Comparative transcriptomic analysis delineates adaptation strategies of Rana kukunoris toward cold stress on the Qinghai-Tibet Plateau.

BACKGROUND: Cold hardiness is fundamental for amphibians to survive during the extremely cold winter on the Qinghai-Tibet plateau. Exploring the gene regulation mechanism of freezing-tolerant Rana kukunoris could help us to understand how the frogs survive in winter. RESULTS: Transcriptome of liver and muscle of R. kukunoris collected in hibernation and spring were assisted by single molecule real-time (SMRT) sequencing technology. A total of 10,062 unigenes of R. kukunoris were obtained, and 9,924 coding sequences (CDS) were successfully annotated. Our examination of the mRNA response to whole body freezing and recover in the frogs revealed key genes concerning underlying antifreeze proteins and cryoprotectants (glucose and urea). Functional pathway analyses revealed differential regulated pathways of ribosome, energy supply, and protein metabolism which displayed a freeze-induced response and damage recover. Genes related to energy supply in the muscle of winter frogs were up-regulated compared with the muscle of spring frogs. The liver of hibernating frogs maintained modest levels of protein synthesis in the winter. In contrast, the liver underwent intensive high levels of protein synthesis and lipid catabolism to produce substantial quantity of fresh proteins and energy in spring. Differences between hibernation and spring were smaller than that between tissues, yet the physiological traits of hibernation were nevertheless passed down to active state in spring. CONCLUSIONS: Based on our comparative transcriptomic analyses, we revealed the likely adaptive mechanisms of R. kukunoris. Ultimately, our study expands genetic resources for the freezing-tolerant frogs.

Identification of Genetic Variants in Progressive Supranuclear Palsy in Southeast Asia.

BACKGROUND: Progressive supranuclear palsy (PSP) is largely a sporadic disease with few reported familial cases. Genome-wide association studies (GWAS) in sporadic PSP in Caucasian populations have identified MAPT as the most commonly associated genetic risk locus with the strongest effect size. At present there are limited data on genetic factors associated with PSP in Asian populations. OBJECTIVES: Our goal was to investigate the genetic factors associated with PSP in Southeast Asian PSP patients. METHODS: Next-generation sequencing (whole-exome, whole-genome and targeted sequencing) was performed in two Asian cohorts, comprising 177 PSP patients. RESULTS: We identified 17 pathogenic or likely pathogenic variants in 16 PSP patients (9%), eight of which were novel. The most common relevant genetic variants identified were in MAPT, GBA1, OPTN, SYNJ1, and SQSTM1. Other variants detected were in TBK1, PRNP, and ABCA7-genes that have been implicated in other neurodegenerative diseases. Eighteen patients had a positive family history, of whom two carried pathogenic MAPT variants, and one carried a likely pathogenic GBA1 variant. None of the patients had expanded repeats in C9orf72. Furthermore, we found 16 different variants of uncertain significance in 21 PSP patients in PSEN2, ABCA7, SMPD1, MAPT, ATP13A2, OPTN, SQSTM1, CYLD, and BSN. CONCLUSIONS: The genetic findings in our PSP cohorts appear to be somewhat distinct from those in Western populations, and also suggest an overlap of the genetic architecture between PSP and other neurodegenerative diseases. Further functional studies and validation in independent Asian cohorts will be useful for improving our understanding of PSP genetics and guiding genetic screening strategies in these populations. © 2024 International Parkinson and Movement Disorder Society.

What is the definition of stone dust and how does it compare with clinically insignificant residual fragments? A comprehensive review.

PURPOSE: During endoscopic stone surgery, Holmium:YAG (Ho:YAG) and Thulium Fiber Laser (TFL) technologies allow to pulverize urinary stones into fine particles, ie DUST. Yet, currently there is no consensus on the exact definition of DUST. This review aimed to define stone DUST and Clinically Insignificant Residual Fragments (CIRF). METHODS: Embase, MEDLINE (PubMed) and Cochrane databases were searched for both in vitro and in vivo articles relating to DUST and CIRF definitions, in November 2023, using keyword combinations: "dust", "stones", "urinary calculi", "urolithiasis", "residual fragments", "dusting", "fragments", "lasers" and "clinical insignificant residual fragments". RESULTS: DUST relates to the fine pulverization of urinary stones, defined in vitro as particles spontaneously floating with a sedimentation duration ≥ 2 sec and suited for aspiration through a 3.6Fr-working channel (WC) of a flexible ureteroscope (FURS). Generally, an upper size limit of 250 µm seems to agree with the definition of DUST. Ho:YAG with and without "Moses Technology", TFL and the recent pulsed-Thulium:YAG (pTm:YAG) can produce DUST, but no perioperative technology can currently measure DUST size. The TFL and pTm:YAG achieve better dusting compared to Ho:YAG. CIRF relates to residual fragments (RF) that are not associated with imminent stone-related events: loin pain, acute renal colic, medical or interventional retreatment. CIRF size definition has decreased from older studies based on Shock Wave Lithotripsy (SWL) (≤ 4 mm) to more recent studies based on FURS (≤ 2 mm) and Percutaneous Nephrolithotomy(PCNL) (≤ 4 mm). RF ≤ 2 mm are associated with lower stone recurrence, regrowth and clinical events rates. While CIRF should be evaluated postoperatively using Non-Contrast Computed Tomography(NCCT), there is no consensus on the best diagnostic modality to assess the presence and quantity of DUST. CONCLUSION: DUST and CIRF refer to independent entities. DUST is defined in vitro by a stone particle size criteria of 250 µm, translating clinically as particles able to be fully aspirated through a 3.6Fr-WC without blockage. CIRF relates to ≤ 2 RF on postoperative NCCT.

Steady-state versus burst lasing techniques for thulium fiber laser.

OBJECTIVE: To evaluate the stone ablation rate and direct thermal damage from thulium fiber laser (TFL) lithotripsy using continuous (C) and burst (B) lasing techniques on an in vitro ureteral model. METHODS: The TFL Drive (Coloplast, Humlebaek, Denmark) was used in an in vitro saline-submerged ureteral model. Ten participants, including five junior and five experienced urologists, conducted the experimental setup with 7 different settings comparing two lasing techniques: steady-state lasing (0.5 J/10 Hz = 5W for 300 s and 0.5 J/20 Hz = 10W for 150 s) and burst, intermittent 5 s on/off lasing (0.5 J/20 Hz, 0.5 J/30 Hz, 0.5 J/60 Hz, 0.1 J/200 Hz, and 0.05 J/400 Hz) with a target cumulative energy of 1500 J using cubic 125 mm3 phantom BegoStonesTM. Ureteral damage was graded 1-3 based on the severity of burns and holes observed on the surface of the ureteral model. RESULTS: The were no significant differences in stone ablation mass neither between C and B lasing techniques, nor between expertise levels. At C lasing technique had only mild ureteral lesions with no significant differences between expertise levels (p: 0.97) or laser settings (p: 0.71). At B lasing technique, different types of thermal lesions were found with no expertise (p: 0.11) or setting (p: 0.83) differences. However, B laser setting had higher grade direct thermal lesions than C (p: 0.048). CONCLUSION: Regarding efficacy, C and B lasing techniques achieve comparable stone ablation rates. Safety-wise, B lasing mode showed higher grade of direct thermal lesions. These results should be further investigated to verify which of the lasing mode is the safest in vivo. Until then and unless proven otherwise, a C mode with low frequency should be recommended to avoid ureteral wall lesions.

Illumination matters Part III: Impact of light obstruction on illuminance from flexible ureteroscopes - a comparative PEARLS analysis.

PURPOSE: Artifacts from poor ureteroscopes' light design with shadowing and dark areas in the field of view have been reported. The aim was to quantify effects of light obstruction in a kidney calyx model. METHODS: We evaluated a series of contemporary flexible ureteroscopes including the Storz Flex-Xc and Flex-X2s, Olympus V3 and P7, Pusen 7.5F and 9.2F, as well as OTU Wiscope using an enclosed 3D-printed pink in vitro kidney calyx model submerged in saline, where the field of light was intentionally partially obstructed alternatively at 12, 3, 6, and 9 o'clock. A color spectrometer was used for illuminance measurements at a 45° opening position in the background of the model. RESULTS: Overall and mean background illuminance for each obstructive situation were significantly different between scopes for both 50% and 100% brightness settings (ANOVA p < 0.001). At 50% brightness setting, almost all scopes had their highest and lowest background illuminance with the 6 o'clock and 3 o'clock obstructive situation, respectively. At 100% brightness setting, these became 6 o'clock and 12 o'clock obstructive situations. Considering each obstructive situation individually, the Flex-Xc was consistently the scope with highest background illuminance and the Pusen 7.5F the lowest. Background illuminance for each obstructive situation varied significantly for each scope individually, with the greatest range of variability for Pusen 7.5F and V3. CONCLUSIONS: Illuminance performance of ureteroscopes within an obstructed calyx model differ significantly for various obstructive situations. Urologists should be aware of this to help guide their choice of ureteroscope.

Illumination matters Part II: advanced comparative analysis of flexible ureteroscopes in a kidney model by PEARLS.

PURPOSE: The aim of the study was to evaluate illumination properties in an in-vitro kidney calyx model in saline. DESIGN AND METHODS: We evaluated a series of contemporary flexible ureteroscopes including the Storz Flex-Xc and Flex-X2s, Olympus V3 and P7, Pusen 7.5F and 9.2F, as well as OTU WiScope using a 3D-printed closed pink kidney calyx model, submerged in saline. A spectrometer was used for illuminance and color temperature measurements at different openings located at center (direct light), 45° (direct and indirect light) and 90°(indirect light) to the axis of the scope. RESULTS: Maximum illuminance was at the center opening for all scopes (range: 284 to 12,058 lx at 50% brightness and 454 to 11,871 lx at 100% brightness settings). The scope with the highest center illuminance (Flex-Xc) was 26 times superior to the scope with the lowest illuminance (Pusen 7.5Fr) at 100% brightness setting. For each scope, there was a peripheral illuminance drop ranging from - 43 to - 92% at 50% brightness and - 43% to - 88% at 100% brightness settings, respectively (all p < 0.01). Highest drop was for the P7 and the Pusen 9.2F. All scopes had illuminance skew, except the V3. All scopes had a warm color temperature. CONCLUSION: Illumination properties vary between ureteroscopes in an enclosed cavity in saline, and differs at center vs 45° and 90° positions within scopes. Peripheral illuminance drop can be as high as - 92%, which is undesirable. This may affect the choice of ureteroscope and light brightness settings used in surgery by urologists.

Illumination matters part IV: blackout and whiteout in flexible ureteroscopy - first report on a phenomenon observed by PEARLS.

PURPOSE: To date, no study has evaluated effects of varying brightness settings on image quality from flexible ureteroscopes submerged in saline. The aim was to evaluate blackout and whiteout occurrences in an in-vitro kidney calyx model. MATERIAL AND METHODS: We evaluated a series of contemporary flexible ureteroscopes including the Storz Flex-Xc and Flex-X2s, Olympus V3 and P7, Pusen 7.5F and 9.2F, as well as OTU WiScope using a 3D-printed enclosed pink in-vitro kidney calyx model submerged in saline. Endoscopic images were captured with ureteroscope tip placed at 5 mm,10 mm and 20 mm distances. The complete range of brightness settings and video capture modes were evaluated for each scope. Distribution of brightness on a grayscale histogram of images was analyzed (scale range 0 to 255). Blackout and whiteout were defined as median histogram ranges from 0 to 35 and 220 to 255, respectively (monitor image too dark or too bright for the human eye, respectively). RESULTS: Blackout occurred with the P7, Pusen 7.5F, 9.2F and WiScope at all distances, and V3 at 20 mm - with lowest brightness settings. Whiteout occurred with Flex-X2s, V3 and P7 at 5 mm and 10 mm, as well as with V3 and P7 at 20 mm - mostly with highest brightness settings. The Flex-Xc had neither blackout nor whiteout at all settings and distances. CONCLUSION: Blackout or whiteout of images is an undesirable property that was found for several scopes, possibly impacting diagnostic and therapeutic purposes during ureteroscopy. These observations form a guide to impact a urologist's choice of instruments and settings.

Illumination matters part I: comparative analysis of light sources and illumination in flexible ureteroscopy-fundamental findings from a PEARLS analysis.

PURPOSE: Illumination characteristics of flexible ureteroscopes have been evaluated in air, but not in saline, the native operative medium for endourology. The aim was to evaluate light properties of contemporary ureteroscopes in air versus saline, light distribution analysis, and color temperature. METHODS: We evaluated the Storz Flex-Xc and Flex-X2s, Olympus V3 and P7, Pusen 7.5F and 9.2F, and OTU WiScope using a 3D printed black target board in-vitro model submerged in saline. A spectrometer was used for lux and color temperature measurements at different opening locations. RESULTS: Illuminance was higher in saline compared to air (5679 vs. 5205 lx with Flex-Xc, p = 0.02). Illuminance in saline differed between ureteroscopes (ANOVA p < 0.001), with highest for the Flex-Xc at 100% brightness setting (5679 lx), followed by Pusen 9.2F (5280 lx), Flex-X2s (4613 lx), P7 (4371 lx), V3 (2374 lx), WiScope (582 lx) and finally Pusen 7.5F (255 lx). The same ranking was found at 50% brightness setting, with the highest ureteroscope illuminance value 34 times that of the scope with lowest illuminance. Most scopes had maximum illuminance off center, with skewness. Three scopes had two light sources, with one light source for all other scopes. Inter-scope comparisons revealed significant differences of color temperature (ANOVA p < 0.001). CONCLUSION: The study demonstrates the presence of inhomogeneous light spread as well as large differences in illumination properties of ureteroscopes, possibly impacting on the performance of individual scopes in vivo. Additionally, the study suggests that future studies on illumination characteristics of flexible ureteroscopes should ideally be done in saline, and no longer in air.

Simple and field-adapted species identification of biological specimens combining multiplex multienzyme isothermal rapid amplification, lateral flow dipsticks, and universal primers for initial rapid screening without standard PCR laboratory.

Species identification of biological specimens can provide the valuable clues and accelerate the speed of prosecution material processing for forensic investigation, especially when the case scene is inaccessible and the physical evidence is cumbersome. Thus, establishing a rapid, simple, and field-adapted species identification method is crucial for forensic scientists, particularly as first-line technology at the crime scene for initial rapid screening. In this study, we established a new field-adapted species identification method by combining multiplex multienzyme isothermal rapid amplification (MIRA), lateral flow dipstick (LFD) system, and universal primers. Universal primers targeting COX I and COX II genes were used in multiplex MIRA-LFD system for seven species identification, and a dedicated MIRA-LFD system primer targeting CYT B gene was used to detect the human material. DNA extraction was performed by collecting DNA directly from the centrifuged supernatant. Our study found that the entire amplification process took only 15 min at 37 °C and the results of LFDs could be visually observed after 10 min. The detection sensitivity of human material could reach 10 pg, which is equivalent to the detection of single cell. Different common animal samples mixed at the ratio of 1 ng:1 ng, 10 ng:1 ng, and 1 ng:10 ng could be detected successfully. Furthermore, the damaged and degraded samples could also be detected. Therefore, the convenient, feasible, and rapid approach for species identification is suitable for popularization as first-line technology at the crime scene for initial rapid screening and provides a great convenient for forensic application.

Effects of warming at embryonic and larval stages on tadpole fitness in high-altitude Rana kukunoris.

Global warming may affect the early developmental stages of high-altitude amphibians, thereby influencing their later fitness. Yet, this has been largely unexplored. To investigate whether and how the temperatures experienced by embryonic and larval stages affect their fitness at later developmental stages, we designed two experiments in which the embryos and larvae were treated with three temperatures (24, 18 and 12 °C), respectively. Then, the life history traits of the tadpoles during the metamorphotic climax in all treatments were evaluated, including growth rate, survival rate, morphology, thermal physiology, swimming performance, standard metabolic rate (SMR), oxidative and antioxidative system, and metabolic enzyme activities. The results revealed that elevated temperature accelerated metamorphosis but decreased body size at metamorphosis. Additionally, warming during the embryonic and larval stages decreased the thermal tolerance range and induced increased oxidative stress. Furthermore, high embryonic temperature significantly decreased the hatching success, but had no significant effect on swimming performance and SMR. Warming during larval periods was harmful to the survival and swimming performance of tadpoles. The effect size analysis revealed that the negative impacts of embryonic temperature on certain physiological traits, such as growth and development, survival and swimming performance, were more pronounced than those of larval temperature. Our results highlight the necessity for particular attention to be paid to the early stages of amphibians, notably the embryonic stages when evaluating the impact of global warming on their survival.

Quantitative imaging for predicting hematoma expansion in intracerebral hemorrhage: A multimodel comparison.

BACKGROUND: Several studies report that radiomics provides additional information for predicting hematoma expansion in intracerebral hemorrhage (ICH). However, the comparison of diagnostic performance of radiomics for predicting revised hematoma expansion (RHE) remains unclear. METHODS: The cohort comprised 312 consecutive patients with ICH. A total of 1106 radiomics features from seven categories were extracted using Python software. Support vector machines achieved the best performance in both the training and validation datasets. Clinical factors models were constructed to predict RHE. Receiver operating characteristic curve analysis was used to assess the abilities of non-contrast computed tomography (NCCT) signs, radiomics features, and combined models to predict RHE. RESULTS: We finally selected the top 21 features for predicting RHE. After univariate analysis, 4 clinical factors and 5 NCCT signs were selected for inclusion in the prediction models. In the training and validation dataset, radiomics features had a higher predictive value for RHE (AUC = 0.83) than a single NCCT sign and expansion-prone hematoma. The combined prediction model including radiomics features, clinical factors, and NCCT signs achieved higher predictive performances for RHE (AUC = 0.88) than other combined models. CONCLUSIONS: NCCT radiomics features have a good degree of discrimination for predicting RHE in ICH patients. Combined prediction models that include quantitative imaging significantly improve the prediction of RHE, which may assist in the risk stratification of ICH patients for anti-expansion treatments.

[Analysis and prospect of correlation between relative molecular weight and efficacy of polysaccharides from medicinal plant resources].

Polysaccharides from medicinal plant resources are a kind of polymers extracted from medicinal plants. They are complex long chains formed by different monosaccharides connected via glucosidic bonds. These polysaccharides usually have straight chain and branched chain structures, and their relative molecular weight changes greatly. Modern studies have shown that the biological activi-ty of polysaccharides from medicinal plant resources is closely related to their relative molecular weight. This paper first reviewed the preparation and detection methods of polysaccharides from medicinal plant resources with different relative molecular weights. Then, the paper summarized and analyzed the general experience of the correlation between efficacy and relative molecular weight of polysaccharides from medicinal plant resources with different molecular weights. It was considered that polysaccharides with large relative molecular weights(>100 kDa) play a leading role in immune regulation. Polysaccharides with medium relative molecular weights(10-100 kDa) play a leading role in immune regulation and the protection of the liver. Polysaccharides with small relative molecular weights(<10 kDa) play a leading role in anti-oxidation, regulation of intestinal flora, regulation of blood glucose and lipids, anti-fatigue, and the protection of nerves. Therefore, precise development of polysaccharides from medicinal plant resources based on relative molecular weight is expected to improve their biological activity and application value.

SigB modulates expression of novel SigB regulon members via Bc1009 in non-stressed and heat-stressed cells revealing its alternative roles in Bacillus cereus.

BACKGROUND: The Bacillus cereus Sigma B (SigB) dependent general stress response is activated via the two-component RsbKY system, which involves a phosphate transfer from RsbK to RsbY. It has been hypothesized that the Hpr-like phosphocarrier protein (Bc1009) encoded by bc1009 in the SigB gene cluster may play a role in this transfer, thereby acting as a regulator of SigB activation. Alternatively, Bc1009 may be involved in the activation of a subset of SigB regulon members. RESULTS: We first investigated the potential role of bc1009 to act as a SigB regulator but ruled out this possibility as the deletion of bc1009 did not affect the expression of sigB and other SigB gene cluster members. The SigB-dependent functions of Bc1009 were further examined in B. cereus ATCC14579 via comparative proteome profiling (backed up by transcriptomics) of wt, Δbc1009 and ΔsigB deletion mutants under heat stress at 42 °C. This revealed 284 proteins displaying SigB-dependent alterations in protein expression levels in heat-stressed cells, including a subgroup of 138 proteins for which alterations were also Bc1009-dependent. Next to proteins with roles in stress defense, newly identified SigB and Bc1009-dependent proteins have roles in cell motility, signal transduction, transcription, cell wall biogenesis, and amino acid transport and metabolism. Analysis of lethal stress survival at 50 °C after pre-adaptation at 42 °C showed intermediate survival efficacy of Δbc1009 cells, highest survival of wt, and lowest survival of ΔsigB cells, respectively. Additional comparative proteome analysis of non-stressed wt and mutant cells at 30 °C revealed 96 proteins with SigB and Bc1009-dependent differences in levels: 51 were also identified under heat stress, and 45 showed significant differential expression at 30 °C. This includes proteins with roles in carbohydrate/ion transport and metabolism. Overlapping functions at 30 °C and 42 °C included proteins involved in motility, and ΔsigB and Δbc1009 cells showed reduced motility compared to wt cells in swimming assays at both temperatures. CONCLUSION: Our results extend the B. cereus SigB regulon to > 300 members, with a novel role of SigB-dependent Bc1009 in the activation of a subregulon of  > 180 members, conceivably via interactions with other transcriptional regulatory networks.

Comparative metabolomics analysis reveals high-altitude adaptations in a toad-headed viviparous lizard, Phrynocephalus vlangalii.

Extreme environmental conditions at high altitude, such as hypobaric hypoxia, low temperature, and strong UV radiation, pose a great challenge to the survival of animals. Although the mechanisms of adaptation to high-altitude environments have attracted much attention for native plateau species, the underlying metabolic regulation remains unclear. Here, we used a multi-platform metabolomic analysis to compare metabolic profiles of liver between high- and low-altitude populations of toad-headed lizards, Phrynocephalus vlangalii, from the Qinghai-Tibet Plateau. A total of 191 differential metabolites were identified, consisting of 108 up-regulated and 83 down-regulated metabolites in high-altitude lizards as compared with values for low-altitude lizards. Pathway analysis revealed that the significantly different metabolites were associated with carbohydrate metabolism, amino acid metabolism, purine metabolism, and glycerolipid metabolism. Most intermediary metabolites of glycolysis and the tricarboxylic acid cycle were not significantly altered between the two altitudes, but most free fatty acids as well as ß-hydroxybutyric acid were significantly lower in the high-altitude population. This may suggest that high-altitude lizards rely more on carbohydrates as their main energy fuel rather than lipids. Higher levels of phospholipids occurred in the liver of high-altitude populations, suggesting that membrane lipids may undergo adaptive remodeling in response to low-temperature stress at high altitude. In summary, this study demonstrates that metabolic profiles differ substantially between high- and low-altitude lizard populations, and that these differential metabolites and metabolic pathways can provide new insights to reveal mechanisms of adaptation to extreme environments at high altitude.

Pulsed thulium:YAG laser-ready to dust all urinary stone composition types? Results from a PEARLS analysis.

PURPOSE: To evaluate whether stone dust can be obtained from all prevailing stone composition types using the novel pulsed thulium:YAG (p-Tm:YAG), including analysis of stone particle size after lithotripsy. METHODS: Human urinary stones of 7 different compositions were subjected to in vitro lithotripsy using a p-Tm:YAG laser with 270 µm silica core fibers (Thulio®, Dornier MedTech GmbH®, Wessling, Germany). A cumulative energy of 1000 J was applied to each stone using one of three laser settings: 0.1 J × 100 Hz, 0.4 J × 25 Hz and 2.0 J × 5 Hz (average power 10 W). After lithotripsy, larger remnant fragments were separated from stone dust using a previously described method depending on the floating ability of dust particles. Fragments and dust samples were then passed through laboratory sieves to evaluate stone particle count according to a semiquantitative analysis relying on a previous definition of stone dust (i.e., stone particles ≤ 250 µm). RESULTS: The p-Tm:YAG laser was able to produce stone dust from lithotripsy up to measured smallest mesh size of 63 µm in all seven stone composition types. Notably, all dust samples from all seven stone types and with all three laser settings had high counts of particles in the size range agreeing with the definition stone dust, i.e., ≤ 250 µm. CONCLUSION: This is the first study in the literature proving the p-Tm:YAG laser capable of dusting all prevailing human urinary stone compositions, with production of dust particles ≤ 250 µm. These findings are pivotal for the broader future implementation of the p-Tm:YAG in clinical routine.

Pulsed Thulium:YAG laser - What is the lithotripsy ablation efficiency for stone dust from human urinary stones? Results from an in vitro PEARLS study.

BACKGROUND: The novel pulsed thulium:yttrium-aluminum-garnet (p-Tm:YAG) laser was recently introduced. Current studies present promising p-Tm:YAG ablation efficiency, although all are based on non-human stone models or with unknown stone composition. The present study aimed to evaluate p-Tm:YAG ablation efficiency for stone dust from human urinary stones of known compositions. METHODS: Calcium oxalate monohydrate (COM) and uric acid (UA) stones were subjected to lithotripsy in vitro using a p-Tm:YAG laser generator (Thulio®, Dornier MedTech GmbH, Germany). 200 J was applied at 0.1 J × 100 Hz, 0.4 J × 25 Hz or 2.0 J × 5 Hz (average 10W). Ablated stone dust mass was calculated from weight difference between pre-lithotripsy stone and post-lithotripsy fragments > 250 µm. Estimated ablated volume was calculated using prior known stone densities (COM: 2.04 mg/mm3, UA: 1.55 mg/mm3). RESULTS: Mean ablation mass efficiency was 0.04, 0.06, 0.07 mg/J (COM) and 0.04, 0.05, 0.06 mg/J (UA) for each laser setting, respectively. This translated to 0.021, 0.029, 0.034 mm3/J (COM) and 0.026, 0.030, 0.039 mm3/J (UA). Mean energy consumption was 26, 18, 17 J/mg (COM) and 32, 23, 17 J/mg (UA). This translated to 53, 37, 34 J/mm3 (COM) and 50, 36, 26 J/mm3 (UA). There were no statistically significant differences for laser settings or stone types (all p > 0.05). CONCLUSION: To our knowledge, this is the first study showing ablation efficiency of the p-Tm:YAG laser for stone dust from human urinary stones of known compositions. The p-Tm:YAG seems to ablate COM and UA equally well, with no statistically significant differences between differing laser settings.

Impact of body size on efficacy of high-dose dual therapy for Helicobacter pylori eradication.

BACKGROUND: High-dose dual therapy (HDDT) is an emerging and promising therapeutic regime for Helicobacter pylori (H. pylori) eradication. However, the pharmacokinetics of the components of HDDT, amoxicillin and proton pump inhibitor, are likely to be affected by body size. In this study, we aimed to find out the impact of body size on the efficacy of HDDT. METHODS: We collected the medical data of 385 treatment-naive patients infected with H. pylori who received HDDT (esomeprazole 20 mg and amoxicillin 750 mg four times daily) for 14 days from July 2020 to December 2021. The associations among the eradication efficacy, adverse events, and variables (sex, age, height, body weight, body mass index (BMI), body surface area (BSA), smoking, drinking, etc.) were analyzed respectively in our study. Among these factors, continuous variables were classified into categorical variables using the cut-off values which were calculated by receiver operating characteristic analysis. RESULTS: The eradication rate of HDDT was 89.9%. There were 55 (14.3%) patients who occurred adverse events during the treatment. Patients with height <170.5 cm, body weight <60.5 kg, BMI <20.55 kg/m2 , BSA <1.69 m2 had a higher eradication rate (92.1% vs. 84.0%, 93.1% vs. 86.8%, 96.0% vs. 87.8%, 93.4% vs. 84.8%, all p < .05). The multivariate analysis showed that BSA ≥1.69 m2 (OR 2.53, 95% CI: 1.28-4.99, p = .007) was the only independent predictor of eradication failure. CONCLUSION: HDDT could achieve better eradication efficacy in patients with small BSA. Clinicians should be aware of the impact of BSA on the H. pylori eradication rate and pay more attention to patients with large BSA.

[Discussion on discipline of herbalism].

Since the emergence of the term "materia medica", scholars have proposed different opinions on its concept. This term has been used to refer to traditional Chinese medicines, or medical books, or traditional pharmacology. Due to the differences in the concept of materia medica, scholars also have controversies about the concept of herbalism. Herbalism is usually understood as traditional Chinese pharmacology. After years of evolution, the term "herbalism" has now possessed the characteristics of an independent discipline, which can be defined as an applied basic discipline that comprehensively utilizes traditional and modern technological methods to study the formation, development, and changes of traditional pharmacology and reveal the basic theories and application laws of traditional medicine. At present, the research content of herbalism mainly includes three aspects: materia medica history, materia medica literature, and traditional pharmacology. This study explores the disciplinary concepts and main research content of herbalism based on a systematic review of the literature about the concepts of materia medica and herbalism, with the aim of attracting more attention to promote the establishment and development of the discipline of herbalism.

Glucocerebrosidase (GBA) gene variants in a multi-ethnic Asian cohort with Parkinson's disease: mutational spectrum and clinical features.

GBA variants are associated with increased risk and earlier onset of Parkinson's disease (PD), and more rapid disease progression especially with "severe" variants typified by p.L483P. GBA mutation screening studies from South-East Asia, with > 650 million inhabitants of diverse ancestries, are very limited. We investigated the spectrum of GBA variants, and associated clinico-demographic features, in a multi-ethnic PD cohort in Malaysia. Patients (n = 496) were recruited from seven centres, primarily of Chinese (45%), Malay (37%), and Indian (13%) ethnicities. All GBA coding exons were screened using a next-generation sequencing-based PD gene panel and verified with Sanger sequencing. We identified 14 heterozygous GBA alleles consisting of altogether 17 missense variants (8 classified as pathogenic or likely pathogenic for PD) in 25 (5.0%) patients, with a substantially higher yield among early (< 50 years) vs. late-onset patients across all three ethnicities (9.1-13.2% vs. 1.0-3.2%). The most common variant was p.L483P (including RecNciI, n = 11, 2.2%), detected in all three ethnicities. Three novel variants/recombinant alleles of uncertain significance were found; p.P71L, p.L411P, and p.L15S(;)S16G(;)I20V. The common European risk variants, p.E365K, p.T408M, and p.N409S, were not detected. A severe disease course was noted in the majority of GBA-variant carriers, across a range of detected variants. We report a potentially novel observation of spine posture abnormalities in GBA-variant carriers. This represents the largest study on GBA variation from South-East Asia, and highlights that these populations, especially those with EOPD, would be relevant for studies including clinical trials targeting GBA pathways.

Bromodomain-containing protein 9 promotes hepatocellular carcinoma progression via activating the Wnt/ß-catenin signaling pathway.

BACKGROUND: Epigenetic dysregulation participates in the initiation and progression of hepatocellular carcinoma (HCC). Bromodomain-containing protein 9 (BRD9) can identify acetylated lysine residues, contributing to several cancers. The function and molecular mechanism of BRD9 in HCC remain poorly understood. METHODS: BRD9 levels in tissues and cells of HCC and normal liver were evaluated using bioinformatic analysis, real-time PCR, and western blot. BRD9's association with clinical outcomes was investigated via survival analyses. Biological behaviors and pathways related to BRD9 were predicted using gene set enrichment analysis. BRD9's role in proliferation was verified via cell counting kit 8, colony formation, and 5-Ethynyl-2'-deoxyuridine assays. Its role in the cell cycle and apoptosis was assessed using flow cytometry. The role of BRD9 in vivo was investigated using xenograft tumor models. A rescue assay was performed to investigate the molecular mechanism of BRD9. RESULTS: BRD9 was markedly upregulated in HCC and higher BRD9 expression was associated with higher grade, advanced stage, greater tumor size, and poorer prognosis. BRD9 overexpression enhanced cell proliferation, cell cycle progress, but impeded cell apoptosis. BRD9 downregulation had the opposite effects. In vivo, BRD9 promoted xenograft tumor growth. Mechanistically, BRD9 activated Wnt/ß-catenin signaling, obstruction of which abrogated BRD9-mediated tumorigenesis. CONCLUSION: Increased BRD9 in HCC correlated with poor prognosis, which functioned via activating Wnt/ß-catenin signaling. Thus, BRD9 might be a promising biomarker and therapeutic target for patients with HCC.