Three-dimensional laser micromachining system with integrated sub-100†nm resolution in-situ measurement.

In this study, a three-dimensional (3D) laser micromachining system with an integrated sub-100 nm resolution in-situ measurement system was proposed. The system used the same femtosecond laser source for in-situ measurement and machining, avoiding errors between the measurement and the machining positions. It could measure the profile of surfaces with an inclination angle of less than 10°, and the measurement resolution was greater than 100 nm. Consequently, the precise and stable movement of the laser focus could be controlled, enabling highly stable 3D micromachining. The results showed that needed patterns could be machined on continuous surfaces using the proposed system. The proposed machining system is of great significance for broadening the application scenarios of laser machining.

Paucatalinone A from Paulownia Catalpifolia Gong Tong Elicits mitochondrial-mediated cancer cell death to combat osteosarcoma.

As the global cancer burden escalates, the search for alternative therapies becomes increasingly vital. Natural products, particularly plant-derived compounds, have emerged as promising alternatives to conventional cancer treatments due to their diverse bioactivities and favorable biosafety profiles. Here, we investigate Paucatalinone A, a newly discovered geranylated flavanone derived from the fruit of Paulownia Catalpifolia Gong Tong, notable for its significant anti-cancer properties. We revealed the capability of Paucatalinone A to induce apoptosis in osteosarcoma cells and deciphered its underlying mechanisms. Our findings demonstrate that Paucatalinone A substantially augments apoptosis, inhibits cell proliferation, and demonstrates a pronounced anti-tumor effect in a murine model of osteosarcoma. Mechanistically, Paucatalinone A disrupts calcium homeostasis and exacerbates intracellular reactive oxygen species accumulation, leading to mitochondrial impairment, cytoskeletal collapse, and caspase-dependent apoptotic cell death. This study underscores the potential of Paucatalinone A in initiating apoptosis in cancer cells and highlights the therapeutic efficacy of plant-derived agents in treating osteosarcoma, offering a viable approach for managing other intractable cancers.

Efficacy of laparoscopic pyeloplasty for pediatric hydronephrosis caused by symptomatic versus asymptomatic endogenous ureteropelvic junction obstruction: a retrospective analysis.

OBJECTIVE: To retrospectively compare the differences in the surgical efficacy and prognosis of laparoscopic pyeloplasty for hydronephrosis caused by symptomatic versus asymptomatic ureteropelvic junction obstruction (UPJO) in children and determine whether clinical symptoms affect the surgical outcome and prognosis. METHODS: Children who underwent laparoscopic pyeloplasty in our hospital from January 2018 to December 2022 were retrospectively analyzed. The children were divided into symptomatic and asymptomatic groups according to their main symptoms. The primary outcomes were the surgical success rate, change in renal parenchymal thickness, and change in renal pelvis anteroposterior diameter. The secondary outcomes were postoperative complications, reoperation rate, operative duration, intraoperative blood loss, and drainage tube indwelling time. RESULTS: In total, 224 children with UPJO were enrolled; 148 (66.1%) were symptomatic and 76 (33.9%) were asymptomatic. The symptomatic group showed a significantly greater mean change in renal parenchymal thickness, significantly higher surgical success rate, and significantly lower postoperative complication rate. CONCLUSIONS: In the present study, asymptomatic children had a lower surgical success rate, less postoperative imaging improvement, and more postoperative complications than symptomatic children. The presence or absence of clinical symptoms may affect the surgical outcome and prognosis.

Risk factors for Hirschsprung disease-associated enterocolitis: a systematic review and meta-analysis.

BACKGROUND: The incidence of Hirschsprung disease (HSCR) is nearly 1/5000 and patients with HSCR are usually treated through surgical intervention. Hirschsprung disease-associated enterocolitis (HAEC) is a complication of HSCR with the highest morbidity and mortality in patients. The evidence on the risk factors for HAEC remains inconclusive to date. METHODS: Four English databases and four Chinese databases were searched for relevant studies published until May 2022. The search retrieved 53 relevant studies. The retrieved studies were scored on the Newcastle-Ottawa Scale by three researchers. Revman 5.4 software was employed for data synthesis and analysis. Stata 16 software was employed for sensitivity analysis and bias analysis. RESULTS: A total of 53 articles were retrieved from the database search, which included 10 012 cases of HSCR and 2310 cases of HAEC. The systematic analysis revealed anastomotic stenosis or fistula [ I2 =66%, risk ratio (RR)=1.90, 95% CI 1.34-2.68, P <0.001], preoperative enterocolitis ( I2 =55%, RR=2.07, 95% CI 1.71-2.51, P <0.001), preoperative malnutrition ( I2 =0%, RR=1.96, 95% CI 1.52-2.53, P <0.001), preoperative respiratory infection or pneumonia ( I2 =0%, RR=2.37, 95% CI 1.91-2.93, P <0.001), postoperative ileus ( I2 =17%, RR=2.41, 95% CI 2.02-2.87, P <0.001), length of ganglionless segment greater than 30 cm ( I2 =0%, RR=3.64, 95% CI 2.43-5.48, P <0.001), preoperative hypoproteinemia ( I2 =0%, RR=1.91, 95% CI 1.44-2.54, P <0.001), and Down syndrome ( I2 =29%, RR=1.65, 95% CI 1.32-2.07, P <0.001) as the risk factors for postoperative HAEC. Short-segment HSCR ( I2 =46%, RR=0.62, 95% CI 0.54-0.71, P <0.001) and transanal operation ( I2 =78%, RR=0.56, 95% CI 0.33-0.96, P =0.03) were revealed as the protective factors against postoperative HAEC. Preoperative malnutrition ( I2 =35 % , RR=5.33, 95% CI 2.68-10.60, P <0.001), preoperative hypoproteinemia ( I2 =20%, RR=4.17, 95% CI 1.91-9.12, P <0.001), preoperative enterocolitis ( I2 =45%, RR=3.51, 95% CI 2.54-4.84, P <0.001), and preoperative respiratory infection or pneumonia ( I2 =0%, RR=7.20, 95% CI 4.00-12.94, P <0.001) were revealed as the risk factors for recurrent HAEC, while short-segment HSCR ( I2 =0%, RR=0.40, 95% CI 0.21-0.76, P =0.005) was revealed as a protective factor against recurrent HAEC. CONCLUSION: The present review delineated the multiple risk factors for HAEC, which could assist in preventing the development of HAEC.

Laser defined and driven bio-inspired soft robots toward complex motion control.

The design and actuation of soft robots are targeted at extreme motion control as well as high functionalization. In spite of robot construction optimized by bio-concepts, its motion system is still hindered by multiple actuator assembly and reprogrammable control for complex motions. Herein, our recent work is summarized and an all-light solution is proposed and demonstrated using graphene-oxide-based soft robots. It will be shown that, with a highly localized light field, lasers can define actuators precisely to form "joints" and facilitate efficient energy storage and release to realize genuine complex motions.

A single-center study of thoracoscopic surgery in the treatment of pediatric mediastinal neurogenic tumors.

OBJECTIVE: To study the feasibility, safety, and efficacy of thoracoscopic surgery in the treatment of pediatric mediastinal neurogenic tumors, and summarize the treatment experiences and surgical skills. METHODS: A single-center retrospective analysis of 37 patients with pediatric mediastinal neurogenic tumors was conducted. Clinical charactersistics and postoperative complications were all analyzed. RESULTS: All the operations were successfully completed. There was no statistically significant difference in tumor diameter between the two groups (p > 0.05). The open surgery group had an average operation time of 96.5 ± 32.38 min, while the thoracoscopic surgery group had an average operation time of 78.3 ± 24.51 min (p < 0.05). The thoracoscopic surgery group had significantly lower intraoperative blood loss than the open surgery group (p < 0.05). In addition, the duration of the postoperative thoracic drainage tube was 5.43 ± 0.76 days in the open surgery group, which was longer than the 2.38 ± 0.87 days in the thoracoscopic surgery group (p < 0.05). Furthermore, the postoperative length of hospital stay was an average of 10.23 ± 1.43 days for the open surgery group, longer than for the thoracoscopic surgery group (4.36 ± 0.87 days) (p < 0.05). CONCLUSIONS: Thoracoscopic surgery has several advantages in the treatment of pediatric mediastinal neurogenic tumors and is worthy of clinical popularization and application. For giant mediastinal malignant neurogenic tumors, puncture biopsy and adjuvant chemotherapy can be performed before surgery to lessen the tumor volume and enlarge the operation space, which would reduce bleeding and complications.

Effect of Shengmai Yin on Epithelial-Mesenchymal Transition of Nasopharyngeal Carcinoma Radioresistant Cells.

OBJECTIVE: To investigate the mechanism by which Chinese medicine Shengmai Yin (SMY) reverses epithelial-mesenchymal transition (EMT) through lipocalin-2 (LCN2) in nasopharyngeal carcinoma (NPC) cells CNE-2R. METHODS: Morphological changes in EMT in CNE-2R cells were observed under a microscope, and the expressions of EMT markers were detected using quantitative real-time PCR (RT-qPCR) and Western blot assays. Through the Gene Expression Omnibus dataset and text mining, LCN2 was found to be highly related to radiation resistance and EMT in NPC. The expressions of LCN2 and EMT markers following SMY treatment (50 and 100 µ g/mL) were detected by RT-qPCR and Western blot assays in vitro. Cell proliferation, migration, and invasion abilities were measured using colony formation, wound healing, and transwell invasion assays, respectively. The inhibitory effect of SMY in vivo was determined by observing a zebrafish xenograft model with a fluorescent label. RESULTS: The CNE-2R cells showed EMT transition and high expression of LCN2, and the use of SMY (5, 10 and 20 µ g/mL) reduced the expression of LCN2 and reversed the EMT in the CNE-2R cells. Compared to that of the CNE-2R group, the proliferation, migration, and invasion abilities of SMY high-concentration group were weakened (P<0.05). Moreover, SMY mediated tumor growth and metastasis in a dose-dependent manner in a zebrafish xenograft model, which was consistent with the in vitro results. CONCLUSIONS: SMY can reverse the EMT process of CNE-2R cells, which may be related to its inhibition of LCN2 expression. Therefore, LCN2 may be a potential diagnostic marker and therapeutic target in patients with NPC.

Traditional Chinese Medicine: A Class of Potentially Reliable Epigenetic Drugs.

Epigenetic modification, especially DNA methylation, plays a nonnegligible role in the occurrence and development of tumors. Increasing studies are indicating that traditional Chinese medicine (TCM) plays a considerable anti-tumor role by regulating the process of DNA methylation modification. Studies on TCM regulating DNA methylation modification mostly focus on the whole genome and abnormal methylation status by active ingredients or single compounds and Chinese herb formula (CHF). The balance and overall concept of TCM theory coincides with the balance of DNA methylation modification in the tumor environment. Regardless of how TCM modulates epigenetics in tumor, it has been shown to bet a class of potentially reliable epigenetic drug.

Short-Term Outcomes of Herbert Screw Fixation for Isolated Olecranon Fractures in Children: A Single-Institution Retrospective Study.

Background: The aim of this study was to assess the clinical and radiological outcomes of closed reduction with percutaneous Herbert screw fixation in children with isolated olecranon fractures. Methods: We retrospectively reviewed the records of children treated at our center for isolated olecranon fractures (Mayo type IIA) with closed reduction and percutaneous Herbert screw fixation. The related indices and data of the group were collected for comparative analysis after an average follow-up of 6-8 months. The Herbert screws were removed by a second operation. Results: Overall, 14 patients with an average age at the time of injury of 11.36 (range 10-14) years were included. All patients had good radiological and clinical outcomes at 6-8 months postoperatively; all had normal elbow ranges of motion and showed complete bone healing on radiographs. There were no foreign body irritation, implant migration, or osteoarthritis cases. Premature epiphyseal closure was noted in six patients. The average QuickDASH score was 1.58. Conclusions: Fixation of olecranon fractures with Herbert screws is a safe and easy method in young patients, leading to good functional and radiological results. Nonetheless, determination of the effects of this treatment method on the olecranon ossification center requires long-term follow-up.

6'-O-Galloylpaeoniflorin Exerts Inhibitory Bioactivities in Human Neuroblastoma Cells via Modulating AMPK/miR-489/XIAP Pathway.

Although therapies against neuroblastoma (NBM) have advanced, the patients still suffer from poor prognoses due to distal metastasis or the occurrence of multidrug resistance. Accumulating evidence has proved that chemicals derived from natural products possess potent anti-NBM properties or can be used as adjuvants for chemotherapy. In the present study, we demonstrated that 6'-O-galloylpaeoniflorin (GPF), a galloylated derivative of paeoniflorin isolated from the roots of Paeonia lactiflora Pall, exerted significant inhibitory effects on proliferation and invasion of SH-SY5Y cells (an NBM cell line) and enhanced the sensitivity of SH-SY5Y cells to cisplatin in vitro. Further studies showed that GPF treatment upregulated miR-489 in NBM cells via activating AMP-activated protein kinase (AMPK). We also demonstrated that similar to GPF treatment, miR-489 exhibited a significant anti-NBM capacity. Further studies showed that miR-489 directly targeted the X-linked inhibitor of apoptosis protein (XIAP). Overall, our results indicated that GPF possessed an evident anti-NBM capacity dependent on AMPK/miR-489/XIAP pathway, providing an emerging strategy for clinical treatment of NBM.

Effect of GADD45G on the radioresistance of nasopharyngeal carcinoma cells.

The development of radioresistance by nasopharyngeal carcinoma (NPC) cells almost always results in tumor recurrence and metastasis, making clinical treatment of the disease difficult. In this study, the mechanism of radioresistance in NPC cells was investigated. First, a gene array and quantitative reverse-transcription-PCR assays were used to screen for genes exhibiting significantly altered expression in the DNA damage signaling pathway. Based on those results, GADD45G was further studied in the context of radioresistance. A GADD45G-knockout NPC cell line (CNE-2R-KO) was constructed using CRISPR-Cas9 technology and used for a comparison of differences in radioresistance with other radiosensitive and radioresistant NPC cells, as evaluated using colony formation assays. Cell cycle changes were observed using flow cytometry. Cell proliferation and migration were measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and wound healing assays, respectively. The sequencing results revealed the successful construction of the CNE-2R-KO cell line, the radiosensitivity of which was higher than that of its parent radioresistant cell line owing to the GADD45G knockout. This was likely related to the increase in the number of cells in the G1 phase and decrease in those in the S1 phase as well as the increased cell proliferation rate and decreased migratory ability. GADD45G is associated with radioresistance in NPC cells and likely has a role in the occurrence and metastasis of NPC.

YTHDC1 gene polymorphisms and neuroblastoma susceptibility in Chinese children.

Neuroblastoma (NB) is the most common extracranial tumor in children. YTHDC1, a member of RNA methylation modification binding proteins, plays critical roles in tumor occurrence and metastasis. However, it is unclear whether YTHDC1 gene polymorphisms are related to NB susceptibility. Herein, we aimed to evaluate the association between YTHDC1 gene polymorphisms (rs2293596 T>C, rs2293595 T>C, rs3813832 T>C) and susceptibility of NB by logistic regression models. In this eight-center case-control study, 898 patients with NB and 1734 healthy controls were genotyped by TaqMan assay. The results showed that rs3813832 TC genotype could significantly reduce the susceptibility of NB compared with the TT genotype [adjusted odds ratio (AOR) = 0.81, 95% confidence interval (CI) = 0.68-0.96, P = 0.018]. Combined genotype analysis revealed that individuals with 3 protective genotypes had a prominently lower NB risk than those with 0-2 protective genotypes (AOR = 0.80, 95% CI = 0.68-0.94, P = 0.006). The stratified analysis also demonstrated the protective effect of rs3813832 TC/CC and 3 protective genotypes in certain subgroups. Further functional experiments revealed that YTHDC1 siRNA-554, targeting the area near the rs3813832 T>C polymorphism site, could observably inhibit the proliferation and migration of NB cells. In conclusion, our findings highlight the involvement of YTHDC1 gene and its genetic variants in the etiology of NB.

Effect of cardiac rehabilitation training on patients with coronary heart disease: a systematic review and meta-analysis.

BACKGROUND: In recent years, the incidence of heart disease has increased and patients are younger. Cardiac rehabilitation training has been proposed to improve the prognosis of patients with heart disease. Cardiac rehabilitation includes moderate-intensity continuous training (MCT) and high-intensity interval training (HIIT). These two training methods have different effects in improving the prognosis of patients. The aim of the present study was to improve reference for patients with cardiac rehabilitation. METHODS: English databases, including PubMed, Cochrane Library, and Embase, were searched from the establishment of the database to April 2021 for randomized controlled trials (RCTs) of rehabilitation training at different intensities. RevMan 5.3 was used for the meta-analysis. RESULTS: A total of 8 articles (with a total of 465 patients) were included, including 236 patients in the experimental group and 229 patients in the control group. Different intensities of training had statistically significant differences in peak oxygen uptake [mean difference (MD): 1.21, 95% confidence interval (CI): -0.66 to 3.07, P=0.20] and the left ventricular ejection fraction difference (MD: 2.53, 95% CI: -2.10 to 7.17, P=0.28). DISCUSSION: Cardiac rehabilitation training can effectively improve the patient's cardiac function indicators and self-care ability, and reduce the incidence of cardiovascular disease (CVD). However, large-sample, multicenter, and long-term RCTs are needed to strengthen the findings of the study.

Aberrant Development of Enteric Glial Cells in the Colon of Hirschsprung's Disease.

Objective: The aim of this study was to explore the development of enteric glial cells (EGCs) in different segments of Hirschsprung's disease (HSCR). Methods: Colonic specimens from 35 children with HSCR were selected to analyze the relative expression of glial fibrillary acidic protein and S100 calcium-binding protein B using Western blotting and real-time fluorescence quantitative PCR. Immunofluorescence and immunohistochemical staining were performed to determine the distribution of myenteric EGCs and neuronal cells in different segments of HSCR. Results: There was a trend of diminished protein and mRNA expression of glial fibrillary acidic protein and S100 calcium-binding protein B from the proximal, dilated, and transitional segments to the aganglionic segment (p < 0.05). Immunofluorescence and immunohistochemistry showed that the EGCs in the aganglionic, transitional, and dilated colonic muscles were morphologically abnormal, which was consistent with the dysplasia of myenteric neurons. Conclusion: Aberrant development of myenteric EGCs was observed in the colon of HSCR, which may affect the survival of enteric neurons.

Association of a GATA Binding Protein 4 Polymorphism with the Risk of Hypospadias in the Chinese Children.

PURPOSE: GATA binding protein 4 (GATA4) has been implicated in the etiology of congenital malformation of the urogenital system. The present study investigated the influence of GATA4 polymorphisms on susceptibility to hypospadias. METHODS: We genotyped 4 potentially functional polymorphisms (rs12458, rs12825, rs884662, and rs904018) in GATA4 in the hospital-based case-control study including 410 child patients and 520 nonmalformed individuals by the TaqMan MGB method. Risk associations were assessed using unconditional logistic regression, adjusted for potential confounding factors. RESULTS: A significant association was found between rs12458 (3'-UTR of GATA4) and susceptibility to hypospadias (p = 0.008). Compared with rs12458 AA genotype individuals, those harboring the variant allele (rs12458 AT/TT) were correlated with significantly higher risk of hypospadias (AT/TT vs. AA: OR = 1.42, 95% CI = 1.17-2.35, p = 0.036). Furthermore, the rs12458T allele showed significantly decreased activity in a luciferase reporter assay, indicating a possible role of rs12458 variant in regulating the combination of microRNAs with the GATA4 mRNA. CONCLUSIONS: The present results indicate that the functional GATA4 rs12458 variant confers individuals' susceptibility to hypospadias, possibly through regulating the GATA4 expression level.

Role of GDNF, GFRα1 and GFAP in a Bifidobacterium-Intervention Induced Mouse Model of Intestinal Neuronal Dysplasia.

OBJECTIVE: To investigate the effects of glial cell-derived neurotrophic factor (GDNF), GDNF family receptor alpha 1 (GFRα1), and glial fibrillary acidic protein (GFAP) on colonic motility in a mouse model of intestinal neuronal dysplasia by intervention with Bifidobacterium and to explore the influence of Bifidobacterium on enteric glial cells (EGCs). METHODS: Western blotting and qRT-PCR were employed to detect the expression of GFRα1 and GFAP in colonic tissues of mice with or without Tlx2 mutations, and ELISA was used to detect the expression of GDNF in serum. IHC was used to detect the appearance of the ganglion cells. Subsequently, Tlx2 homozygous mutant (Tlx2-/-) mice were treated with Bifidobacterium. Colonic motility was measured before and after intervention by measuring the glass bead expelling time. The variations in abdominal circumference and GDNF, GFRα1, and GFAP expression were measured. In addition, 16SrRNA gene sequencing was performed to detect the abundance of the intestinal microbiota. RESULTS: The mRNA and protein expression of GFRα1 and GFAP was decreased in the colonic tissues of Tlx2-/- mice and GDNF expression was decreased in serum compared with Tlx2+/- and WT mice. After confirming the colonization of Bifidobacterium by 16S rRNA gene sequencing, the expelling time and abdominal distension were ameliorated, and the expression of GFAP, GDNF, and GFRα1 was increased. CONCLUSIONS: The expression of GDNF, GFRα1, and GFAP is associated with colonic motility. The altered expression of EGC-related factors suggested that Bifidobacterium may be involved in the EGC activation process. The amelioration of IND symptoms after intervention with Bifidobacterium prompted the elicitation of adjuvant therapy.

Effect of Shengmai Yin on the DNA methylation status of nasopharyngeal carcinoma cell and its radioresistant strains.

Shengmai Yin (SMY) is a Chinese herbal decoction that effectively alleviates the side effects of radiotherapy in various cancers and helps achieve radiotherapy's clinical efficacy. In this study, we explored the interaction mechanism among SMY, DNA methylation, and nasopharyngeal carcinoma (NPC). We identified differences in DNA methylation levels in NPC CNE-2 cells and its radioresistant cells (CNE-2R) using the methylated DNA immunoprecipitation array and found that CNE-2R cells showed genome-wide changes in methylation status towards a state of hypomethylation. SMY may restore its original DNA methylation status, and thus, enhance radiosensitivity. Furthermore, we confirmed that the differential gene Tenascin-C (TNC) was overexpressed in CNE-2R cells and that SMY downregulated TNC expression. This downregulation of TNC inhibited NPC cell radiation resistance, migration, and invasion. Furthermore, we found that TNC was hypomethylated in CNE-2R cells and partially restored to a hypermethylated state after SMY intervention. DNA methyltransferases 3a may be the key protein in DNA methylation of TNC.

Surgical outcomes of bladder augmentation: A comparison of three different augmentation procedures.

BACKGROUND: Augmentation cystoplasty is indispensable in many pediatric diseases, especially neurogenic bladder. Various methods and materials are used to augment the bladder, and these methods are associated with different shortcomings and complications. AIM: The present study reported the mid-term outcomes of patients undergoing various bladder augmentation procedures in a single institution, and assessed whether seromuscular cystoplasty lined with urothelium (SCLU) provided better urodynamic results than auto-augmentation (AA). METHODS: A retrospective review of 96 patients undergoing various augmentation methods between 2003 and 2018 was performed. The patients were divided into three groups according to the type of augmentation, and their outcomes were compared. All patients developed neurogenic bladder due to myelomeningocele or sacrococcygeal teratoma. The clinical data of all patients were collected. RESULTS: The mean ages at surgery in the three groups (standard cystoplasty [SC], SCLU, AA) were 10.8, 7.5, and 4.8 years, respectively, with mean follow-ups of 36, 61, and 36 mo, respectively. The mean preoperative and postoperative bladder capacities of the SC, SCLU, and AA groups were 174 ± 11.7 vs. 387 ± 13.7 (P < 0.0001), 165 ± 12.2 vs. 240 ± 14.7 (P = 0.0002), and 138 ± 16.7 vs. 181 ± 9.9 (P = 0.0360), respectively. Compared with the AA group, the SCLU procedure did not have better postoperative urodynamic parameters. Incontinence was reduced in most patients. The mean times of clean intermittent catheterization per day in the SC, SCLU, and AA groups were 5.6, 7.8, and 8.2, respectively. The main complications of the SC group were recurrent urinary tract infections (8%) and bladder calculi (6%). Re-augmentation was done in patients in the SCLU (8) and AA (3) groups. CONCLUSION: SC provided sufficient bladder capacity and improved compliance with acceptable complications. After AA and SCLU, the patients acquired limited increases in bladder capacity and compliance with a high rate of re-augmentation. Compared with AA, SCLU did not yield better postoperative urodynamic parameters.

Folate receptor-positive circulating tumor cells as a predictive biomarker for the efficacy of first-line pemetrexed-based chemotherapy in patients with non-squamous non-small cell lung cancer.

BACKGROUND: There is a lack of well-established biomarkers to predict the efficacy of pemetrexed-based chemotherapy. In this prospective phase II study, we investigated the correlation of folate receptor (FR)-positive circulating tumor cell (CTC) level with the clinical outcomes of patients with advanced non-squamous non-small cell lung cancer (nsNSCLC) when treated with pemetrexed-based chemotherapy. METHODS: A total of 98 nsNSCLC patients were enrolled. Peripheral blood was collected from each patient prior to initiation of treatment. FR-positive CTCs were enriched by immunomagnetic leukocyte depletion and quantified using ligand-targeted polymerase chain reaction (LT-PCR) method. RESULTS: Patients with relatively low CTC level (11-16 FU/3 mL, n=32) showed a significantly shorter progression-free survival (PFS) and overall survival (OS) compared with those in the "high CTC level group" (>16 FU/3mL, n=28; median PFS, 133 versus 320 days, P<0.001; median OS, 632 days versus "not reached", P=0.003). Patients in the "high CTC level group" also achieved superior objective response rate (ORR) and disease control rate (DCR) over those in the "low CTC level group" (ORR, 40.9% versus 9.5%, P=0.0339; DCR, 100% versus 81.0%, P=0.0485). The clinical outcomes of pemetrexed in the "negative-CTC group" (<11 FU/3mL, n=38) fell between the "high CTC level group" and the "low CTC level group" (median PFS, 290 days; median OS, 1,122 days; ORR: 21.2%, DCR: 93.9%). Further multivariate Cox proportional hazards regression analysis demonstrated that "high CTC level" was an independent factor that was significantly associated with better PFS [hazard ratio (HR) =0.26, 95% confidence interval (CI), 0.12-0.58, P=0.001] and OS (HR =0.23, 95% CI, 0.06-0.92, P=0.037). CONCLUSIONS: Our results implied that FR-positive CTC is a promising biomarker to predict the clinical outcome of pemetrexed-based chemotherapy in patients with advanced nsNSCLC.

Comparative Clinical Study Between Modified Ureteral Orthotopic Reimplantation and Cohen Method Under Pneumovesicum in Pediatric Patients With Hydroureteronephrosis.

Purpose: To report our initial experience with a modified ureteral orthotopic reimplantation technique under pneumovesicum and compare the outcomes vs. those obtained with the Cohen technique under pneumovesicum for the correction of primary obstructive megaureter (POM) or vesicoureteral reflux(VUR) in pediatric patients. Methods: A total of 46 patients (38 POM and 8 VUR; mean age: 16.24 months) treated with modified ureteral orthotopic reimplantation (OR) and 43 patients (34 POM and 9 VUR; mean age: 22.98 months) treated with Cohen reimplantation (CR) under pneumovesicum were included. We compared the results perioperatively and during follow-up. Results: The mean operative time was significantly shorter in the OR group (OR: 86.86 and 108.18 vs. CR: 95.14 and 124.29 min for unilateral and bilateral cases, respectively). The mean postoperative hospital stay (OR: 5.02 vs. CR: 5.07 days), blood loss (OR: 3.67 vs. CR: 3.84 ml), and follow-up time (OR: 23.17 vs. CR: 23.37 months) did not exhibit significant differences between the two groups. One patient converted to open surgery in the CR group, whereas there was no conversion in the OR group. Postoperative febrile urinary tract infection occurred in two cases in each group. Both infections were controlled using antibiotics. All patients in both groups showed improved hydroureteronephrosis, and all patients with VUR showed reflux resolution post-surgery. Conclusions: Our modified ureteral orthotopic reimplantation technique under pneumovesicum can be safely and effectively performed, achieving a high success rate that is equivalent to that obtained through the Cohen technique under pneumovesicum. Moreover, it involves a simpler procedure and shorter operation time.