was conducted based on the medical records of 185 patients with SSIs, following gynecologic surgeries at a Grade A tertiary gynecologic and obstetric hospital in southwest China during September 2013-June 2021. RESULTS: Suspected risk factors associated with SSIs were: length of hospital stay, age, whether the patient had cancer, whether the patient had chemotherapy or high-dose antibiotic therapy before surgery, duration of surgery, amount of blood loss, and whether a blood transfusion was done. It was found that SSIs were more likely to occur in cancer patients with an NNIS risk index score of 1 and in patients with preoperative chemotherapy and an NNIS risk index score of 2. Among the patients with an NNIS risk index score of 2, the older the patient, the higher incidence of SSIs. CONCLUSIONS: Gynecologic surgery teams should pay more attention to the independent risk factors associated with SSIs determined by the NNIS risk index score to prevent SSIs following gynecologic surgeries, thus ensuring patient safety.

Recent advances of artificial intelligence in melanoma clinical practice.

Skin melanoma is a lethal cancer. The incidence of melanoma is increasing rapidly in all regions of the world. Despite significant breakthroughs in melanoma treatment in recent years, precise diagnosis of melanoma is still a challenge in some cases. Even specialized physicians may need time and effort to make accurate judgments. As artificial intelligence (AI) technology advances into medical practice, it may bring new solutions to this problem based on its efficiency, accuracy, and speed. This paper summarizes the recent progress of AI in melanoma-related applications, including melanoma diagnosis and classification, the discovery of new medication, guiding treatment, and prognostic assessment. The paper also compares the effectiveness of various algorithms in melanoma application and suggests future research directions for AI in melanoma clinical practice.

Vemurafenib induces a noncanonical senescence-associated secretory phenotype in melanoma cells which promotes vemurafenib resistance.

More than one half melanoma patients have BRAF gene mutation. BRAF inhibitor vemurafenib is an effective medication for these patients. However, acquired resistance is generally inevitable, the mechanisms of which are not fully understood. Cell senescence and senescence-associated secretory phenotype (SASP) are involved in extensive biological functions. This study was designed to explore the possible role of senescent cells in vemurafenib resistance. The results showed that vemurafenib treatment induced BRAF-mutant but not wild-type melanoma cells into senescence, as manifested by positive ß-galactosidase staining, cell cycle arrest, enlarged cellular morphology, and cyclin D1/p-Rb pathway inhibition. However, the senescent cells induced by vemurafenib (SenV) did not display DNA damage response, p53/p21 pathway activation, reactive oxygen species accumulation, decline of mitochondrial membrane potential, or secretion of canonical SASP cytokines. Instead, SenV released other cytokines, including CCL2, TIMP2, and NGFR, to protect normal melanoma cells from growth inhibition upon vemurafenib treatment. Xenograft experiments further confirmed that vemurafenib induced melanoma cells into senescence in vivo. The results suggest that vemurafenib can induce robust senescence in BRAFV600E melanoma cells, leading to the release of resistance-conferring cytokines. Both the senescent cells and the resistant cytokines could be potential targets for tackling vemurafenib resistance.

The role of the absence of Hyrtl's anastomosis in monochorionic pregnancy: Friend or foe?: A case report.

INTRODUCTION: Hyrtl's anastomosis, an intra-arterial shunt, plays a protective role when the placental territories supplied by the umbilical arteries are different in size. Its absence is associated with an increased risk of poor outcomes in singleton pregnancy. However, the literature and studies on the effect of absent Hyrtl's anastomosis in twin placentas are rare. CASE PRESENTATION: We present a case of a monochorionic diamniotic twin pregnancy complicated with type I selective fetal growth restriction (SFGR). Despite discordance in placental territory and cord insertion sites, the patient had an overall good pregnancy process, suggesting that the absence of Hyrtl's anastomosis may have played a benign role. CONCLUSIONS: The absence of Hyrtl's anastomosis in our case seemed to show a favorable effect, representing a finding of opposite effects in monochorionic placentas compared with singleton placentas.

Placental chorioangioma and pregnancy outcome: a ten-year retrospective study in a tertiary referral centre.

BACKGROUND: Placental chorioangioma is a rare disorder in pregnancy. We retrospectively reviewed the perinatal complications and long-term outcomes in pregnancies with placental chorioangioma and evaluated the factors affecting disease prognosis. METHODS: We reviewed pregnant women who delivered at our hospital in the past decade and whose diagnosis of placental chorioangioma was confirmed by pathological diagnosis. Information on maternal demographics, prenatal sonographic findings and perinatal outcomes was obtained by reviewing the medical records. In the latter part of the study, follow-up of children was conducted by phone interview. RESULTS: In the 10 years from August 2008 to December 2018, 175 cases(0.17%) were identified as placental chorioangioma histologically and 44(0.04%) of them were large chorioangiomas. Nearly one-third of cases with large chorioangiomas were associated with severe maternal and fetal complications or required prenatal intervention. Although one-fifth of fetuses/newborns complicated with large chorioangiomas were lost perinatally, the long-term prognosis for surviving fetuses was generally good. Further statistical analysis revealed that tumor size and location affect prognosis. CONCLUSION: Placental chorioangioma may cause an unfavorable perinatal outcome. Regular ultrasound monitoring can provide the tumor characteristics which can be referred to for predicting the tendency of those complications and indicate when intervention may be necessary. It is not clear which factors lead to complications with fetal damage as the main manifestation or polyhydramnios as the main manifestation.

Association of Tirofiban With Functional Outcomes After Thrombectomy in Acute Ischemic Stroke Due to Intracranial Atherosclerotic Disease.

BACKGROUND AND OBJECTIVE: To investigate the efficacy and safety of IV infusion of tirofiban before endovascular thrombectomy for patients with large vessel occlusion due to intracranial atherosclerotic disease. The secondary objective was to identify potential mediators for the clinical effect of tirofiban. METHODS: Post hoc exploratory analysis of the Endovascular Treatment With versus Without Tirofiban for Patients with Large Vessel Occlusion Stroke (RESCUE BT) trial, which was a randomized, double-blinded, placebo-controlled trial at 55 centers in China from October 2018 to October 2021. Patients with occlusion of the internal carotid artery or middle cerebral artery due to intracranial atherosclerosis were included. The primary efficacy outcome was the proportion of patients achieving functional independence (defined as modified Rankin scale 0-2) at 90 days. Binary logistic regression and causal mediation analyses were used to estimate the treatment effect of tirofiban and the potential mediators. RESULTS: This study included 435 patients, of whom 71.5% were men. The median age was 65 (interquartile range [IQR] 56-72) years, with a median NIH Stroke Scale of 14 (IQR 10-19). Patients in the tirofiban group had higher rates of functional independence at 90 days than patients in the placebo group (adjusted odds ratio 1.68; 95% CI 1.11-2.56, p = 0.02) without an increased risk of mortality or symptomatic intracranial hemorrhage. Tirofiban was associated with fewer thrombectomy passes (median [IQR] 1 [1-2] vs 1 [1-2], p = 0.004), which was an independent predictor of functional independence. Mediation analysis showed tirofiban-reduced thrombectomy passes explained 20.0% (95% CI 4.1%-76.0%) of the effect of tirofiban on functional independence. DISCUSSION: In this post hoc analysis of the RESCUE BT trial, tirofiban was an effective and well-tolerated adjuvant medication of endovascular thrombectomy for patients with large vessel occlusion due to intracranial atherosclerosis. These findings need to be confirmed in future trials. TRIAL REGISTRATION INFORMATION: The RESCUE BT trial was registered on the Chinese Clinical Trial Registry: chictr.org.cn, ChiCTR-INR-17014167. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tirofiban plus endovascular therapy improves 90-day outcome for patients with large vessel occlusion due to intracranial atherosclerosis.

Long non-coding RNA BC002811 Promotes Gastric Cancer Metastasis by Regulating SOX2 Binding to the PTEN Promoter.

There is increasing evidence that long non-coding RNAs (lncRNAs) are involved in the pathogenesis and progression of gastric cancer (GC), however, the underlying mechanisms remain poorly understood. In this study, we identified lncRNA BC002811 as a critical regulator of GC development and progression. BC002811 was upregulated in GC tissues and cell lines, and that high expression of BC002811 was indicative of a reduction in overall survival of GC patients. Our research reveals that BC002811 promoted GC cell proliferation, migration, invasion, and inhibition of apoptosis in vitro, as well as accelerated tumor growth and metastasis in vivo. We also found that BC002811 upregulated MMP2 and MMP9 and promoted GC cell metastasis partially through downregulating PTEN expression. BC002811 may act as a molecular decoy for the transcription factor SOX2, thereby inhibiting the transcription of PTEN by blocking SOX2 binding to the PTEN promoter. Our study advances the understanding of the role of BC002811 in the pathogenesis of GC and provides new molecular targets for therapeutic intervention against GC metastasis.

A natural carotenoid crocin exerts antidepressant action by promoting adult hippocampal neurogenesis through Wnt/ß-catenin signaling.

INTRODUCTION: Adult hippocampal neurogenesis (AHN) is acknowledged to play a critical role in depression. Emerging evidence suggests that the Wnt/ß-catenin pathway can modulate hippocampal neurogenesis. Crocin, a natural carotenoid, possesses antidepressant property. Yet, how it affects neurogenesis and exerts antidepressant response remains unknown. OBJECTIVE: To explore the role of AHN and Wnt/ß-catenin in the antidepressant action of crocin. METHODS: Depressive-related behaviors, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and sexual behaviors were performed following crocin treatment. Neurogenesis was characterized via immunohistochemistry, immunofluorescence, Golgi staining and electrophysiology approach. Wnt/ß-catenin signaling was examined with western blot analysis. The role of AHN Wnt/ß-catenin cascade in crocin's antidepressant response was assessed by conditional removal of glial fibrillary acidic protein (GFAP)-expressing newborn neural cells, temozolomide administration, microinfusion of Dkk1 or viral-mediated shRNA of Wnt3a. RESULTS: Crocin decreased the immobility duration in TST and FST without impairing the performance in sexual behaviors. Crocin boosted the proliferation and differentiation of progenitors, and promoted dendritic maturation and functional integration of hippocampal newborn neurons. Conditional removal of GFAP-expressing neural cells or temozolomide administration impaired the antidepressant response of crocin. Additionally, Wnt/ß-catenin signaling was promoted following crocin treatment. In chronic unpredictable mild stress (CUMS) murine model, crocin treatment displayed antidepressant response in SPT, FST and TST, and restored the neurogenesis levels and Wnt/ß-catenin signaling impaired by CUMS. Infusion of Dickkopf-1 (DKK1) or knockdown of Wnt3a in the hippocampus impaired the antidepressant response of crocin. CONCLUSION: Crocin exerted antidepressant response, which was dependent on enhancement of AHN and activation of the Wnt/ß-catenin pathway.

Generation of a human iPSC line (CIBi013-A) from a patient with young-onset Parkinson's disease carrying a novel homozygous PARK7 (DJ-1) mutation.

Mutations in PARK7 and the resulting alterations in its production protein (DJ-1) are tightly associated with Parkinson's disease. We generated a human induced pluripotent stem cell (iPSC) line (CIBi013-A) from a patient with young-onset Parkinson's disease (YOPD) who carried a novel homozygous PARK7 (DJ-1) mutation (chr1:8037723, c.334C>G). The generated iPSCs will be used for investigating phenotype and underlying molecular mechanisms in patient-derived cells.

Generation of a human iPSC line (CIBi014-A) from a patient with Parkinson's disease carrying a novel heterozygotic PARK8 (LRRK2) mutation.

Leucine-rich repeat kinase 2 (LRRK2), also known as Dardarin (derived from the Basque word "dardara," meaning tremor), is a protein kinase encoded by the PARK8 gene. This protein is mainly distributed in the cytoplasm; however, it is also present in the mitochondrial outer membrane. Mutations in the LRRK2 protein cause Parkinson's disease (PD). We generated a human induced pluripotent stem cell (iPSC) line (CIBi014-A) expressing pluripotency markers. This cell line exhibited a normal karyotype and could be differentiated into three germ layers in vitro. This line will be valuable for investigating the mechanism underlying PD and identifying potential therapeutic targets.

Circular RNA hsa_circ_0003574 as a biomarker for prediction and diagnosis of ischemic stroke caused by intracranial atherosclerotic stenosis.

Background: Intracranial atherosclerotic stenosis (ICAS) is a common cause of first and recurrent ischemic stroke worldwide. Circular RNAs (circRNA)s have been recently suggested as candidate biomarkers in diagnosing and prognosis of ischemic stroke. A few circRNAs even serve as therapeutic targets that improves neurological function after ischemic stroke. However, the roles of circRNAs in ICAS caused ischemic stroke (ICAS-stroke) have not been fully understood. Therefore, in this study, we attempted to find some clues by investigating the different expression profiles of circRNAs between patients diagnosed with ICAS-stroke and normal control (NC)s. Methods: The OE Biotech Human ceRNA Microarray 4 × 180 K (47, 899 probes) screened circRNAs differentially expressed in peripheral blood in a discovery cohort (5 NCs versus five patients with ICAS-stroke). Afterwards, a validation cohort (31 NCs versus 48 patients with ICAS-stroke) was performed by quantitative polymerase chain reaction (qPCR). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and CircRNA-microRNA-mRNA interaction network was performed to identify potential interactions with microRNAs and pathway-deregulated circRNAs. Results: There were 244 circRNAs differentially expressed in patients diagnosed with ICAS-stroke compared with NCs [fold change (FC) ≥ 2.0 and p-value<0.05]. Among the 244 circRNAs, 5 circRNAs (hsa_circ_0003574, hsa_circ_0010509, hsa_circ_0026628, hsa_circ_0074057, hsa_circ_0016993) were selected for following verification by qPCR. Only hsa_circRNA_0003574 was significantly upregulated in patients than in NCs. GO analysis indicated that predicted target genes involved various biological processes, cellular components, and molecular functions. KEGG analysis showed that many genes were enriched within the arginine and proline metabolism, pyrimidine metabolism, arginine and proline metabolism, lysosome, cytokine-cytokine receptor interaction, and RNA transport. The circRNA-miRNA-mRNA network analysis show the miRNAs that has_circ_0003574 likely interacts with. Conclusion: We observed that hsa_circRNA_0003574 is upregulated in patients with ICAS-stroke compared with NCs, indicating it may be a potential novel biomarker and therapeutic target for ICAS-stroke. In addition, we analyzed the laboratory results and found that homocysteine and glycosylated hemoglobin were elevated among ICAS-stroke patients. The relationship between hsa_circRNA_0003574 and these parameters requires further investigation.

Individual treatment strategy for single urethrocutaneous fistula after hypospadias repair: a retrospective cohort study.

Background: Urethrocutaneous fistula (UCF) remains the most common complication after hypospadias repair, and the recurrence rate of UCF is still high if the surgical techniques is not chosen properly, which called for better approaches to this problem. UCF presents different clinical characteristics due to their different locations and sizes, therefore we retrospectively analyzed the effects of different surgical techniques on single UCF after hypospadias repair in order to reduce the recurrence rates of UCF. Methods: A total of 602 patients diagnosed with UCF after hypospadias repair from January 2014 to December 2021 were enrolled. Baseline clinical characteristics such as age of patients, UCF location, size, surgical techniques were recorded. Patients were followed up in the outpatient clinic. The recurrence of UCF was defined as outcomes. Patients were divided according to the location of the UCF into a coronal UCF group and a non-coronal UCF group, which was then further classified according to the diameter of the UCF. The surgical technique and the recurrence rate of different types of UCF were analyzed and summarized. Results: A total of 425 patients satisfied the inclusion criteria and 71 patients (16.7%) had recurrent UCF. Five surgical techniques were used to repair the UCF, namely tubularized incised plate (TIP) urethroplasty, Mathieu urethroplasty, double ligation, simple classical closure and trap-door procedure. The recurrence rate was 24.1%, 14.3%, 15.1%, 16.7%, and 22.2%, respectively. TIP or Mathieu urethroplasty is recommended for patients with coronal UCF with glans dehiscence or patients with coronal UCF diameter ≥4 mm without glans dehiscence. In patients with coronal UCF without glans dehiscence, double ligation is recommended for small UCF with diameter <2 mm, and simple classical closure is recommended for UCF with diameter 2-<4 mm. In patients with non-coronal UCF, double ligation is recommended for UCF with diameter <3 mm, and simple classical closure is recommended for UCF with diameter ≥3 mm. Conclusions: Single UCF can be classified according to the location and size of the UCF. Different types of UCF should be treated with more appropriate individualized strategies, which can effectively reduce the recurrence rate of UCF.

Guanxin V attenuates myocardial ischaemia reperfusion injury through regulating iron homeostasis.

CONTEXT: Guanxin V (GX), a traditional Chinese medicine formula, is safe and effective in the treatment of coronary artery disease. However, its protective effect on myocardial ischaemia reperfusion injury (MIRI) is unclear. OBJECTIVE: To investigate the cardioprotective effect of GX on MIRI and explore the potential mechanism. MATERIALS AND METHODS: Sprague-Dawley male rats were divided into Sham, MIRI and MIRI + GX groups. GX (6 g/kg) was administered to rats via intragastric administration for seven days before ischaemia reperfusion (IR) surgery. The infarct size, histopathology, serum enzyme activities, ultrastructure of the cardiac mitochondria were assessed. H9c2 cells were pre-treated with GX (0.5 mg/mL), and then exposed to hypoxia/reoxygenation (HR). The cell viability and LDH levels were measured. Network pharmacology was conducted to predict the potential mechanism. The related targets of GX were predicted using the TCMSP database, DrugBank database, etc. Finally, pharmacological experiments were used to validate the predicted results. RESULTS: In vivo, GX significantly reduced the myocardial infarct size from 56.33% to 17.18%, decreased the levels of AST (239.32 vs. 369.18 U/L), CK-MB (1324.61 vs. 2066.47 U/L) and LDH (1245.26 vs. 1969.62 U/L), and reduced mitochondrial damage. In vitro, GX significantly increased H9c2 cell viability (IC50 = 3.913 mg/mL) and inhibited the release of LDH (207.35 vs. 314.33). In addition, GX could maintain iron homeostasis and reduce oxidative stress level by regulating iron metabolism-associated proteins. CONCLUSIONS: GX can attenuate MIRI via regulating iron homeostasis, indicating that GX may act as a potential candidate for the treatment of MIRI.

Pregnancy and delivery after augmentation cystoplasty: A case report and review of literature.

BACKGROUND: Augmentation cystoplasty, first described by Mikulicz in 1899 involves segments of bowel, stomach or mega-ureter to increase bladder capacity in those with inadequate bladder function or lack of detrusor compliance. The most widely used bowel segment is a detubularised patch of ileum. When ileum is not suitable for augmentation, sigmoid colon is the alternative. However, only eight pregnancies after sigmoidocystoplasty have been reported without detail and clinicians may be uncertain about the effects of sigmoidocystoplasty on reproductive health and pregnancy. CASE SUMMARY: We followed the patient from gestational week 32+3 until 6 wk after delivery. During pregnancy, our patient suffered urinary tract infection twice and had to undergo percutaneous nephrostomy drainage due to progressive hydronephrosis. Despite a dense adhesion between the uterus and neobladder, we were able to deliver a healthy baby by cesarian section in the presence of the attending urologist. CONCLUSION: Augmentation cystoplasty-afflicted women can have a healthy reproductive life. Certain perioperative measures may be advisable to avoid serious surgical complications.

Synthesis of multi-branched Au nanocomposites with distinct plasmon resonance in NIR-II window and controlled CRISPR-Cas9 delivery for synergistic gene-photothermal therapy.

Clinical implementation of photothermal therapy (PTT) is mainly hampered by limited tissue penetration, undesirable thermal damage to normal tissues, and thermotolerence induced by heat shock proteins (HSPs). To overcome these obstacles, we constructed a novel gene-photothermal synergistic therapeutic nanoplatform composed of a multi-branched Au nanooctopus (AuNO) core and mesoporous polydopamine (mPDA) shell, followed by CRISPR-Cas9 ribonucleoprotein (RNP) loading and then polyethylene glycol-folic acid (PEG-FA) coating. AuNO was simply synthesized by adjusting the ratio of cetyltrimethylammonium chloride (CTAC) and cetyltrimethylammonium bromide (CTAB), which showed significant localized surface plasmon resonances in the NIR-II window, and exhibited an excellent tissue penetration capability and high photothermal conversion efficiency (PCE, 47.68%). Even, the PCE could be further increased to 66.17% by mPDA coating. Furthermore, the sequential modification of AuNO@mPDA using RNP and PEG-FA can down-regulate HSP90α expression at tumor sites, enhance apoptosis and reduce the heat resistance of cancer cells. The synergistic effect of enhanced photothermal capacity and reduced thermoresistance addressed the multiple limitations of PTT, and presented excellent in vitro and in vivo antitumor efficacy, having great potential for the clinical application of PTT.

Enhanced ROS-Boosted Phototherapy against Pancreatic Cancer via Nrf2-Mediated Stress-Defense Pathway Suppression and Ferroptosis Induction.

In situ oxygen generation is the most common strategy to boost reactive oxygen species (ROS) for enhancing the efficacy of phototherapy in cancer, including photodynamic therapy (PDT) and photothermal therapy (PTT). However, hyperoxidation or hyperthermia often triggers stress-defense pathways and promotes tumor cell survival, thus severely limiting the therapeutic efficacy. To overcome the tumor hypoxia and thermal resistance existing in phototherapy, we constructed a self-synergistic nanoplatform for tumors by incorporating brusatol, a nuclear factor erythroid 2-related factor (Nrf2) inhibitor, into the silica nanonetwork. It was then sequentially decorated with MnO2 and the photosensitizer chlorin e6 (Ce6) and then coated with poly(ethylene glycol)-folate (PEG-FA)-functionalized polydopamine (PDA) (designated as brusatol/silica@MnO2/Ce6@PDA-PEG-FA). As an oxygen generator, MnO2 can promote ROS production, which not only directly enhances Ce6-mediated PDT but also strengthens PDA-mediated PTT by attacking heat shock proteins (HSPs). Particularly, brusatol could efficiently inhibit the activation of Nrf2 defense pathway under hyperoxidation and hyperthermia and cause glutathione peroxidase 4 (GPX4) and ferritin heavy chain (FTH) inactivation, thereby inducing ferroptosis and ultimately enhancing the phototherapeutic effects. By exploiting these features, brusatol/silica@MnO2/Ce6@PDA-PEG-FA exhibited excellent antitumor efficacy with enhanced PDT and PTT both in in vitro and in vivo studies. Overall, our work highlights a promising strategy against hypoxia- and hyperthermia-associated resistance in phototherapy via suppressing stress-defense system and inducing ferroptosis.