Epithelial Na+ Channel Activation after Bile Duct Ligation with Mineralocorticoid Receptor Blockade.

BACKGROUND: Sodium and fluid retention in liver disease are classically thought to result from reduced effective circulating volume and stimulation of the renin-angiotensin-aldosterone system (RAAS). However, evidence of fluid retention in patients without RAAS activation suggests the involvement of additional mechanisms. In vitro, bile acids activate the epithelial Na+ channel (ENaC) found in the aldosterone-sensitive distal nephron. If this occurs in vivo, ENaC may become activated in liver disease even with antagonism of aldosterone signaling. METHODS: To test this, we performed bile duct ligation to induce liver disease and increase circulating bile acids in mice given spironolactone to antagonize aldosterone signaling. We analyzed effects on blood, urine and body composition. We also determined the effects of taurocholic acid, a primary conjugated bile acid elevated in liver disease, on ion fluxes in microperfused rabbit collecting ducts. RESULTS: Bile duct ligation increased benzamil-sensitive natriuresis compared to sham, indicating ENaC activation. These effects were not explained by effects on ENaC expression, cleavage, or localization. Bile duct ligated mice also gained significantly more fluid than sham-operated animals. Blocking ENaC reversed fluid gains in bile duct ligated mice but had no effect in shams. In dissected collecting ducts from rabbits, which express ENaC, taurocholic acid stimulated net Na+ absorption. CONCLUSIONS: Our results provide experimental evidence for a novel aldosterone-independent mechanism for sodium and fluid retention in liver disease.

SGLT2-independent effects of canagliflozin on NHE3 and mitochondrial complex I activity inhibit proximal tubule fluid transport and albumin uptake.

Beyond glycemic control, SGLT2 inhibitors (SGLT2is) have protective effects on cardiorenal function. Renoprotection has been suggested to involve inhibition of NHE3 leading to reduced ATP-dependent tubular workload and mitochondrial oxygen consumption. NHE3 activity is also important for regulation of endosomal pH, but the effects of SGLT2i on endocytosis are unknown. We used a highly differentiated cell culture model of proximal tubule (PT) cells to determine the direct effects of SGLT2i on Na+-dependent fluid transport and endocytic uptake in this nephron segment. Strikingly, canagliflozin but not empagliflozin reduced fluid transport across cell monolayers and dramatically inhibited endocytic uptake of albumin. These effects were independent of glucose and occurred at clinically relevant concentrations of drug. Canagliflozin acutely inhibited surface NHE3 activity, consistent with a direct effect, but did not affect endosomal pH or NHE3 phosphorylation. In addition, canagliflozin rapidly and selectively inhibited mitochondrial complex I activity. Inhibition of mitochondrial complex I by metformin recapitulated the effects of canagliflozin on endocytosis and fluid transport, whereas modulation of downstream effectors AMPK and mTOR did not. Mice given a single dose of canagliflozin excreted twice as much urine over 24 h compared with empagliflozin-treated mice despite similar water intake. We conclude that canagliflozin selectively suppresses Na+-dependent fluid transport and albumin uptake in PT cells via direct inhibition of NHE3 and of mitochondrial function upstream of the AMPK/mTOR axis. These additional targets of canagliflozin contribute significantly to reduced PT Na+-dependent fluid transport in vivo.NEW & NOTEWORTHY Reduced NHE3-mediated Na+ transport has been suggested to underlie the cardiorenal protection provided by SGLT2 inhibitors. We found that canagliflozin, but not empagliflozin, reduced NHE3-dependent fluid transport and endocytic uptake in cultured proximal tubule cells. These effects were independent of SGLT2 activity and resulted from inhibition of mitochondrial complex I and NHE3. Studies in mice are consistent with greater effects of canagliflozin versus empagliflozin on fluid transport. Our data suggest that these selective effects of canagliflozin contribute to reduced Na+-dependent transport in proximal tubule cells.

A distributed data processing scheme based on Hadoop for synchrotron radiation experiments.

With the development of synchrotron radiation sources and high-frame-rate detectors, the amount of experimental data collected at synchrotron radiation beamlines has increased exponentially. As a result, data processing for synchrotron radiation experiments has entered the era of big data. It is becoming increasingly important for beamlines to have the capability to process large-scale data in parallel to keep up with the rapid growth of data. Currently, there is no set of data processing solutions based on the big data technology framework for beamlines. Apache Hadoop is a widely used distributed system architecture for solving the problem of massive data storage and computation. This paper presents a set of distributed data processing schemes for beamlines with experimental data using Hadoop. The Hadoop Distributed File System is utilized as the distributed file storage system, and Hadoop YARN serves as the resource scheduler for the distributed computing cluster. A distributed data processing pipeline that can carry out massively parallel computation is designed and developed using Hadoop Spark. The entire data processing platform adopts a distributed microservice architecture, which makes the system easy to expand, reduces module coupling and improves reliability.

High-speed k-linear swept laser using acousto-optic deflectors with Doppler shift compensation for optical coherence tomography.

Swept laser based on the acousto-optic deflector (AOD) is a promising swept source in optical coherence tomography (OCT) applications for its high wavenumber linear sweep without mechanical motion. However, the poor coherence length and the elongated cavity of the laser imposed limitations on the acquisition of high-quality images with adequate imaging depth and high imaging speed. In this Letter, we demonstrate a compact high-speed wavenumber linear swept laser based on AOD using Doppler shift compensation, achieving a high linearity of Pearson's R of 0.999991, a duty cycle of ∼100%, an extended coherence length of 5.7 mm, an output power of 18 mW, and excellent phase stability at a sweep speed of 500 kHz. OCT structural images with a system sensitivity of 103.2 dB and OCT angiography (OCTA) of human palm in vivo have been successfully performed, serving as a compelling demonstration of the excellent performance of this swept laser. We believe that the proposed laser will be of high potential in various clinical and industrial applications in the future.

Retinoic acid released from self-assembling peptide activates cardiomyocyte proliferation and enhances repair of infarcted myocardium.

The limited cardiomyocyte proliferation is insufficient for repair of the myocardium. Therefore, activating cardiomyocyte proliferation might be a reasonable option for myocardial regeneration. Here, we investigated effect of retinoic acid (RA) on inducing adult cardiomyocyte proliferation and assessed efficacy of self-assembling peptide (SAP)-released RA in activating regeneration of the infarcted myocardium. Effect of RA on inducing cardiomyocyte proliferation was examined with the isolated cardiomyocytes. Expression of the cell cycle-associated genes and paracrine factors in the infarcted myocardium was examined at one week after treatment with SAP-carried RA. Cardiomyocyte proliferation, myocardial regeneration and improvement of cardiac function were assessed at four weeks after treatment. In the adult rat myocardium, expression of RA synthetase gene Raldh2 and RA concentration were decreased significantly. After treatment with RA, the proliferated cardiomyocytes were increased. The formulated SAP could sustainedly release RA. After treatment with SAP-carried RA, expression of the pro-proliferative genes in cell cycle and paracrine factors in the infarcted myocardium were up-regulated. Myocardial regeneration was enhanced, and cardiac function was improved significantly. These results demonstrate that RA can induce adult cardiomyocytes to proliferate effectively. The sustained release of RA with SAP is a promise strategy to enhance repair of the infarcted myocardium.

Animal models of heart failure with preserved ejection fraction (HFpEF): from metabolic pathobiology to drug discovery.

Heart failure (HF) with preserved ejection fraction (HFpEF) is currently a preeminent challenge for cardiovascular medicine. It has a poor prognosis, increasing mortality, and is escalating in prevalence worldwide. Despite accounting for over 50% of all HF patients, the mechanistic underpinnings driving HFpEF are poorly understood, thus impeding the discovery and development of mechanism-based therapies. HFpEF is a disease syndrome driven by diverse comorbidities, including hypertension, diabetes and obesity, pulmonary hypertension, aging, and atrial fibrillation. There is a lack of high-fidelity animal models that faithfully recapitulate the HFpEF phenotype, owing primarily to the disease heterogeneity, which has hampered our understanding of the complex pathophysiology of HFpEF. This review provides an updated overview of the currently available animal models of HFpEF and discusses their characteristics from the perspective of energy metabolism. Interventional strategies for efficiently utilizing energy substrates in preclinical HFpEF models are also discussed.

Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days.

BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

A meta-analysis for prevalence of infectious laryngotracheitis in chickens in mainland China in 1981-2022.

BACKGROUND: Infectious laryngotracheitis (ILT) is a highly infectious upper respiratory tract disease of chickens caused by infectious laryngotracheitis virus or Gallid herpesvirus 1 (GaHV-1). ILT is an important respiratory disease of chickens and annually causes significant economic losses in the chicken industry. Although numerous relevant studies have been published, the overall prevalence of ILT infection among chicken in mainland China is still unknown, and associated risk factors need to be evaluated to establish preventive measures. RESULTS: The present study reviewed the literature on the prevalence of ILT in chickens in China as of December 20, 2022, retrieved from six databases-CNKI, Wanfang, VIP, PubMed, Web of Science, and ScienceDirect-were used to retrieve relevant studies published between January 1, 1981 and December 20, 2022. The literature quality of studies was assessed, and 20 studies with a total of 108,587 samples were included in the meta-analysis. Results of the meta-analysis showed that the overall prevalence of ILT was 10% (95% confidence interval: 8 -12%) through the random-effects model, which showed high heterogeneity, I2 = 99.4%. Further subgroup analyses showed that the prevalence of ILT decreased over time; furthermore, the prevalence in Northwest China was slightly lower than that in North China and South China, and the prevalence estimated using the diagnostic technique AGP was higher than that reported using other diagnostic techniques. CONCLUSIONS: ILT is prevalent to some extent in mainland China. Given that the ILT attenuated live vaccine has a certain level of virulence and the prevalence differences between regions, we recommend controlling breeding density, improving immunization programs and continuously monitoring viruses and to prevent ILT prevailing in mainland China.

Effectiveness and mechanism of action of rTMS combined with quadriceps strength training in individuals with knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Quadriceps training is necessary in function and activity of daily living for patients with knee osteoarthritis (KOA). However, it did not reduce the rate of surgical treatment for end-stage KOA in the long term. This may be related to brain structure changes and maladaptive plasticity in KOA patients. Transcranial Magnetic Stimulation (TMS) could enhance the functional connectivity of brain regions and improves maladaptive plasticity. However, the synergistic effect of the combination of the two for treat KOA is still unclear. Therefore, the purpose of this study is to investigate whether the High-Frequency rTMS combined with quadriceps strength training can improve the pain and function in KOA more effectively than quadriceps training alone and explore the mechanism of action. METHODS: This study is an assessor-blind, sham-controlled, randomized controlled trial involving 12 weeks of intervention and 6 months follow-up. 148 participants with KOA will receive usual care management and be randomized into four subgroups equally, including quadriceps strength training, high-frequency rTMS training, sham rTMS and quadriceps strength training, high-frequency rTMS and quadriceps strength training. The rehabilitation interventions will be carried out 5 days per week for a total of 12 weeks. All outcomes will be measured at baseline, 4 weeks, 8 weeks, and 12 weeks during the intervention and 1 month, 3 months and 6 months during the follow-up period. The effectiveness outcomes will be included visual analog scale, isokinetic knee muscle strength, Knee Injury and Osteoarthritis Outcome score and 36-Item Short-Form Health Survey score; The act mechanism outcomes will be included motor evoked potential, grey matter density, white matter, subcortical nuclei volumes, cortical thickness and functional connectivity by MRI. Two-way of variance with repeated measures will be used to test the group and time effect for outcome measures. DISCUSSION: The study will be the first protocol to examine whether there are synergistic effects following high-frequency rTMS combined with quadriceps strength training for treat KOA and clarify the mechanism of action. High-frequency rTMS can be added into the training program for KOA patients if it is proven effective. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300067617. Registered on Jan.13,2023.

Mode of inheritance for pesticide resistance, importance and prevalence: A review.

Pesticides remain a cornerstone in pest control, yet their extensive and irrational use also fuel the evolution of resistance. This review analyzes globally published experimental data spanning from the 1970s to 2023 to focus on how phenotypic and underlying genotypic variations are shaped during the selective response. The discussion commences with an examination of sex-linked/maternal resistance. Observations related to maternal inheritance have enriched our understanding of pesticide mode of action, notably exemplified by bifenazate. However, the predominant control of the resistant phenotype is attributed to autosomal traits, with a high prevalence of dominance and monogenic inheritance observed, also evident in field strains. This observation raises concerns regarding resistance management strategies due to their potential to accelerate the spread of resistance. The interplay between dominance levels and monogenic inheritance is further explored, with dominant traits being significantly more prevalent in polygenic inheritance. This observation may be attributed to the accumulation of enhanced metabolism. Notably, further analysis indicated that field strains exhibit a higher incidence of monogenic inheritance compared to other selected strains, aligning with established theoretical frameworks. In conclusion, the genetic architecture of resistance warrants increased research focus for its pivotal role in guiding resistance management strategies and advancing fundamental research.

Exploration of decision aids to support advance care planning: A scoping review.

BACKGROUND: Advance care planning is a process through which people communicate their goals and preferences for future medical care. Due to the complexity of the decision-making process, decision aids can assist individuals in balancing potential benefits and risks of treatment options. OBJECTIVE: While decision aids have the potential to better promote advance care planning, their characteristics, content and application effectiveness are unclear and lack systematic review. Therefore, we aimed to explore these three aspects and establish a foundation for future research. DESIGN: Scoping review. METHODS: This scoping review adheres to the framework proposed by Arksey and O'Malley and the PRISMA-ScR list. Six English-language databases were systematically searched from the time of construction until 1 December 2023. Two researchers conducted the article screening and data extraction, and the extracted data was presented in written tables and narrative summaries. RESULTS: Of the 1479 titles and abstracts, 20 studies fulfilled the inclusion criteria. Types of decision aids were employed, mainly websites and videos. Decision aid's primary components center around 11 areas, such as furnishing information, exploring treatment and care preferences. The main manifestations were a significant increase in knowledge and improved recognition of patients' target value preferences. Among the aids, websites and videos for advance care planning have relatively high content acceptability and decision-making process satisfaction, but their feasibility has yet to be tested. CONCLUSIONS: Decision aids were varied, with content focused on describing key information and exploring treatment and care preferences. Regarding application effects, the aids successfully facilitated the advance care planning process and improved the quality of participants' decisions. Overall, decision aids are efficient in improving the decision-making process for implementing advance care planning in cancer and geriatric populations. In the future, personalised decision aids should be developed based on continuous optimization of tools' quality and promoted for clinical application. REPORTING METHOD: The paper has adhered to the EQUATOR guidelines and referenced the PRISMAg-ScR checklist. NO PATIENT OR PUBLIC CONTRIBUTION: This is a review without patient and public contribution. REGISTRATION: https://doi.org/10.17605/OSF.IO/YPHKF, Open Science DOI: 10.17605/OSF.IO/YPHKF.

Complications of Injected Exogenous Growth Factor for Cosmetic Facial Rejuvenation: A Case Series and Sequential Therapy.

BACKGROUND: Exogenous growth factor presents promising soft tissue regeneration, but the complications from injectable exogenous growth factor seem to be growing. However, there is no detailed summary of complications and sequential treatment protocols. It is noted that the injection of exogenous growth factor into the soft tissue is an unreasonable or even illegal procedure, which could cause uncontrollable tissue growth and some other complications. METHODS: A total of 65 patients underwent analysis retrospectively for complications related to the injection of exogenous growth factor from 2017to 2022 at Xijing Hospital in China. Initially the symptoms mainly consisted of redness, skin temperature arisen, itching, tissue hypertrophy, localized swelling, mass, and lump, with later manifestations including ulcerations and purulent discharge. A comprehensive treatment scheme was formulated based on the location and size of the lumps as well as the type of complication. Post-treatment satisfaction was evaluated over a mean 16-month follow-up (range 6-39 months). RESULTS: A total of 65 patients participated in the treatment. Drug injection therapy was initially performed on all patients. If injections were not effective, surgical treatment (debridement/excision/liposuction) was performed. Twenty-eight patients were managed with intralesional injections alone. Patients reported improved satisfaction in 23 cases (82.14%), full symptom resolution in 3 cases (10.72%), and no improvement in 2 cases (7.14%). Surgery was required for 37 patients. Postoperative improved satisfaction was reported in 30 cases (81.08%), full symptom resolution was recorded in 4 cases (10.82%), and no improvement was seen in 3 cases (8.10%). CONCLUSIONS: This study highlights the management of complications arising from exogenous growth factor injections through the implementation of a sequential therapy approach. Specifically, this approach involves the initial administration of drug injection therapy, and if drug injection therapy proves ineffective, then surgical treatment is pursued. In conclusion, the injection of exogenous growth factors into soft tissues should be forbidden. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Detection of Ascorbic Acid by Two-Dimensional Conductive Metal-Organic Framework-Based Electrochemical Sensors.

The realization of efficient and accurate detection of biomolecules has become a key scientific issue in the field of life sciences. With the rapid development of nanotechnology, electrochemical sensors constructed from the superior physical and chemical properties of nanomaterials show faster and more accurate detection. Among nanomaterials, two-dimensional conductive MOF (2D cMOF) is considered to be a star material in electrochemical sensors due to its remarkable conductivity, high porosity, and stability. In this paper, a Cu3(HHTP)2/SPE electrochemical sensor for the detection of ascorbic acid (AA) was constructed by modifying 2D cMOF (Cu3(HHTP)2) on the surface of the screen-printed electrode (SPE). The sensor exhibited excellent catalytic activity in the detection of AA, with a lower detection limit of 2.4 µmol/L (S/N = 3) and a wide linear range of 25-1645 µmol/L. This high catalytic activity can be attributed to the abundant catalytic sites in Cu3(HHTP)2 and the rapid electron transfer between Cu+ and Cu2+, which accelerates the oxidation of AA. This work lays a foundation for the subsequent development of MOFs with special electrochemical catalytic properties and the integration of 2D cMOF into intelligent electrical analysis devices.

One-Step Construction of 1,3,4-Oxadiazoles with Anticancer Activity from Tertiary Amines via a Sequential Copper(I)-Catalyzed Oxidative Ugi/aza-Wittig Reaction.

An unparalleled copper(I)-catalyzed synthesis of 1,3,4-oxadiazoles from tertiary amines in one step has been described. The one-pot reactions involving (N-isocyanimine)triphenylphosphorane, tertiary amines, and carboxylic acids resulted in the formation of 1,3,4-oxadiazoles in moderate to good yields through a consecutive oxidative Ugi/aza-Wittig reaction, enabling the direct functionalization of sp3 C-H bonds adjacent to the nitrogen atom. This method offered several notable advantages, including ligands-free, exceptional productivity and a high functional group tolerance. The preliminary biological evaluation demonstrated that compound 4f inhibited hepatoma cells efficiently, suggesting potentially broad applications of the approach for synthesis and medicinal chemistry.

Effect of Pressure and Nonpressure Dressings on Postoperative Complications in Patients With Mixed Hemorrhoids: A Single-blind Controlled Study.

PURPOSE: To compare the clinical effects of nonpressure and pressure dressings on the postoperative complications of modified Milligan-Morgan hemorrhoidectomy. DESIGN: Randomized controlled trial. METHODS: A total of 186 patients with grade II to III mixed hemorrhoids who had been excluded from cardiovascular and cerebrovascular diseases and anorectal surgery were included and randomly assigned to the nonpressure dressings group and the pressure dressings group by random number table. The incidence of acute urinary retention and medical adhesive-related skin injury, pain, hemostatic effect, anal distension, anal edema, use of analgesics, length of hospital stay, and hospitalization costs were compared between the two groups. The Consolidated Standards of Reporting Trials checklist for randomized controlled trials was used in this study. FINDINGS: The incidence of acute urinary retention in both men and women was significantly lower in the nonpressure dressing group (relative risk [RR] = 0.20, 95% confidence interval [CI] [0.13, 0.37], P = .002); (RR = 0.47, 95% CI [0.22, 0.76], P = .015). The postoperative pain at 6 hours/18 hours/25 hours was significantly lower in the nonpressure dressing group (P < .001, P = .004 < 0.05, P = .009). The anal distension at 6 hours and the number of patients who used analgesics were significantly lower in the nonpressure dressing group (P < .001). The incidence of medical adhesive-related skin injuries was significantly lower in the nonpressure dressing group (RR = 0.061, 95% CI [0.020, 0.189], P < .001). No primary bleeding was observed in both groups. However, there were no significant differences between both groups in terms of anal edema scores, length of stay, or hospitalization expenses. No adverse events were reported in either group during the study period. CONCLUSIONS: Nonpressure dressings can effectively reduce the incidence of acute urinary retention and medical adhesion-related skin injury after surgery for grade III to IV mixed hemorrhoids. They can also safely relieve pain and distension.

[Intervention effect of narrative therapy on non-suicidal self-injury in adolescents with depressive disorder: a prospective randomized controlled study]. / å™äº‹æ²»ç–—å¯¹é’å°‘å¹´æŠ‘éƒç—‡æ‚£è€ éžè‡ªæ€æ€§è‡ªä¼¤çš„å¹²é¢„æ•ˆæžœï¼šä¸€é¡¹å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the intervention effect of narrative therapy on non-suicidal self-injury (NSSI), as well as anxiety and depression symptoms in adolescents with depressive disorder. METHODS: Sixty adolescents with depressive disorder and NSSI were randomly assigned to either the intervention group or the control group using coin flipping. The control group received conventional psychological support, while the intervention group received individual narrative therapy in addition to the conventional psychological support (twice a week, 60 minutes per session, for a total of 3 weeks). Assessment of treatment efficacy was conducted using the Adolescent Self-Harm Questionnaire, Children's Depression Inventory, and Children's Anxiety and Mood Scale before the intervention, at the end of the intervention, and one month after the intervention for both groups. RESULTS: A total of 26 adolescents in the intervention group and 29 adolescents in the control group completed the entire study. At the end of the intervention and one month after the intervention, the intervention group showed a significant reduction in the NSSI frequency score, NSSI level, anxiety score, and depression score compared to before the intervention (P<0.017). Moreover, at the end of the intervention and one month after the intervention, the intervention group exhibited significantly lower NSSI frequency score, NSSI severity score, NSSI level, anxiety score and depression score compared to the control group (P<0.05). CONCLUSIONS: Narrative therapy is effective in reducing NSSI frequency and alleviating NSSI severity, as well as anxiety and depression symptoms in adolescents with depressive disorder.

[A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020]. / 2019­2020å¹´160ä¾‹å„¿ç«¥è‚ºç‚Žé“¾çƒèŒè„‘è†œç‚Žä¸´åºŠæµè¡Œç— å­¦å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Comparative transcriptome analysis reveals candidate genes related to the sex differentiation of Schisandra chinensis.

Schisandra chinensis is a monoecious plant with unisex flowers. The fruit of S. chinensis is of high medical with economic value. The yield of S. chinensis fruit is related to the ratio of its female and male flowers. However, there is little research on its floral development and sex differentiation. To elucidate the possible mechanism for the sex differentiation of S. chinensis, we collected 18 samples of female and male flowers from three developmental stages and performed a comparative RNA-seq analysis aimed at identifying differentially expressed genes (DEGs) that may be related to sex differentiation. The results showed 936, 7179, and 6890 differentially expressed genes between female and male flowers at three developmental stages, respectively, and 466 candidate genes may play roles in sex differentiation. KEGG analysis showed genes involved in the flavonoid biosynthesis pathway and DNA replication pathway were essential for the development of female flowers. 51 MADS-box genes and 10 YABBY genes were identified in S. chinensis. The DEGs analysis indicated that MADS-box and YABBY genes were strongly related to the sex determination of S. chinensis. RT-qPCR confirmed the RNA-seq results of 20 differentially expressed genes, including three male-biased genes and 17 female-biased genes. A possible regulatory model of sex differentiation in S. chinensis was proposed according to our results. This study helps reveal the sex-differentiation mechanism of S. chinensis and lays the foundation for regulating the male-female ratio of S. chinensis in the future.

Multimodal-based machine learning strategy for accurate and non-invasive prediction of intramedullary glioma grade and mutation status of molecular markers: a retrospective study.

BACKGROUND: Determining the grade and molecular marker status of intramedullary gliomas is important for assessing treatment outcomes and prognosis. Invasive biopsy for pathology usually carries a high risk of tissue damage, especially to the spinal cord, and there are currently no non-invasive strategies to identify the pathological type of intramedullary gliomas. Therefore, this study aimed to develop a non-invasive machine learning model to assist doctors in identifying the intramedullary glioma grade and mutation status of molecular markers. METHODS: A total of 461 patients from two institutions were included, and their sagittal (SAG) and transverse (TRA) T2-weighted magnetic resonance imaging scans and clinical data were acquired preoperatively. We employed a transformer-based deep learning model to automatically segment lesions in the SAG and TRA phases and extract their radiomics features. Different feature representations were fed into the proposed neural networks and compared with those of other mainstream models. RESULTS: The dice similarity coefficients of the Swin transformer in the SAG and TRA phases were 0.8697 and 0.8738, respectively. The results demonstrated that the best performance was obtained in our proposed neural networks based on multimodal fusion (SAG-TRA-clinical) features. In the external validation cohort, the areas under the receiver operating characteristic curve for graded (WHO I-II or WHO III-IV), alpha thalassemia/mental retardation syndrome X-linked (ATRX) status, and tumor protein p53 (P53) status prediction tasks were 0.8431, 0.7622, and 0.7954, respectively. CONCLUSIONS: This study reports a novel machine learning strategy that, for the first time, is based on multimodal features to predict the ATRX and P53 mutation status and grades of intramedullary gliomas. The generalized application of these models could non-invasively provide more tumor-specific pathological information for determining the treatment and prognosis of intramedullary gliomas.

Polarization-isolated stretched-pulse mode-locked swept laser for 10.3-MHz A-line rate optical coherence tomography.

Stretched-pulse mode-locked (SPML) lasing based on a chirped fiber Bragg grating (CFBG) has proven to be a powerful method to generate wavelength-swept lasers at speeds of tens of megahertz. However, light transmitted through the CFBG may lead to undesirable laser oscillation that disrupts the mechanism of the laser active mode locking in the theta ring cavity. In this Letter, we demonstrate a simple and low-cost approach to suppress the transmitted light and achieve an effective duty cycle of ∼100% with only one CFBG and no need for intra-cavity semiconductor optical amplifier (SOA) modulation, extra-cavity optical buffering, and post amplification. By utilizing polarization isolation of the bi-directional CFBG, a swept laser centered at 1305 nm, with repetition rate of 10.3 MHz, optical power of 84 mW, and 3 dB bandwidth of 109 nm, is demonstrated. Ultrahigh speed 3D optical coherence tomography (OCT) structural imaging of a human palm in vivo using this swept laser is also demonstrated. We believe that this ultrahigh speed swept laser will greatly promote the OCT technique for industrial and biomedical applications.