Dysregulation of PD-L1 by UFMylation imparts tumor immune evasion and identified as a potential therapeutic target.

Immunotherapy of PD-L1/PD-1 blockage elicited impressive clinical benefits for cancer treatment. However, the relative low response and therapy resistance highlight the need to better understand the molecular regulation of PD-L1 in tumors. Here, we report that PD-L1 is a target of UFMylation. UFMylation of PD-L1 destabilizes PD-L1 by synergizing its ubiquitination. Inhibition of PD-L1 UFMylation via silencing of UFL1 or Ubiquitin-fold modifier 1 (UFM1), or the defective UFMylation of PD-L1, stabilizes the PD-L1 in multiple human and murine cancer cells, and undermines antitumor immunity in vitro and mice, respectively. Clinically, UFL1 expression was decreased in multiple cancers and lower expression of UFL1 negatively correlated with the response of anti-PD1 therapy in melanoma patients. Moreover, we identified a covalent inhibitor of UFSP2 that promoted the UFMylation activity and contributed to the combination therapy with PD-1 blockade. Our findings identified a previously unrecognized regulator of PD-L1 and highlighted UFMylation as a potential therapeutic target.

The Effect of Ethephon on Ethylene and Chlorophyll in Zoysia japonica Leaves.

Zoysia japonica (Zoysia japonica Steud.) is a kind of warm-season turfgrass with many excellent characteristics. However, the shorter green period and longer dormancy caused by cold stress in late autumn and winter are the most limiting factors affecting its application. A previous transcriptome analysis revealed that ethephon regulated genes in chlorophyll metabolism in Zoysia japonica under cold stress. Further experimental data are necessary to understand the effect and underlying mechanism of ethephon in regulating the cold tolerance of Zoysia japonica. The aim of this study was to evaluate the effects of ethephon by measuring the enzyme activity, intermediates content, and gene expression related to ethylene biosynthesis, signaling, and chlorophyll metabolism. In addition, the ethylene production rate, chlorophyll content, and chlorophyll a/b ratio were analyzed. The results showed that ethephon application in a proper concentration inhibited endogenous ethylene biosynthesis, but eventually promoted the ethylene production rate due to its ethylene-releasing nature. Ethephon could promote chlorophyll content and improve plant growth in Zoysia japonica under cold-stressed conditions. In conclusion, ethephon plays a positive role in releasing ethylene and maintaining the chlorophyll content in Zoysia japonica both under non-stressed and cold-stressed conditions.

Development of a nomogram to predict negative postoperative behavioral changes based on a prospective cohort.

BACKGROUND: It is believed that negative postoperative behavioral changes (NPOBC) is associated with negative perioperative outcomes in children. The importance of development of a predictive model of NPOBC was noted. This study aims to identify potential risk factors develop a nomogram to predict NPOBC on postoperative day 3 based on a prospective cohort. METHODS: A prospective observational study was conducted on children(American Society of Anesthesiologists I ~ III) aged 2 ~ 12 years who underwent selective surgery under general anesthesia between September 2022 and February 2023. The patient's clinical data were analyzed. The method of measuring NPOBC is with the The Posthospital Behaviour Questionnaire (PHBQ), and all of children remained hospitalized at the time of assessment. The enrolled patients were categorized into the NPOBC group and the non-NPOBC group according to if children developed NPOBC on postoperative day 3. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors and develop the nomogram to predict NPOBC. Internal validation was performed using the parametric bootstrapping method. RESULTS: One hundred ninety-two patients were enrolled in the study, 44.8% (86/192 patients) of children developed NPOBC on postoperative day 3. Univariate and multivariate logistic regression analysis demonstrated that the Pediatric Anesthesia Behavior (PAB) score (OR: 1.23, 95%CI: 1.14-1.33), cerebral desaturation (OR: 1.16, 95%CI: 1.02-1.32), and postoperative pain score (OR: 1.07, 95%CI: 1.02-1.13) were independent predictors for NPOBC on postoperative day 3 (P < 0.05). They were used to develop the prediction model. The calibration curve demonstrated satisfied discrimination and calibration of the prediction model. The model presented with good discriminative ability (area under the receiver operating characteristic curve: 0.762 [95%CI: 0.691-0.833]). The decision curve analysis also revealed the great clinical utility of the nomogram. CONCLUSION: Based on our prospective observational study, pre-anesthesia patients with higher PAB scores, presence of cerebral desaturation, and higher postoperative pain score were more likely to develop NPOBC on postoperative day 3. We established and validated a nomogram for predicting NPOBC, which could help assess patients individually, identify high-risk groups of NPOBC and improve patient prognosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-2,200,059,776. Registered 11 May 2022.

Molecular Mechanism Pathways of Natural Compounds for the Treatment of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and its incidence continues to increase each year. Yet, there is still no definitive drug that can stop its development. This review focuses mainly on lipotoxicity, oxidative stress, inflammation, and intestinal flora dysbiosis to understand NAFLD's pathogenesis. In this review, we used NCBI's PubMed database for retrieval, integrating in vivo and in vitro experiments to reveal the therapeutic effects of natural compounds on NAFLD. We also reviewed the mechanisms by which the results of these experiments suggest that these compounds can protect the liver from damage by modulating inflammation, reducing oxidative stress, decreasing insulin resistance and lipid accumulation in the liver, and interacting with the intestinal microflora. The natural compounds discussed in these papers target a variety of pathways, such as the AMPK pathway and the TGF-ß pathway, and have significant therapeutic effects. This review aims to provide new possible therapeutic lead compounds and references for the development of novel medications and the clinical treatment of NAFLD. It offers fresh perspectives on the development of natural compounds in preventing and treating NAFLD.

Effect of radiofrequency therapy on HPV16-E7 lentivirus infection in the reproductive tract of mice and its effect on immune function of splenic lymphocytes.

OBJECTIVE: To investigate the effect of radiofrequency therapy (RFT) on HPV16-E7 lentivirus infection in the reproductive tract of mice and reveal its effect on immune function of splenic lymphocytes. MATERIALS AND METHODS: The mouse reproductive tract model was established by infection with HPV16-E7 lentivirus. Fluorescence microscope was used to evaluate successful injection. The expression of HPV16-E7 protein was detected by Western blotting test. The levels of CD4+ and CD8+ were determined by flow cytometry, and the ratio was calculated. The proliferation of splenic lymphocytes was detected by MTT assay. Expression of Interleukin (IL)-2 and interferon-γ (IFN-γ) messenger RNA (mRNA) in lymphocyte was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Fluorescence microscope determined the successful injection of HPV16-E7 lentivirus. Compared with model group, RFT treatment decreased HPV16-E7 protein, and increased CD4+/CD8+ ratio and the proliferation activity of splenic lymphocytes. Besides, RFT treatment increased the mRNA expression levels of IL-2 and IFN-γ compared to the model group. In particular, the proliferation activity of spleen lymphocytes and the expression levels of IL-2 mRNA and IFN-γ mRNA in RFT were higher at 12 days than at 6 days after treatment. CONCLUSION: RFT could eliminate HPV16-E7 lentivirus infection in the reproductive tract of mice, and the mechanism was related to the immune system.

Molecular Mechanistic Pathways Targeted by Natural Compounds in the Prevention and Treatment of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is one of the most common complications of diabetes, and its prevalence is still growing rapidly. However, the efficient therapies for this kidney disease are still limited. The pathogenesis of DKD involves glucotoxicity, lipotoxicity, inflammation, oxidative stress, and renal fibrosis. Glucotoxicity and lipotoxicity can cause oxidative stress, which can lead to inflammation and aggravate renal fibrosis. In this review, we have focused on in vitro and in vivo experiments to investigate the mechanistic pathways by which natural compounds exert their effects against the progression of DKD. The accumulated and collected data revealed that some natural compounds could regulate inflammation, oxidative stress, renal fibrosis, and activate autophagy, thereby protecting the kidney. The main pathways targeted by these reviewed compounds include the Nrf2 signaling pathway, NF-κB signaling pathway, TGF-ß signaling pathway, NLRP3 inflammasome, autophagy, glycolipid metabolism and ER stress. This review presented an updated overview of the potential benefits of these natural compounds for the prevention and treatment of DKD progression, aimed to provide new potential therapeutic lead compounds and references for the innovative drug development and clinical treatment of DKD.

Effect of hemoglobin content on cerebral oxygen saturation during surgery for scoliosis in pediatric patients.

BACKGROUND: Although regional cerebral oxygen saturation (rScO2) monitoring has been widely used in clinical practice, the relationship between hemoglobin (dHB) content and rScO2 is incompletely understood. The aim of this study was to analyze the effect of hemoglobin content on rScO2 in pediatric patients undergoing general anesthesia for correction of scoliosis. METHODS: Ninety-two pediatric patients aged 3 to 14 years undergoing scoliosis correction surgery were enrolled. Continuous monitoring of bilateral regional cerebral oxygen saturation by near-infrared spectroscopy (NIRS, CASMED, USA) was performed after entering the operation room. rScO2 was recorded when the patients entered the operating room (T0, baseline), after anesthesia induced intubation (T1), and after radial artery puncture (T2). The lowest value of rScO2 during surgery was also recorded. The arterial blood pressure (ABP), heart rate (HR), pulse oxygen saturation (SpO2), end tidal carbon dioxide partial pressure (PetCO2) were continuously recorded. Patients were classified as low rScO2 or high rScO2 group according to whether the lowest intraoperative rScO2 was 15% lower than the baseline value. An analysis and comparison of differences in hemoglobin content in these two groups was carried out. RESULTS: The preoperative hemoglobin-postoperative hemoglobin of patients in the high rScO2 group was significantly lower than that in the low rScO2 group (t = - 7.86, p < 0.01), the amount of bleeding during the operation was also less than that in the low rScO2 group (t = - 6.05, p < 0.01), and the systolic pressure of patients was higher than that in the low rScO2 group (t = 4.27, p < 0.01). CONCLUSIONS: The decrease in hemoglobin level which occurs during surgery leads to a decrease in cerebral oxygen saturation. In order to ensure patient safety during surgery, it is necessary to carry out volume management and appropriate transfusion and fluid replacement in a timely manner. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800016359 . Registered 28 May 2018.

Shh-Yap signaling controls hepatic ductular reactions in CCl4 -induced liver injury.

Carbon tetrachloride (CCl4 ) exposure can induce hepatic ductular reactions. To date, however, the related mechanism remains largely unknown. Sonic hedgehog (Shh) and Yes-associated protein (Yap) signaling are correlated with liver injury and regeneration. Herein, we investigated the role of Shh and Yap signaling in the fate of ductular reaction cells in CCl4 -treated livers and the possible mechanisms. Wild-type and Shh-EGFP-Cre male mice were exposed to CCl4 (2 mL/kg), and then treated with or without the Shh signaling inhibitor Gant61. The level of liver injury, proliferation of ductular reaction cells, and expression levels of mRNA and protein related to the Shh and Yap signaling components were assessed. Results showed that CCl4 treatment induced liver injury and promoted activation and proliferation of ductular reaction cells. In addition, CCl4 induced the expression of Shh ligands in hepatocytes, accompanied by activation of Shh and Yap1 signaling in the liver. Furthermore, administration of Gant61 ameliorated liver regeneration, inhibited hepatic ductular reactions, and decreased Shh and Yap1 signaling activity. Thus, Shh-Yap1 signaling appears to play an integral role in the proliferation of ductular reaction cells in CCl4 -induced liver injury. This study should improve our understanding of the mechanism of CCl4 -induced liver injury and ductular reactions and provide support for future investigations on liver disease therapy.

Bionic Birdlike Imaging Using a Multi-Hyperuniform LED Array.

Digital cameras obtain color information of the scene using a chromatic filter, usually a Bayer filter, overlaid on a pixelated detector. However, the periodic arrangement of both the filter array and the detector array introduces frequency aliasing in sampling and color misregistration during demosaicking process which causes degradation of image quality. Inspired by the biological structure of the avian retinas, we developed a chromatic LED array which has a geometric arrangement of multi-hyperuniformity, which exhibits an irregularity on small-length scales but a quasi-uniformity on large scales, to suppress frequency aliasing and color misregistration in full color image retrieval. Experiments were performed with a single-pixel imaging system using the multi-hyperuniform chromatic LED array to provide structured illumination, and 208 fps frame rate was achieved at 32 × 32 pixel resolution. By comparing the experimental results with the images captured with a conventional digital camera, it has been demonstrated that the proposed imaging system forms images with less chromatic moiré patterns and color misregistration artifacts. The concept proposed verified here could provide insights for the design and the manufacturing of future bionic imaging sensors.

Natural Xanthine Oxidase Inhibitor 5-O-Caffeoylshikimic Acid Ameliorates Kidney Injury Caused by Hyperuricemia in Mice.

Xanthine oxidase (XOD) inhibition has long been considered an effective anti-hyperuricemia strategy. To identify effective natural XOD inhibitors with little side effects, we performed a XOD inhibitory assay-coupled isolation of compounds from Smilacis Glabrae Rhizoma (SGR), a traditional Chinese medicine frequently prescribed as anti-hyperuricemia agent for centuries. Through the in vitro XOD inhibitory assay, we obtained a novel XOD inhibitor, 5-O-caffeoylshikimic acid (#1, 5OCSA) with IC50 of 13.96 µM, as well as two known XOD inhibitors, quercetin (#3) and astilbin (#6). Meanwhile, we performed in silico molecular docking and found 5OCSA could interact with the active sites of XOD (PDB ID: 3NVY) with a binding energy of -8.6 kcal/mol, suggesting 5OCSA inhibits XOD by binding with its active site. To evaluate the in vivo effects on XOD, we generated a hyperuricemia mice model by intraperitoneal injection of potassium oxonate (300 mg/kg) and oral gavage of hypoxanthine (500 mg/kg) for 7 days. 5OCSA could inhibit both hepatic and serum XOD in vivo, together with an improvement of histological and multiple serological parameters in kidney injury and HUA. Collectively, our results suggested that 5OCSA may be developed into a safe and effective XOD inhibitor based on in vitro, in silico and in vivo evidence.

miR-188-5p inhibits apoptosis of neuronal cells during oxygen-glucose deprivation (OGD)-induced stroke by suppressing PTEN.

The miRNAs and mRNAs are found to play a crucial role in modulating different diseases including stroke, according to the recent evidence. The current study is aimed at assessing the functional role played by miR-188-5p in the regulation of cell apoptosis and viability in OGD-induced human neural cell line HNC. With the help of RT-qPCR, the authors determined miR-188-5p as well as its putative target PTEN among OGD-treated cells in different treatment times. The cell viability was assessed through CCK-8 assay while the cell transfection either upregulated or may have silenced the genes. Both Western Blot as well as RT-qPCR found the proliferation biomarkers such as Ki87 and PCNA in addition to apoptosis biomarkers such as caspase-8 and caspase-3. The luciferase activity was tracked by conducting luciferase assay. The researchers observed an elevation in the expression of miR-188-5p while the PTEN got downregulated in Human Neural Cell line HNC with increase in the time span. The expressions of miR-188-5p and PTEN got increased with increasing OGD treatment time while the Luciferase reassured the binding site. The cell viability was suppressed by the overexpression of miR-188-5p which further inhibited the apoptosis biomarkers too. Meanwhile, it was understood that the results could be reversed to some extent with the inhibition of PTEN. The study findings from in vitro investigations yielded promising results and provided excellent insights about the fundamental molecular mechanisms of miR-188-5p involved in stroke via PTEN. This could be considered as a potential therapeutic axis among stroke patients in the near future.

Association of tidal volume during mechanical ventilation with postoperative pulmonary complications in pediatric patients undergoing major scoliosis surgery.

BACKGROUND: The use of lung-protective ventilation strategies with low tidal volumes may reduce the occurrence of postoperative pulmonary complications. However, evidence of the association of intraoperative tidal volume settings with pulmonary complications in pediatric patients undergoing major spinal surgery is insufficient. AIMS: This study examined whether postoperative pulmonary complications were related to tidal volume in this population and, if so, what factors affected the association. METHODS: In this retrospective cohort study, data from pediatric patients (<18 years old) who underwent posterior spinal fusion between 2016 and 2018 were collected from the hospital electronic medical record. The associations between tidal volume and the clinical outcomes were examined by multivariate logistic regression and stratified analysis. RESULTS: Postoperative pulmonary complications occurred in 41 (16.1%) of 254 patients who met the inclusion criteria. For the entire cohort, tidal volume was associated with an elevated risk of pulmonary complications (adjusted odds ratio [OR] per 1 mL/kg ideal body weight [IBW] increase in tidal volume, 1.28; 95% confidence interval [CI], 1.01-1.63, P = .038). In subgroup analysis, tidal volume was associated with an increased risk of pulmonary complications in patients older than 3 years (adjusted OR per 1 mL/kg IBW increase in tidal volume, 1.43, 95% CI: 1.12-1.84), but not in patients aged 3 years or younger (adjusted OR, 0.78, 95% CI: 0.46-1.35), indicating a significant age interaction (P = .035). CONCLUSION: In pediatric patients undergoing major spinal surgery, high tidal volume was associated with an elevated risk of postoperative pulmonary complications. However, the effect of tidal volume on pulmonary outcomes in the young subgroup (≤3 years) differed from that in the old (>3 years). Such information may help to optimize ventilation strategy for children of different ages.

[Association of non-thyroidal illness syndrome with interleukin-6 and interleukin-10 in critically ill children with sepsis].

OBJECTIVE: To study the incidence rate of non-thyroidal illness syndrome (NTIS) in critically ill children with or without sepsis and the association of NTIS with interleukin-6 (IL-6) and interleukin-10 (IL-10). METHODS: A retrospective analysis was performed on the medical data of 97 children with sepsis (sepsis group) and 80 non-sepsis children with bacterial infection (non-sepsis group). The correlations of IL-6 and IL-10 with the thyroid function parameters triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) were analyzed. RESULTS: There were no significant differences in age and sex between the sepsis and non-sepsis groups (P>0.05). Compared with the non-sepsis group, the sepsis group had a significantly higher Sequential Organ Failure Assessment score, a significantly longer length of hospital stay, and a significantly higher rate of use of ventilator (P<0.05). As for inflammation markers, the sepsis group had significantly higher levels of C-reactive protein, procalcitonin, and IL-6 than the non-sepsis group (P<0.05). As for thyroid function parameters, the sepsis group had significantly lower levels of T3, T4, free T3, free T4, and TSH than the non-sepsis group (P<0.05). Compared with the non-sepsis group, the sepsis group had significantly higher incidence rates of NTIS, low T3 and T4, and low TSH (P<0.001). The correlation analysis revealed that IL-6 level was not correlated with T3, T4, and TSH levels in children with or without sepsis (P>0.05), but the pooled analysis of the two groups showed that IL-6 level was negatively correlated with T3 and T4 levels (P<0.001). CONCLUSIONS: Children with sepsis have a higher incidence rate of NTIS than those without sepsis. The high level of IL-6 may be associated with the development of NTIS.

Suppression of the quantization error in a fiber optic gyroscope using a double-electrode-pair multifunction integrated-optic circuit.

The measuring accuracy of the fiber optic gyroscope (FOG) for weak signals under very short sampling time is significantly impacted by the quantization error, impeding its application in high-speed measurement and real-time control. In this work, we propose and implement a double-electrode-pair multifunction integrated-optic circuit (MIOC), which contains an additional pair of short electrodes besides the conventional electrode-pair. Taking advantage of the better modulating precision of the additional electrode-pair, the digital feedback is more refined and the quantization error in the FOG output is significantly suppressed. The driving circuits and the control scheme of the proposed MIOC are specially designed for FOGs. Experimental results show that the resolution for extremely small angular rates at short smoothing times is significantly improved. This work provides the potential of the applications in high-speed measuring and controlling systems for high-precision FOGs.

Imaging using hyperuniform sampling with a single-pixel camera.

Digital cameras use detector arrays with regular geometry for optical sampling. Though regular arrangement was demonstrated to be optimal for two-dimensional sampling, it causes aliasing at high frequencies exceeding its Nyquist limit. Here, we proposed a randomization procedure to generate 2D hyperuniform patterns that can be used to suppress aliasing in image retrieval. Experiments are performed using a single-pixel camera, where the sampling patterns do not necessarily follow a fixed Cartesian geometry. Results demonstrate that the images reconstructed by hyperuniform patterns have a lower root mean squared error and exhibit less moiré fringes at high frequencies than the images reconstructed by regular square patterns do. Furthermore, the same conclusion can be applied to the production of conventional detector arrays, where manufacturing imperfection could be utilized to suppress frequency aliasing in image retrieval.

Loop gain stabilizing with an all-digital automatic-gain-control method for high-precision fiber-optic gyroscope.

For a fiber-optic gyroscope (FOG) using electronic dithers to suppress the dead zone, without a fixed loop gain, the deterministic compensation for the dither signals in the control loop of the FOG cannot remain accurate, resulting in the dither residuals in the FOG rotation rate output and the navigation errors in the inertial navigation system. An all-digital automatic-gain-control method for stabilizing the loop gain of the FOG is proposed. By using a perturbation square wave to measure the loop gain of the FOG and adding an automatic gain control loop in the conventional control loop of the FOG, we successfully obtain the actual loop gain and make the loop gain converge to the reference value. The experimental results show that in the case of 20% variation in the loop gain, the dither residuals are successfully eliminated and the standard deviation of the FOG sampling outputs is decreased from 2.00 deg/h to 0.62 deg/h (sampling period 2.5 ms, 10 points smoothing). With this method, the loop gain of the FOG can be stabilized over the operation temperature range and in the long-time application, which provides a solid foundation for the engineering applications of the high-precision FOG.

Genomic editing of the HIV-1 coreceptor CCR5 in adult hematopoietic stem and progenitor cells using zinc finger nucleases.

The HIV-1 coreceptor CCR5 is a validated target for HIV/AIDS therapy. The apparent elimination of HIV-1 in a patient treated with an allogeneic stem cell transplant homozygous for a naturally occurring CCR5 deletion mutation (CCR5(Δ32/Δ32)) supports the concept that a single dose of HIV-resistant hematopoietic stem cells can provide disease protection. Given the low frequency of naturally occurring CCR5(Δ32/Δ32) donors, we reasoned that engineered autologous CD34(+) hematopoietic stem/progenitor cells (HSPCs) could be used for AIDS therapy. We evaluated disruption of CCR5 gene expression in HSPCs isolated from granulocyte colony-stimulating factor (CSF)-mobilized adult blood using a recombinant adenoviral vector encoding a CCR5-specific pair of zinc finger nucleases (CCR5-ZFN). Our results demonstrate that CCR5-ZFN RNA and protein expression from the adenoviral vector is enhanced by pretreatment of HSPC with protein kinase C (PKC) activators resulting in >25% CCR5 gene disruption and that activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway is responsible for this activity. Importantly, using an optimized dose of PKC activator and adenoviral vector we could generate CCR5-modified HSPCs which engraft in a humanized mouse model (albeit at a reduced level) and support multilineage differentiation in vitro and in vivo. Together, these data establish the basis for improved approaches exploiting adenoviral vector delivery in the modification of HSPCs.

Influences of laser source on phase-sensitivity optical time-domain reflectometer-based distributed intrusion sensor.

This paper investigates the influences of laser source on distributed intrusion sensor based on a phase-sensitivity optical time-domain reflectometer (φ-OTDR). A numerical simulation is performed to illustrate the relationships between trace-to-trace fluctuations and frequency drift rate as well as pulse width, and fluctuations ratio coefficient (FRC) is proposed to evaluate the level of trace-to-trace fluctuations. The simulation results show that the FRC grows with increasing frequency drift rate and pulse width, reaches, and maintains the peak value when the frequency drift rate and/or the pulse width are high enough. Furthermore, experiments are implemented using a φ-OTDR prototype with a low frequency drift laser (<5 MHz/min), of which the high frequency drift rate is simulated by frequency sweeping. The good agreement of experimental with simulated results in the region of high frequency drift rate validates the theoretical analysis, and the huge differences between them in the region of low frequency drift rate indicate the place of laser frequency drift among system noises. The conclusion is useful for choosing laser sources and improving the performance of φ-OTDR.

Urethrocutaneous fistula and glans dehiscence formation of hypospadias surgery in patients receiving caudal block vs. non-caudal block: A meta-analysis.

BACKGROUND: This meta-analysis aimed to evaluate the difference in postoperative complications as urethrocutaneous fistula or glans dehiscence, in children undergoing primary hypospadias repair with caudal block (CB) versus non-caudal block (NCB). METHODS: Data were obtained from MEDLINE, Embase, Web of Science, and the Cochrane Library. Comparative studies of CB versus NCB were identified, with reports of complications published or presented until October 2022. Subgroup analyses were performed based on study type, meatal location (distal only), type of NCB, surgeon and technique, and concentration and dose of anesthetics. RESULTS: Compared to the reference group of NCB, CB was not significantly associated with the development of complications following primary hypospadias repair (OR 1.40, 95 % CI 0.88-2.23). After adjusting for confounding factors, such as type of study(OR 1.51, 95%CI: 0.29-7.91), type of NCB[PB (OR 1.82, 95 % CI: 0.87-3.84), GA (OR 1.26, 95 % CI: 0.39-4.04)], meatal location (distal only) (OR 1.22, 95 % CI: 0.61-2.43), surgeon and technique (OR 1.37, 95 % CI: 0.59-3.14) and concentration and dose of anesthetics(OR 2.74, 95 % CI: 0.82-9.20), subgroup analyses revealed no significant association between CB and NCB (P > 0.05). DISCUSSION: Previous studies have found a correlation between CB and increased incidence of postoperative complications (urethrocutaneous fistula or glans dehiscence) of hypospadias, but different literature have suggested that surgical technique, surgical duration and the severity of hypospadias, rather than CB, are closely related to the occurrence of complications. In order to reduce confounding factors, subgroup analyses were conducted. The results showed that no correlation could be found in postoperative complications and CB. CONCLUSIONS: This meta-analysis compared the incidence of urethrocutaneous fistula or glans dehiscence in the CB and NCB groups for primary hypospadias repair in children, indicating that no clear correlation could be found in postoperative complications and CB. Subgroup analyses on study type, type of NCB, meatal location (distal only), surgeon and technique, and regional anesthetic concentration and dose supported this conclusion.

Radical-Mediated Decarboxylative C-C and C-S Couplings of Carboxylic Acids via Iron Photocatalysis.

Despite the significant success of decarboxylative radical reactions, the catalytic systems vary considerably upon different radical acceptors, requiring renewed case-by-case reaction optimization. Herein, we developed an iron catalytic condition that enables the highly efficient decarboxylation of various carboxylic acids for a range of radical transformations. This operationally simple protocol was amenable to a wide array of radical acceptors, delivering structurally diverse oxime ethers, alkenylation, alkynylation, thiolation, and amidation products in useful to excellent yields (>40 examples, up to 95% yield).