Wolbachia mediates crosstalk between miRNA and Toll pathways to enhance resistance to dengue virus in Aedes aegypti.

The obligate endosymbiont Wolbachia induces pathogen interference in the primary disease vector Aedes aegypti, facilitating the utilization of Wolbachia-based mosquito control for arbovirus prevention, particularly against dengue virus (DENV). However, the mechanisms underlying Wolbachia-mediated virus blockade have not been fully elucidated. Here, we report that Wolbachia activates the host cytoplasmic miRNA biogenesis pathway to suppress DENV infection. Through the suppression of the long noncoding RNA aae-lnc-2268 by Wolbachia wAlbB, aae-miR-34-3p, a miRNA upregulated by the Wolbachia strains wAlbB and wMelPop, promoted the expression of the antiviral effector defensin and cecropin genes through the Toll pathway regulator MyD88. Notably, anti-DENV resistance induced by Wolbachia can be further enhanced, with the potential to achieve complete virus blockade by increasing the expression of aae-miR-34-3p in Ae. aegypti. Furthermore, the downregulation of aae-miR-34-3p compromised Wolbachia-mediated virus blockade. These findings reveal a novel mechanism by which Wolbachia establishes crosstalk between the cytoplasmic miRNA pathway and the Toll pathway via aae-miR-34-3p to strengthen antiviral immune responses against DENV. Our results will aid in the advancement of Wolbachia for arbovirus control by enhancing its virus-blocking efficiency.

High-Contrast Photoacoustic Imaging of Localized Cysteine in Orthotopic Breast Cancer Enabled by A Totally-Caged Methylene Blue Probe.

High-contrast photoacoustic sensing imaging (PASI) was greatly determined by optical absorption changes of the absorbers usually enabled by activatable probes via controllably converting the absorbed electromagnetic energy to ultrasound waves. However, most of current photoacoustic probes still suffer from limited imaging contrast towards specific species because of their small absorption spectral changes in the near infrared (NIR) region. Herein, we developed a methylene blue-based photoacoustic probe with its NIR optical absorption totally caged, which could afford dramatical "OFF-to-ON" absorption transition for high-contrast photoacoustic imaging towards the localized cysteine. The rationally designed methylene blue-based probe for cysteine (MB-Cys) would keep in off state with almost no absorption in NIR region, while upon activated by cysteine through cyclization reaction with acrylates, it would reconstruct the π-conjugation system to release the free methylene blue with strong absorption centered at 665 nm (>130-fold enhancement). The unique responsive behavior could enable the PASI for photoacoustic mapping the cysteine in orthotopic breast cancer in a high-contrast manner. Therefore, this work established an up-to-date strategy to originally eliminate the background photoacoustic signal for PASI to accurately monitor cysteine in vivo.

Peptide Drug Design Using Alchemical Free Energy Calculation: An Application and Validation on Agonists of Ghrelin Receptor.

With recent large-scale applications and validations, the relative binding free energy (RBFE) calculated using alchemical free energy methods has been proven to be an accurate measure to probe the binding of small-molecule drug candidates. On the other hand, given the flexibility of peptides, it is of great interest to find out whether sufficient sampling could be achieved within the typical time scale of such calculation, and a similar level of accuracy could be reached for peptide drugs. However, the systematic evaluation of such calculations on protein-peptide systems has been less reported. Most reported studies of peptides were restricted to a limited number of data points or lacking experimental support. To demonstrate the applicability of the alchemical free energy method for protein-peptide systems in a typical real-world drug discovery project, we report an application of the thermodynamic integration (TI) method to the RBFE calculation of ghrelin receptor and its peptide agonists. Along with the calculation, the synthesis and in vitro EC50 activity of relamorelin and 17 new peptide derivatives were also reported. A cost-effective criterion to determine the data collection time was proposed for peptides in the TI simulation. The average of three TI repeats yielded a mean absolute error of 0.98 kcal/mol and Pearson's correlation coefficient (R) of 0.77 against the experimental free energy derived from the in vitro EC50 activity, showing good repeatability of the proposed method and a slightly better agreement than the results obtained from the arbitrary time frames up to 20 ns. Although it is limited by having one target and a deduced binding pose, we hope that this study can add some insights into alchemical free energy calculation of protein-peptide systems, providing theoretical assistance to the development of peptide drugs.

Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome in initiating ART among HIV-Infected patients in China-risk factors and management.

BACKGROUND: China is a country burdened with a high incidence of both tuberculosis (TB) and HIV, Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication in TB and HIV co-infected patients, but data from China are limited. Additionally, as an integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) regimen becomes the first-line treatment, concerns have arisen regarding the potential increase in the incidence of paradoxical TB-IRIS. Nevertheless, the existing data are inconclusive and contradictory. METHODS: We conducted a retrospective study at Chongqing Public Health Clinical Center from January 2018 to December 2021. We collected demographic and clinical data of HIV/TB co-infected patients who initiated ART. We described the patient characteristics, identified predictors for TB-IRIS, and determined clinical outcomes. The Statistical Package for Social Science (SPSS 25) was used to analyse the data. Continuous variables were compared using Student's t-test or rank sum test. Counting data were compared using the chi-square test or Fisher's exact test. The variables with statistical significance in the univariate analysis were added to the binary logistic regression. A p-value less than 0.05 was considered statistically significant. RESULTS: A total of 384 patients co-infected with naive HIV and pulmonary TB (PTB) who were given ATT and ART combination were included. 72 patients (18.8%) developed paradoxical TB-IRIS with a median of 15 (12, 21) days after initiating ART. Baseline age ≤ 40years, CD4 + T-cell counts ≤ 50cells/µL, HIV viral load ≥ 500,000 copies/mL were found to be significantly associated with development of paradoxical TB-IRIS. Mortality rates were similar in the TB-IRIS (n = 5, 6.9%) group and non-TB-IRIS (n = 13, 4.2%) group. Interestingly, CD4+ T-cell counts recovery post-ART was significant higher in the TB-IRIS group when compared to the non-TB-IRIS group at the end of 24 weeks (P = 0.004), as well as at 48 weeks (P = 0.015). In addition, we consider that INSTI- based ART regimen do not increased the risk of Paradoxical TB-IRIS. CONCLUSION: Paradoxical TB-IRIS, while often leading to clinical deterioration and hospitalization, is generally manageable. It appears to have a positive impact on the recovery of CD4 + T-cell counts over time. Importantly, our data suggest that INSTI-based ART regimens do not elevate the risk of TB-IRIS. Thus, paradoxical TB-IRIS should not be considered an impediment to initiating ART in adults with advanced immunodeficiency, except in the case of tuberculous meningitis (TBM).

Dual chemodynamic/photothermal therapeutic nanoplatform based on DNA-functionalized prussian blue.

The combination of chemodynamic therapy and photothermal therapy has a promising application owing to its impressive anti-cancer effects. However, the degradability of the material and the lack of targeting severely limit its further clinical application. Herein, DNAs containing nucleolin aptamer (AS1411) and different bases sequences were used to functionalize PB NPs for the targeted treatment. Compared to prussian blue, DNA-functionalized prussian blue does not reduce the photothermal properties of prussian blue. Moreover, DNA confers DNA-functionalized prussian blue targeting and higher enzymatic activity, thereby achieving a more effective combination of chemodynamic and photothermal treatment. The therapeutic efficacy of this nanoplatform was evaluated in vivo and in vitro experiments, exhibiting that DNA-functionalized prussian blue nanozyme can maximize the precise control of the therapeutic effect, reduce the toxic and side effects caused by non-specific accumulation on other normal cells, and effectively achieve targeted killing of cancer cells. This work demonstrates that DNA-functionalized prussian blue can improve the efficiency of combined tumor treatment and enhance the application value of prussian blue in tumor treatment, which is expected to provide theoretical support for clinical application.

De novo design of a nanoregulator for the dynamic restoration of ovarian tissue in cryopreservation and transplantation.

The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain.

Advancements in Photothermal Therapy Using Near-Infrared Light for Bone Tumors.

Bone tumors, particularly osteosarcoma, are prevalent among children and adolescents. This ailment has emerged as the second most frequent cause of cancer-related mortality in adolescents. Conventional treatment methods comprise extensive surgical resection, radiotherapy, and chemotherapy. Consequently, the management of bone tumors and bone regeneration poses significant clinical challenges. Photothermal tumor therapy has attracted considerable attention owing to its minimal invasiveness and high selectivity. However, key challenges have limited its widespread clinical use. Enhancing the tumor specificity of photosensitizers through targeting or localized activation holds potential for better outcomes with fewer adverse effects. Combinations with chemotherapies or immunotherapies also present avenues for improvement. In this review, we provide an overview of the most recent strategies aimed at overcoming the limitations of photothermal therapy (PTT), along with current research directions in the context of bone tumors, including (1) target strategies, (2) photothermal therapy combined with multiple therapies (immunotherapies, chemotherapies, and chemodynamic therapies, magnetic, and photodynamic therapies), and (3) bifunctional scaffolds for photothermal therapy and bone regeneration. We delve into the pros and cons of these combination methods and explore current research focal points. Lastly, we address the challenges and prospects of photothermal combination therapy.

[In vitro expression and functional analyses of the mutants p.R243Q, p.R241C and p.Y356X of the human phenylalanine hydroxylase]. / äººè‹¯ä¸™æ°¨é ¸ç¾ŸåŒ–é ¶çªå˜ä½“p.R243Q、p.R241C和p.Y356Xçš„ä½“å¤–è¡¨è¾¾åŠåŠŸèƒ½ç ”ç©¶.

OBJECTIVES: To study the in vitro expression of three phenylalanine hydroxylase (PAH) mutants (p.R243Q, p.R241C, and p.Y356X) and determine their pathogenicity. METHODS: Bioinformatics techniques were used to predict the impact of PAH mutants on the structure and function of PAH protein. Corresponding mutant plasmids of PAH were constructed and expressed in HEK293T cells. Quantitative reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the three PAH mutants, and their protein levels were assessed using Western blot and enzyme-linked immunosorbent assay. RESULTS: Bioinformatics analysis predicted that all three mutants were pathogenic. The mRNA expression levels of the p.R243Q and p.R241C mutants in HEK293T cells were similar to the mRNA expression level of the wild-type control (P>0.05), while the mRNA expression level of the p.Y356X mutant significantly decreased (P<0.05). The PAH protein expression levels of all three mutants were significantly reduced compared to the wild-type control (P<0.05). The extracellular concentration of PAH protein was reduced in the p.R241C and p.Y356X mutants compared to the wild-type control (P<0.05), while there was no significant difference between the p.R243Q mutant and the wild type control (P>0.05). CONCLUSIONS: p.R243Q, p.R241C and p.Y356X mutants lead to reduced expression levels of PAH protein in eukaryotic cells, with p.R241C and p.Y356X mutants also affecting the function of PAH protein. These three PAH mutants are to be pathogenic.

Progress in programmed cell death-1/programmed cell death-ligand 1 pathway inhibitors and binding mode analysis.

Programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) plays an important role in negative regulating immunity. The search for effective PD-1/PD-L1 inhibitors has been at the cutting-edge of academic and industrial medicinal chemistry, leading to the emergence of 16 clinical candidate drugs and the launch of six monoclonal antibodies (mAbs) drugs. However, due to the unclear mechanism of the interaction between drugs and substances in vivo, the screening of preclinical drugs often takes a long time. In order to shorten the time of drug development as much as possible, the binding mode analysis that can simulate the interaction between drugs and substances in vivo at the molecular level can significantly shorten the drug development process. This paper reviews the mechanism of PD-1/PD-L1 signaling pathway at the molecular level, as well as the research progress and obstacles of inhibitors. Besides, we analyzed the binding mode of recently reported PD-1/PD-L1 inhibitors with PD-1 or PD-L1 protein in detail in order to provide ideas for the development of PD-1/PD-L1 inhibitors.

Photoelectrochemical immunosensor for HER2 detection based on BiVO4-Bi2S3 heterojunction as photoactive material and CdS as signal probe.

A sandwiched photoelectrochemical (PEC) sensor was developed for sensitive detection of human epidermal growth factor receptor 2 (HER2) based on BiVO4-Bi2S3 heterojunction as the photoelectric material accompanied with magnetic nanoparticles for enrichment of HER2 and CdS for signal amplification. The in situ generation of Bi2S3 on the surface of BiVO4 forming a BiVO4-Bi2S3 heterojunction is more conducive to the transit of electron-hole pairs. Antibody-modified MNs are utilized to capture and separate HER2 from samples. After forming a sandwich immune structure, under illumination, the photocurrent shows an increasing trend with the increment of HER2 concentration. The PEC immunosensor displays a good linear concentration range between 1.00 and 1.00 × 103 pg·mL-1 and a low limit of detection down to 0.680 pg·mL-1 (S/N = 3) for HER2 under a bias voltage of 0.1 V (vs. Ag/AgCl electrode). Furthermore, the sensor was successfully applied to detect HER2 in serum samples with recoveries that ranged between 96.1 and 114% with RSDs between 1.3 and 5.9%.

Efficacy of high-fidelity simulation in advanced life support training: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Simulation is an increasingly used novel method for the education of medical professionals. This study aimed to systematically review the efficacy of high-fidelity (HF) simulation compared with low-fidelity (LF) simulation or no simulation in advanced life support (ALS) training. METHODS: A comprehensive search of the PubMed, Chinese Biomedicine Database, Embase, CENTRAL, ISI, and China Knowledge Resource Integrated Database was performed to identify randomized controlled trials (RCTs) that evaluated the use of HF simulation in ALS training. Quality assessment was based on the Cochrane Handbook for Systematic Reviews of Interventions version 5.0.1. The primary outcome was the improvement of knowledge and skill performance. The secondary outcomes included the participants' confidence and satisfaction at the course conclusion, skill performance at one year, skill performance in actual resuscitation, and patient outcomes. Data were synthesized using the RevMan 5.4 software. RESULTS: Altogether, 25 RCTs with a total of 1,987 trainees were included in the meta-analysis. In the intervention group, 998 participants used HF manikins, whereas 989 participants received LF simulation-based or traditional training (classical training without simulation). Pooled data from the RCTs demonstrated a benefit in improvement of knowledge [standardized mean difference (SMD) = 0.38; 95% confidence interval (CI): 0.18-0.59, P = 0.0003, I2 = 70%] and skill performance (SMD = 0.63; 95% CI: 0.21-1.04, P = 0.003, I2 = 92%) for HF simulation when compared with LF simulation and traditional training. The subgroup analysis revealed a greater benefit in knowledge with HF simulation compared with traditional training at the course conclusion (SMD = 0.51; 95% CI: 0.20-0.83, P = 0.003, I2 = 61%). Studies measuring knowledge at three months, skill performance at one year, teamwork behaviors, participants' satisfaction and confidence demonstrated no significant benefit for HF simulation. CONCLUSIONS: Learners using HF simulation more significantly benefited from the ALS training in terms of knowledge and skill performance at the course conclusion. However, further research is necessary to enhance long-term retention of knowledge and skill in actual resuscitation and patient's outcomes.

An all-in-one strategy for municipal solid waste incineration fly ash full resource utilization by heat treatment with added kaolin.

Resourcization has become a popular research topic for the final disposal of municipal solid waste incineration fly ash (MSWI FA). However, the current research is limited to building material preparation or valuable chloride recovery, which may cause resource waste and secondary pollution. A unique process, heat treatment with the addition of kaolin (KL), was presented to achieve complete resource utilization of MSWI FA. The physical properties of ceramsite could be improved by adding KL, and dioxin removal, heavy metals, and valuable chloride separation could be achieved via sintering at 1150 °C. The separation and purification of dust carried by the flue gas during thermal treatment (secondary fly ash) was achieved via wet separation. A building ceramsite with a compressive strength of 24.8 MPa was obtained, whereas dioxin and heavy metal toxicity were far below the standard limits. Heavy metal content was enriched by 12 times, approximately 59.6%, achieved after secondary fly ash separation and purification. A heavy metal product containing 39.5% Zn, 19.1% Pb, and chloride salt containing 41.8% KCl were obtained. This showed a high potential for the developed process to separate multiple valuable elements from ashes. This novel process will further promote the development and application of harmless and resourceful technologies for MSWI FA.

Two Novel Neutral Cyclometalated Iridium(III) Complexes Based on 10,11,12,13-Tetrahydrodibenzo[a,c]phenazine for Efficient Red Electroluminescence.

Two novel neutral phosphorescent iridium(III) complexes (Ir1 and Ir2) were rationally designed and synthesized with high yields using 10,11,12,13-tetrahydrodibenzo[a,c]phenazine as the main ligand. The two complexes showed bright-red phosphorescence (625 nm for Ir1, and 620 nm for Ir2, in CH2Cl2), high-luminescence quantum efficiency (0.32 for Ir1, and 0.35 for Ir2), obvious solvatochromism and good thermostability. Then, they were used to fabricate high-efficiency red OLEDs via vacuum evaporation; the maximum current efficiency, power efficiency, and external quantum efficiency of the red devices based on Ir1 and Ir2 are 13.47/15.22 cd/A, 10.35/12.26 lm/W, and 10.08/7.48%, respectively.

A Quencher-Based Blood-Autofluorescence-Suppression Strategy Enables the Quantification of Trace Analytes in Whole Blood.

Precise quantification of trace components in whole blood via fluorescence is of great significance. However, the applicability of current fluorescent probes in whole blood is largely hindered by the strong blood autofluorescence. Here, we proposed a blood autofluorescence-suppressed sensing strategy to develop an activable fluorescent probe for quantification of trace analyte in whole blood. Based on inner filter effect, by screening fluorophores whose absorption overlapped with the emission of blood, a redshift BODIPY quencher with an absorption wavelength ranging from 600-700 nm was selected for its superior quenching efficiency and high brightness. Two 7-nitrobenzo[c] [1,2,5] oxadiazole ether groups were introduced onto the BODIPY skeleton for quenching its fluorescence and the response of H2 S, a gas signal molecule that can hardly be quantified because of its low concentration in whole blood. Such detection system shows a pretty low background signal and high signal-to-back ratio, the probe thus achieved the accurate quantification of endogenous H2 S in 20-fold dilution of whole blood samples, which is the first attempt of quantifying endogenous H2 S in whole blood. Moreover, this autofluorescence-suppressed sensing strategy could be expanded to other trace analytes detection in whole blood, which may accelerate the application of fluorescent probes in clinical blood test.

Characteristics of mesenteric adipose tissue attached to different intestinal segments and their roles in immune regulation.

Mesenteric adipose tissue (MAT) plays a critical role in the intestinal physiological ecosystems. Small and large intestines have evidently intrinsic and distinct characteristics. However, whether there exist any mesenteric differences adjacent to the small and large intestines (SMAT and LMAT) has not been properly characterized. We studied the important facets of these differences, such as morphology, gene expression, cell components, and immune regulation of MATs, to characterize the mesenteric differences. The SMAT and LMAT of mice were used for comparison of tissue morphology. Paired mesenteric samples were analyzed by RNA-seq to clarify gene expression profiles. MAT partial excision models were constructed to illustrate the immune regulation roles of MATs, and 16S-seq was applied to detect the subsequent effect on microbiota. Our data show that different segments of mesenteries have different morphological structures. SMAT not only has smaller adipocytes but also contains more fat-associated lymphoid clusters than LMAT. The gene expression profile is also discrepant between these two MATs in mice. B-cell markers were abundantly expressed in SMAT, whereas development-related genes were highly expressed in LMAT. Adipose-derived stem cells of LMAT exhibited higher adipogenic potential and lower proliferation rates than those of SMAT. In addition, SMAT and LMAT play different roles in immune regulation and subsequently affect microbiota components. Finally, our data clarified the described differences between SMAT and LMAT in humans. There were significant differences in cell morphology, gene expression profiles, cell components, biological characteristics, and immune and microbiota regulation roles between regional MATs.NEW & NOTEWORTHY Our results change the paradigm of how we regard MAT as a contiguous and homogeneous tissue to an intensely heterogeneous tissue. Appreciation of the differences between regional MATs will guide future research to investigate the specialized roles of different MATs in intestinal health and disease.

Transcriptomic and proteomic analyses uncover the drought adaption landscape of Phoebe zhennan.

BACKGROUND: Phoebe zhennan S.Lee (nanmu) is listed as a threatened tree species in China, whose growth and development, especially during the seedling stage, can be severely limited by drought. Previous studies on nanmu responses to drought stress involved physiological and biochemical analyses, while the molecular mechanisms remained unclear. Therefore, it is of great significance to carry out molecular biology research on the drought resistance of nanmu and reveal the genetic background and molecular regulation mechanism of nanmu drought resistance. RESULTS: Drought stress enhanced the soluble sugar (SS), free proline(PRO), superoxide anion (O2·-), and hydrogen peroxide (H2O2) contents as well as the peroxidase (POD) and monodehydroascorbate reductase (MDHAR) activities of nanmu. However, glutathione S-transferase (GST) activity was sensitive to drought stress. Further transcriptomic and proteomic analyses revealed the abundant members of the differentially expressed genes(DEGs) and differentially expressed proteins(DEPs) that were related to phenylpropanoid and flavonoid biosynthesis, hormone biosynthesis and signal transduction, chlorophyll metabolism, photosynthesis, and oxidation-reduction reaction, which suggested their involvement in the drought response of nanmu. These enhanced the osmotic regulation, detoxification, and enzyme-induced and non-enzyme-induced antioxidant ability of nanmu. Moreover, 52% (447/867) of proteins that were up-regulated and 34% (307/892) down-regulated ones were attributed to the increase and decrease of transcription abundance. Transcript up (TU) and protein up (PU) groups had 447 overlaps, while transcript down (TD) and protein down (PD) groups had 307 overlaps, accounting for 54% of up and 35% of down-regulated proteins. The lack of overlap between DEGs and DEPs also suggested that post-transcriptional regulation has a critical role in nanmu response to drought. CONCLUSIONS: Our research results provide significant insights into the regulatory mechanisms of drought stress in nanmu.

Feasibility of contrast-enhanced ultrasound and flank position during percutaneous nephrolithotomy in patients with no apparent hydronephrosis: a randomized controlled trial.

PURPOSE: To investigate the puncture accuracy and feasibility of contrast-enhanced ultrasound (CEUS) guided percutaneous nephrolithotomy (PCNL) in flank position for patients with no apparent hydronephrosis. METHODS: Between May 2018 and June 2020, 72 kidney stone patients with no or mild hydronephrosis were randomized into two groups: a CEUS-guided PCNL group and a conventional ultrasound (US)-guided group. Patients' demographics and perioperative outcomes were compared, including the success rate of puncture via calyceal fornix, the success rate of a single-needle puncture, puncture time, operative time, postoperative hemoglobin loss, stone-free rate, incidence of complications and postoperative stay. RESULTS: The success rate of puncture via calyceal fornix for CEUS-guided group was significantly higher than that for conventional US-guided group (86.1 vs. 47.2%, p = 0.002). Patients performed with CEUS-guided PCNL required shorter renal puncture time than those guided with conventional US (36.5 s vs. 61.0 s, p < 0.001). The median postoperative hemoglobin loss in the CEUS-guided group was significantly lower than that in conventional US-guided group (2.5 vs. 14.5 g/L, p < 0.01). There was no statistically significant difference in the success rate of a single-needle puncture, operative time, stone-free rate, incidence of complications and postoperative stay between the two groups. CONCLUSION: CEUS guidance facilitates identification of the renal calyx fornix, and benefits more precise renal puncture and less hemoglobin loss in PCNL. CEUS-guided PCNL in flank position is a feasible approach to the treatment of kidney stone patients with no apparent hydronephrosis. TRIAL REGISTRATION NUMBER: ChiCTR1800015417.

Comparison of amphotericin B deoxycholate in combination with either flucytosine or fluconazole, and voriconazole plus flucytosine for the treatment of HIV-associated cryptococcal meningitis: a prospective multicenter study in China.

BACKGROUND: The most appropriate alternative to induction therapy for HIV-associated cryptococcal meningitis (CM) remains unclear when standard treatment is unavailable, inaccessible, intolerable, or ineffective. METHODS: A prospective, multi-centre cohort study was conducted to analyze the data of 156 HIV-infected patients with CM who were treated with amphotericin B deoxycholate (AmB-D) + flucytosine (5FC), voriconazole (VCZ) + 5FC, or AmB-D + Fluconazole (Flu) as induction regimens. Clinical efficacy, cumulative mortality, and adverse effects were compared among the three treatment groups. RESULTS: Fewer deaths occurred by week 4 and week 10 among patients receiving AmB-D + 5FC than among those receiving AmB-D + Flu [4 (5.1%) vs. 8 (16.0%) deaths by week 4; hazard ratio, 1.8; 95% confidence interval [CI], 1.0 to 3.3; p = 0.039; and 8 (10.3%) vs. 14 (28.0%) deaths by week 10; hazard ratio, 1.8; 95% CI, 1.1 to 2.7; p = 0.008, respectively]. AmB-D plus 5FC was found to result in significantly higher rates of cerebrospinal fluid (CSF) culture sterility (57.6% vs. 34% by week 2; 87.9% vs. 70% by week 10; p < 0.05 for both comparisons). However, the differences in CSF culture sterility and mortality between the VCZ + 5FC group and the AmB-D + 5FC group were not statistically significant. VCZ plus 5FC had a significantly advantageous effect on the incidence of new AIDS-defining illness and length of hospital stay, compared with AmB-D plus 5FC. Laboratory adverse events (grade 3 or 4), such as severe anemia, were less frequent with VCZ + 5FC use than with AmB-D combined with 5FC or Flu use. CONCLUSION: Our results suggest that AmB-D combined with 5FC remains the more efficacious induction regimen compared to AmB-D plus Flu, and that VCZ + 5FC might be a potential alternative when the standard regimen is not readily available, accessible, tolerated, or effective. CLINICAL TRIALS: Registration number, ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 .

Cryoprotective effect of antifreeze protein III on the rabbit ovary.

CONTEXT: Ovarian tissue cryopreservation is effective in preserving fertility in cancer patients who have concerns about fertility loss due to cancer treatment. However, ischemia reduces the lifespan of grafts. Microvascular transplantation of cryopreserved whole ovary may allow immediate revascularisation, but the damage incurred during the cryopreservation procedure may cause follicular depletion; hence, preventing chilling injury would help maintain ovarian function. AIM: This study was designed to investigate the beneficial effects of antifreeze protein III (AFP III) on rabbit ovary cryopreservation. METHODS: Ovaries (n =25) obtained from 5-month-old female rabbits (n =13) were frozen by slow freezing and vitrification. Cryoprotectant media were supplemented with and without 1mg/mL of AFP III. The experiment was divided into five groups: fresh control group (F), slow freezing group (S), slow freezing group with AFP III (AFP III-S), vitrification group (V) and vitrification group with AFP III (AFP III-V). All groups of ovaries were examined by histological characteristics analysis, ultrastructural analysis, apoptosis detection and follicle viability test. KEY RESULTS: With slow freezing, the normal rate of change in follicle morphology, density of stromal cells and the survival rate of follicles in the AFP III supplemented group were significantly higher than those in the non-supplemented group, and a lower oocyte apoptotic rate was shown in the AFP III supplemented group. In the vitrification groups, the normal rate of change in follicle morphology and density of stromal cells in the AFP III supplemented group were significantly higher than those in the non-supplemented group, and a lower oocyte apoptotic rate was found in the AFP III supplemented group. But there was no obvious difference in the survival rate of follicles between the two groups. There was also no significant difference in the normal rate of change in follicle morphology, the survival rate of follicles and the apoptotic rate of oocytes between the vitrification and slow freezing groups (P >0.05), but the density of stromal cells in the vitrification groups was statistically higher than that of the slow freezing group (P <0.05). CONCLUSIONS: The addition of AFP III in slow freezing and vitrification could improve the cryoprotective effect of ovaries, which was more evident in slow freezing. IMPLICATIONS: The findings of this study provide a foundation for further research on the effects of AFP III in human ovarian tissue.

Anatomical and visual outcomes of fovea-sparing internal limiting membrane peeling with or without inverted flap technique for myopic foveoschisis.

BACKGROUND: Vitrectomy and peeling of the internal limiting membrane (ILM) was an effective therapeutic approach for myopic foveoschisis with progressive visual loss. This study investigated the anatomical and visual outcomes of fovea-sparing ILM peeling with or without the inverted flap technique for patients with symptomatic myopic foveoschisis (MF). METHODS: We retrospectively reviewed the clinical data of patients with MF. Vitrectomy with fovea-sparing ILM peeling and air tamponade was performed in all patients. The primary outcome measures included best-corrected visual acuity (BCVA), mean macular thickness (MMT), and central foveal thickness (CFT). Depending on whether an inverted ILM flap technique was utilized, further subgroup comparisons between the inverted flap group and the non-inverted flap group were conducted. RESULTS: Twenty-six eyes of 22 patients were included. Fifteen eyes were underwent fovea-sparing ILM peeling without inverted ILM flap and 11 of the 26 eyes were treated with fovea-sparing ILM peeling and an inverted ILM flap technique. In the mean follow-up period of 10.74 ± 4.58 months, a significant improvement in BCVA was observed from 0.97 ± 0.45 logMAR to 0.58 ± 0.51 logMAR (P < 0.01), during which the BCVA of 20 eyes (76.92%) improved and remained stable in 5 eyes (19.23%). Moreover, a positive correlation was also found between the preoperative BCVA and the postoperative BCVA (r = 0.50, P = 0.01). At the last visit, the final MMT decreased from 492.69 ± 209.62 µm to 234.73 ± 86.09 µm, and the CFT reduced from 296.08 ± 209.22 µm to 138.31 ± 73.92 µm (all P < 0.01). A subgroup analysis found no significant differences in BCVA, MMT, or CFT between the inverted and non-inverted flap groups (all P > 0.05). CONCLUSION: Fovea-sparing ILM peeling with or without inverted flap technique resulted in favorable visual and anatomical outcomes for the treatment of MF. An important factor affecting the postoperative visual outcome was the preoperative visual acuity. Our study found no significant difference between the presence and absence of the inverted ILM flap.