Ultrafast and Highly Specific Detection of One-Base Mutated Cell-Free DNA at a Very Low Abundance.

Liquid biopsy as well as genotyping plays important roles in guiding the use of tumor-targeted drugs and monitoring the generation of drug resistance. However, current methods, such as next-generation sequencing (NGS) and pyrosequencing, require long analysis time and complicated steps. To achieve ultrafast and highly specific detection of cell-free DNA (cfDNA) from blood, we improved our recently developed FEN1-aided RPA (FARPA), which combined flap endonuclease 1 (FEN1)-catalyzed invasive reactions with recombinase polymerase amplification (RPA) by inactivating the RPA enzymes before invasive reactions, designing short RPA primers, and changing invasive reaction conditions. Using the L858R and T790M mutations as examples, FARPA was sensitive to detect 5 copies of targeted mutants, specific to sense the mutants with an abundance as low as 0.01% from blood, and ultrafast to get results within 40 min. The method was readily expended to genotyping, and 15 min was enough to report the allele species directly from oral swab samples by coupling quick DNA extraction reagents. Validation was carried out by detecting clinical samples, including 20 cfDNA from patients with non-small cell lung cancer (NSCLC) for liquid biopsy and 43 human genomic DNA (gDNA) purified from blood (33) or lysed from oral swabs (10) for genotyping, giving 100% agreement with NGS and pyrosequencing, respectively. Furthermore, a portable battery-driven device with dual-channel fluorescence detection was successfully constructed to facilitate point-of-care testing (POCT) of liquid biopsy and genotyping, providing doctors with a potential tool to achieve genotyping- or mutant-guided personalized medicine at emergency or source-limited regions.

Obesity is associated with acute kidney injury in ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention: A national representative cohort study.

BACKGROUND: Acute kidney injury (AKI) is a frequent and potentially life-threatening complication after percutaneous coronary intervention (PCI) in patients with ST-segment-elevation myocardial infarction (STEMI). However, the relationship between obesity and the risk of AKI in this specific patient population has not been previously examined. METHODS: We queried the National Inpatient Sample (2016-2019) using ICD-10 codes to obtain a sample of adults with STEMI undergoing PCI. All patients were further subcategorized into obese and nonobese cohorts. The primary outcome was the incidence of AKI. Multivariate regression analysis was performed to assess the impact of obesity on AKI. The consistency of this correlation between subgroups was investigated using subgroup analysis and interaction testing. RESULTS: A total of 62,599 (weighted national estimate of 529,016) patients were identified, of which 9.80% (n = 6137) had AKI. Obesity comprised 19.78% (n = 1214) of the AKI cohort. Obese patients were on average younger, male, white, and had more comorbidities. Additionally, there was a significant positive association between obesity and AKI incidence (adjusted odds ratio [aOR]: 1.24, 95% confidence interval [CI]: 1.15-1.34), which was more pronounced in female patients (aOR: 1.56, 95% CI: 1.33-1.82, p < 0.001, p-interaction = 0.008). The AKI incidence in these patients increased steadily during the 4-year study period, and it was consistently higher in obese patients than in nonobese patients (p-trend < 0.001 for all). CONCLUSIONS: Obesity was independently associated with a greater risk of AKI among adults with STEMI undergoing PCI, particularly in female patients.

Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2).

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) is largely underdiagnosed and undertreated in China where few patients achieved recommended target levels of low density lipoprotein cholesterol (LDL-C). We conducted the first randomized, placebo-controlled clinical trial in Chinese patients with HeFH to assess the efficacy and safety of tafolecimab, a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody. METHODS: Patients diagnosed with HeFH by Simon Broome criteria and on a stable lipid-lowering therapy for at least 4 weeks were randomized 2:2:1:1 to receive subcutaneous tafolecimab 150 mg every 2 weeks (Q2W), tafolecimab 450 mg every 4 weeks (Q4W), placebo Q2W or placebo Q4W in the 12-week double-blind treatment period. After that, participants received open-label tafolecimab 150 mg Q2W or 450 mg Q4W for 12 weeks. The primary endpoint was the percent change from baseline to week 12 in LDL-C levels. Secondary endpoints included proportion of participants achieving ≥50% LDL-C reductions and proportion of participants with LDL-C <1.8 mmol/L at week 12 and 24, the change from baseline to week 12 in non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and lipoprotein(a) levels, as well as the change from baseline to week 24 in lipid levels. RESULTS: In total, 149 participants were randomized and 148 received at least one dose of the study treatment. At week 12, tafolecimab treatment induced significant reductions in LDL-C levels (treatment difference versus placebo [on-treatment estimand]: -57.4% [97.5% CI, -69.2 to -45.5] for 150 mg Q2W; -61.9% [-73.4 to -50.4] for 450 mg Q4W; both P <0.0001). At both dose regimens, significantly more participants treated with tafolecimab achieved ≥50% LDL-C reductions or LDL-C <1.8 mmol/L at week 12 as compared with corresponding placebo groups (all P <0.0001). Meanwhile, non-HDL-C, apolipoprotein B and lipoprotein(a) levels were significantly reduced in the tafolecimab groups at week 12. The lipid-lowering effects of tafolecimab were maintained till week 24. During the double-blind treatment period, the most commonly-reported adverse events in the tafolecimab groups included upper respiratory tract infection, increased blood creatine phosphokinase, increased alanine aminotransferase, increased aspartate aminotransferase and hypertension. CONCLUSIONS: Tafolecimab administered either 150 mg Q2W or 450 mg Q4W yielded significant and persistent reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with HeFH. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04179669.

Functional interplay of histone lysine 2-hydroxyisobutyrylation and acetylation in Arabidopsis under dark-induced starvation.

Lysine 2-hydroxyisobutyrylation (Khib) is a novel type of histone acylation whose prevalence and function in plants remain unclear. Here, we identified 41 Khib sites on histones in Arabidopsis thaliana, which did not overlap with frequently modified N-tail lysines (e.g. H3K4, H3K9 and H4K8). Chromatin immunoprecipitation-sequencing (ChIP-seq) assays revealed histone Khib in 35% of protein-coding genes. Most Khib peaks were located in genic regions, and they were highly enriched at the transcription start sites. Histone Khib is highly correlated with acetylation (ac), particularly H3K23ac, which it largely resembles in its genomic and genic distribution. Notably, co-enrichment of histone Khib and H3K23ac correlates with high gene expression levels. Metabolic profiling, transcriptome analyses, and ChIP-qPCR revealed that histone Khib and H3K23ac are co-enriched on genes involved in starch and sucrose metabolism, pentose and glucuronate interconversions, and phenylpropanoid biosynthesis, and help fine-tune plant response to dark-induced starvation. These findings suggest that Khib and H3K23ac may act in concert to promote high levels of gene transcription and regulate cellular metabolism to facilitate plant adaption to stress. Finally, HDA6 and HDA9 are involved in removing histone Khib. Our findings reveal Khib as a conserved yet unique plant histone mark acting with lysine acetylation in transcription-associated epigenomic processes.

Separation and Qualitative Study of Mentha asiatica Boriss. Essential Oil Components by prep-GC, GC-QTOF-MS, NMR and Prediction of Bioactive Compounds.

In order to understand the material basis of wild Mentha asiatica Boris. in Xinjiang, the chemical constituents of essential oil extracted from aerial parts of this plant were studied. A total 52 components were detected and 45 compounds were identified. First of all, the essential oil was separated by silica gel column chromatography, and divided into several parts according to the results of thin layer chromatography. Eight fractions were obtained, and then each fragment was preliminarily screened for antibacterial activity. It was found that all eight fragments had certain antibacterial activity in different level. Then the fractions were subjected to preparative gas chromatography (prep-GC) for further isolation. Ten compounds were identified by 13 C-NMR, 1 H-NMR and gas chromatography-quadrupole time of flight-Mass spectrometry (GC-QTOF-MS). They are sabinene, limonene and ß-caryophyllene, (1R*,3S*,5R*)-sabinyl acetate, piperitone oxide, rotundifolone, thymol, piperitone, 4-hydroxypiperiditone, cedrol. After screened by bioautography, 4-hydroxypiperone and thymol were showed best antibacterial activity. The inhibitory effects of the two isolated compounds on Candida albicans and their related mechanisms were studied. The results showed that, 4-hydroxypiperone and thymol significantly reduced ergosterol content on the surface of Candida albicans cell membrane in a dose-dependent manner. This work has accumulated experience for the development and utilization of Xinjiang characteristic medicinal plant resources and new drug research and development, and provided scientific basis and support for the later research and development of Mentha asiatica Boris.

Digital Nucleic Acid Signal Amplification Platform for Highly Sensitive DNA Mutation Analysis.

Digital nucleic acid analysis technology has shown great application potential due to its excellent performance. However, most current digital nucleic acid detection methods are based on PCR or other template amplification strategies. Here, we present an alternative analysis platform based on digital nucleic acid signal amplification in droplets termed dNASA. Using a bead-based controllable extension bridged cascade signal amplification reaction, we achieved an ultralow background, high efficiency, and highly specific nucleic acid signal amplification analysis. As a "proof of concept", we demonstrated the feasibility of the proposed dNASA platform in single-base DNA mutation analysis using artificially synthesized samples. This platform provides innovative ideas for the field of digital nucleic acid analysis.

Flap Endonuclease-Induced Steric Hindrance Change Enables the Construction of Multiplex and Versatile Lateral Flow Strips for DNA Detection.

A lateral flow strip (LFS) is an ideal tool for point-of-care testing (POCT), but traditional LFSs cannot be used for multiplex detection. Herein, a multiplex and versatile LFS based on flap endonuclease 1 (FEN1)-induced steric hindrance change (FISH-LFS) is proposed. In this method, multiplex PCR coupled with cascade invasive reactions was employed to yield single-stranded flaps, which were target-specific but independent of target sequences. Then, the amplicons were applied for FISH-LFS, and the single-stranded flaps would be efficiently captured by the complementary LFS-probes at different test lines. As flaps were cleaved from the specially designed hairpin probes, competition among flaps and hairpin probes would occur in capturing the probes at test lines. We enabled the hairpin probes to flow through the test lines while the flaps to stay at the test lines by making use of the difference in steric hindrance between hairpin probes and flaps. The assay is able to detect as low as two copies of blood pathogens (HBV, HCV, and HIV), to pick up as low as 0.1% mutants from wild-type gDNA, and to genotype 200 copies of SARS-CoV-2 variants α and ß within 75 min at a conventional PCR engine. As the method is free of dye, a portable PCR engine could be used for a cost-effective multiplex detection on site. Results using an ultrafast mobile PCR system for FISH-LFS showed that as fast as 30 min was achieved for detecting three pathogens (HBV, HCV, and HIV) in blood, very suitable for POCT of pathogen screening. The method is convenient in operation, simple in instrumentation, specific in genotyping, and very easy in setting up multiplex POCT assays.

Lipid membrane anchoring and highly specific fluorescence detection of cancer-derived exosomes based on postfunctionalized zirconium-metal-organic frameworks.

Cancer-derived exosomes carry a variety of important biomarkers specific to the formation, invasion and metastasis of tumor tissue. Dynamic monitoring of exosomes originated from cancer cells has clinical significance. Here we proposed a novel method to employ zirconium-metal-organic frameworks (Zr-MOFs) for extracting and identifying exosomes from blood. At first UiO-66 was magnetically modified as the adsorbent to anchor exosomes by forming Zr-O-P bonds. Then UiO-66-NH2 modified with anti-EpCAM was used to construct the fluorescent probe to recognize the extracted EpCAM-positive exosomes by forming a "MOF-exosome-MOF" structure. The proposed fluorescence detection method was evaluated by quantifying MCF-7 cell-derived exosomes at the concentration as low as 16.72 particles/µl. This method was successfully applied to analyze exosomes in the plasma samples from healthy donors and breast cancer patients, demonstrating that our method might have a great potential in assisting the early diagnosis and in dynamically monitoring the efficacy of cancer treatment. We believe that the method could be extended to the detection of other biomarkers in exosomes derived from cancer cell.

Flap Endonuclease 1-Assisted DNA Walkers for Sensitively and Specifically Sensing ctDNAs.

DNA walkers have shown superior performance in biosensing due to their programmability to design molecular walking behaviors with specific responses to different biological targets. However, it is still challenging to make DNA walkers capable of distinguishing DNA targets with single-base differences, so that DNA walkers that can be used for circulating tumor DNA sensing are rarely reported. Herein, a flap endonuclease 1 (FEN 1)-assisted DNA walker has been proposed to achieve mutant biosensing. The target DNA is captured on a gold nanoparticle (AuNP) as a walking strand to walk by hybridizing to the track strands on the surface of the AuNP. FEN 1 is employed to report the walking events by cleaving the track strands that must form a three-base overlapping structure recognized by FEN 1 after hybridizing with the captured target DNA. Owing to the high specificity of FEN 1 for structure recognition, the one-base mutant DNA target can be discriminated from wild-type DNA. By constructing a sensitivity-enhanced DNA walker system, as low as 1 fM DNA targets and 0.1% mutation abundance can be sensed, and the theoretical detection limits for detecting the DNA target and mutation abundance achieve 0.22 fM and 0.01%, respectively. The results of epidermal growth factor receptor (EGFR) L858R mutation detection on cell-free DNA samples from 15 patients with nonsmall cell lung cancer were completely consistent with that of next-generation sequencing, indicating that our DNA walker has potential for liquid biopsy.

Direct economic burden of patients with tuberculous meningitis in western China.

OBJECTIVE: To estimate the direct economic burden of tuberculous meningitis (TBM) in China for the first time. METHODS: Patients who were first diagnosed with TBM from December 2015 to December 2018 in Western China Hospital were enrolled. We retrospectively collected data on demographic and clinical features, resource utilization, costs, and long-term outcomes. The patients were followed up for 15-53 months. We performed a cost-of-illness study and analyzed the cost contributors with a generalized linear model. RESULTS: In total, the cases of 154 TBM patients (95 males, 59 females, aged 14-82 years) were reviewed. The average total direct cost per person was USD (United States dollars) 9,484 (range 1,822-67,285), with a mean direct medical cost of USD 8,901 (range 1,189-67,049). The average inpatient cost and drug cost after discharge were USD 6,837 (range 845-52,921) and USD 1,967 (range 0-60,423), respectively. The mean direct nonmedical cost was USD 583 (range 33-3,817), which accounted for 6.2% of the total direct cost. The average length of stay (LOS) in hospital was 25.0 days (range 6-152). A total of 117 of the patients (76.0%) had good outcomes (mRS = 0-2). There was no significant difference in the costs, LOS, or outcomes between rural and urban patients. Contributors to total direct cost were definite TBM, fever, coma, seizures, multidrug resistance, hydrocephalus, and poor long-term outcome. CONCLUSIONS: Although the accessibility of medical resources in remote and rural regions has significantly improved in China, the cost of TBM imposes a catastrophic burden on patients.

Point-of-care DNA testing by automatically and sequentially performing extraction, amplification and identification in a closed-type cassette.

Nucleic acid detection is important for clinical diagnostics; however, it is challenging to perform genetic testing at the point-of-care due to the tedious steps involved in DNA extraction and the risk of cross-contamination from amplicons. To achieve a fully-automated and contamination-free nucleic acid detection, we propose a closed-type cassette system which enables the following steps to be operated automatically and sequentially: sample preparation based on magnetic beads, target amplification using multiplex polymerase chain reaction, and colorimetric detection of amplicons using a serial invasive reaction coupled with the aggregation of gold nanoparticle probes. The cassette was designed to be round and closed, and 10 targets in a sample could be simultaneously detected by the naked eye or using a spectrophotometer in the system. In addition, a cassette-driven device was fabricated to transfer reagents between wells, to control the temperature of each reaction, and to sense the colour in the detection wells. The cassette system was sensitive enough to detect 10 genotypes at 5 single nucleotide polymorphism sites related to the anticoagulant's usage, by using a 0.5 µL blood sample. The accuracy of the system was evaluated by detecting 12 whole blood samples, and the results obtained were consistent with those obtained using pyrosequencing. The cassette is airtight and the whole system is fully automatic; the only manual operation is the addition of the sample to the cassette, performing point-of-care genetic testing in a sample-in/answer-out way.

A small non-coding RNA facilitates Brucella melitensis intracellular survival by regulating the expression of virulence factor.

Brucella species are the causative agents of brucellosis, a worldwide zoonotic disease that affects a broad range of mammals and causes great economic losses. Small regulatory RNAs (sRNAs) are post-transcriptional regulatory molecules that participate in the stress adaptation and pathogenesis of Brucella. In this study, we characterized the role of a novel sRNA, BSR1141, in the intracellular survival and virulence of Brucella melitensis. The results show that BSR1141 was highly induced during host infections and under in vitro stress situations that simulated the conditions encountered within host phagocytes. In addition, a BSR1141 mutant showed reduced survival both under in vitro stress conditions and in mice, confirming the role of BSR1141 in Brucella intracellular survival. Bioinformatic and experimental approaches revealed that BSR1141 affects the expression of many target genes, including the Brucella virulence component virB2. These data indicate that BSR1141 could influence the expression of virB2, which is important for B. melitensis pathogenesis and intracellular survival. This work provides new insight into the mechanism of adaptation to environmental stress and into the pathogenesis of intracellular pathogens.

Cirsimaritin inhibits influenza A virus replication by downregulating the NF-κB signal transduction pathway.

BACKGROUND: Artemisia scoparia Waldst and Kit is a famous traditional Chinese medicine widely distributed in Xinjiang, China. Flavonoids extracted from it exhibits inhibitory activities against several influenza virus strains. Despite this fact, the antiviral properties of CST, one of such flavonoids, against the influenza virus has not been reported. Thus, the aim of this study is to investigate the anti-influenza virus efficacy and antiviral mechanism of CST. METHODS: The inhibitory activity of CST against influenza viruses was assessed by using viral titers and performing Western blot, qRT-PCR, and immunofluorescence assays in Madin-Darby canine kidney (MDCK) cells and a human monocytic cell line (THP-1). The mechanism of CST against influenza virus was analyzed by hemagglutination inhibition (HI) assay, neuraminidase (NA) inhibition assay, and Western blot. RESULTS: CST reduced viral titers and influenza A virus (IAV) RNA and protein synthesis in a dose-dependent manner. Mechanistically, CST had no inhibitory effect on the attachment and release processes of the viral life cycle, as indicated by the HI and NA assays. Conversely, the CST-mediated inhibition of IAV is possibly linked to the inactivation of the NF-κB/p65 signal pathway. CST also suppressed the activation of JNK MAPK and P38 MAPK in vitro. In line with NF-κB/p65 inhibition, the expression levels of proinflammatory cytokines (TNF-α, IL-1ß, IL-8, and IL-10) and the inflammation-related protein COX-2 were downregulated by CST. CONCLUSIONS: CST inhibited IAV replication by downregulating the NF-κB signal transduction pathway. CST may be a potential agent or supplement against IAV infection.

Correlations Between mRNA Levels of Centrosomal Protein 55 (CEP55) and Clinical Features of Patients with Lung Cancer.

BACKGROUND The aim of this study was to investigate the prognostic relevance of CEP55 in lung cancer (LC). MATERIAL AND METHODS LC microarray profile GSE30219 was obtained from the GEO database. The 2-sample t test was performed to clarify the difference in CEP55 expression between LC and normal lung tissue. The chi-square test and logistic regression analysis were preformed to investigate the relationship between CEP55 expression and the clinical features of LC patients. Log-rank test and Cox proportional hazards regression analysis were conducted to evaluate the disease-free survival (DFS) and overall survival (OS) of LC patients. Gene set enrichment analysis was conducted to investigate the related mechanisms. RESULTS CEP55 was significantly increased in LC cells relative to normal lung tissues (P<0.0001). Univariate and multivariate correlation analyses demonstrated that CEP55 expression was associated with advanced T and N staging of LC (P<0.0001). Survival analyses indicated that CEP55 expression was an independent risk factor for DFS (HR: 1.515, 95% CI: 1.277-1.797, P<0.0001) and OS (HR: 1.436, 95% CI: 1.278-1.615). CEP55 might affect the proliferation of LC cells through Myc signaling, DNA repair, and G2M checkpoint. CONCLUSIONS Our results indicated that CEP55 was increased in LC cells and was associated with poor clinical outcomes of LC patients, and could be a prognostic biomarker for LC.

Closed-Tube PCR with Nested Serial Invasion Probe Visualization Using Gold Nanoparticles.

BACKGROUND: Detecting DNA biomarkers related to personalized medicine could improve the outcome of drug therapy. However, personalized medicine in a resource-restrained hospital is very difficult because DNA biomarker detection should be performed by well-trained staff and requires expensive laboratory facilities. METHODS: We developed a gold nanoparticle-based "Tube-Lab" to enable DNA analysis in a closed tube. Gold nanoparticle-modified probes (GNPs) were used to construct an inexpensive and simple DNA sensor for signal readout. The method consists of 3 steps (template amplification, sequence identification, and GNP-based signal readout), bridged by an invasive reaction. With temperature control at each step, the 3 reactions proceed sequentially and automatically in a closed tube without any liquid transfer. We used Tube-Lab to detect different biomarkers in blood, tissue, and plasma, including US Food and Drug Administration-approved pharmacogenomic biomarkers (single nucleotide polymorphisms, somatic mutations). RESULTS: The combination of PCR-based template replication and invader-based signal amplification allowed detection of approximately 6 copies of input DNA and the selective pick up 0.1% mutants from large amounts of background DNA. This method highly discriminated polymorphisms and somatic mutations from clinical samples and allowed a "liquid biopsy" assay with the naked eye. CONCLUSIONS: Tube-Lab provides a promising and cost-effective approach for DNA biomarker analysis, including polymorphisms and somatic mutations from blood DNA, tissue DNA, or circulating tumor DNA in plasma, which are critical for personalized medicine.

The effect of biofeedback on nonneurological dysfunctional voiding in children: A meta-analysis and systematic review.

OBJECTIVE: This study was conducted to investigate the effect of biofeedback (BF) on the rehabilitation of children with nonneurological dysfunctional voiding (NDV). METHODS: RCTs were retrieved from various databases (published from inception to February 29, 2024). The effects of the BF and non-BF treatments were compared. A random-effects model was used to evaluate the combined data. RESULTS: Meta-analysis revealed that BF increased the maximum urinary flow rate (SMD = 3.78, 95% CI 1.33∼6.22), improved urination time (SMD = 5.88, 95% CI 3.75∼8.01), and reduced the postvoid residual (SMD = -19.18, 95% CI -27.03∼-11.33) and urinary tract infection incidence (RR = 0.43, 95% CI 0.21∼0.87). Electromyogram activity (RR = 0.46, 95% CI 0.25∼0.84) and abnormal urination patterns (RR = 0.51, 95% CI 0.35∼0.74) improved, with effects persisting for more than 1 year. However, the effect of BF on the mean urinary flow rate in children with NDV was significant only after 1 year of follow-up (SMD = 1.90, 95% CI 0.87∼2.92). CONCLUSION: Existing evidence indicates that BF can enhance urinary parameters and patterns in children with NDV. However, its effectiveness in addressing constipation, daytime urinary incontinence, and nocturnal urinary incontinence is not substantial. High-quality randomized controlled trials can offer additional insights.

The prevalence of hepatitis B virus infection among HIV-infected patients in the Ningxia Hui Autonomous Region, China, November 2002 to July 2023.

We tested HIV-infected people with HBV serological markers of Ningxia. Of 1008 HIV-positive individuals, 70 (6.9 %) tested positive for HBsAg, 570 (56.5 %) tested positive for anti-HBs, and 483 (47.9 %) tested positive for anti-HBc. Of 70 HBV-positive individuals, 13 (18.5 %) tested positive for HBeAg, 31 (44.3 %) tested positive for anti-HBe, 3 (4.2 %) exhibited acute infection.

Primary exophytic urothelial carcinoma of the bladder: A case report.

RATIONALE: Bladder urothelial carcinoma (UC) is a common urinary system tumor that is generally diagnosed by cystoscopy combined with pathological biopsy. However, complete exophytic UC of the bladder is very rare and difficult to diagnose. Early diagnosis and accurate identification of such tumors, followed by aggressive surgical treatment, is essential for the management of these patients. PATIENT CONCERNS: An 84-year-old man was admitted to the hospital with dysuria, a poor diet, and significant weight loss. DIAGNOSIS: Pelvic computed tomography and magnetic resonance imaging revealed an exteriophytic round mass on the right lateral wall of the bladder. Cystoscopy revealed a necrotic mass on the right lateral wall of the bladder cavity, and no tumor cells were found following the biopsy. The tumor was removed via partial cystectomy, and the pathological result indicated high-grade muscle-invasive UC. INTERVENTIONS: The patient refused radical cystectomy and underwent laparoscopic partial cystectomy plus pelvic lymph node dissection followed by cisplatin plus gemcitabine chemotherapy. OUTCOMES: The patient's mental state and appetite were significantly improved after the urinary tube was removed 1 week after surgery. His general state was significantly improved after 1 month of follow-up but died of acute cerebral infarction 3 months after surgery. LESSONS: UC of the bladder may grow completely out of the bladder without symptoms such as gross hematuria; thus, early diagnosis is difficult. For high-risk individuals, regular imaging tests may help to detect tumors early. Partial cystectomy is a reliable surgical modality for bladder preservation in such patients.

Comparative efficacy of various pharmacologic treatments for alcohol withdrawal syndrome: a systematic review and network meta-analysis.

This study was to compare multiple classes of medications and medication combinations to find alternatives or additives for patients not applicable to benzodiazepines (BZDs). We performed a network meta-analysis to assess the comparative effect of 11 pharmacologic treatments in patients with alcohol withdrawal syndrome. Forty-one studies were included, comprising a total sample size of 4187 participants. The pooled results from the randomized controlled trials showed that there was no significant difference in the Clinical Institute Withdrawal Assessment-Alcohol, revised (CIWA-Ar) reduction with other medications or medication combinations compared to BZDs. Compared to BZDs, the mean difference in ICU length of stay of anticonvulsants + BZDs was -1.71 days (95% CI = -2.82, -0.59). Efficacy rankings from cohort studies showed that anticonvulsant + BZDs were superior to other treatments in reducing CIWA-Ar scores and reducing the length of stay in the ICU. Synthesis results from randomized controlled trials indicate that there are currently no data suggesting that other medications or medication combinations can fully replace BZDs. However, synthetic results from observational studies have shown that BZDs are effective in the context of adjuvant anticonvulsant therapy, particularly with early use of gabapentin in combination with BZDs in the treatment of alcohol withdrawal syndrome, which represents a promising treatment option.

Profiling the volatile compounds of Peganum harmala L. Based on multiple sample preparation coupled with gas chromatography-mass spectrometry analysis and explored its antidepressants-like activity.

Peganum harmala L., a traditional medicinal plant in China, is renowned for its significant alkaloid content in seeds and roots exhibiting a wide range of pharmacological activities, including antidepressant, antiseptic, and antiviral. However, the volatile composition of the herb remained unclear. Apart from that, the extraction of volatile compounds through essential oil presents challenges due to the low yield and the degradation of volatile active compounds at high temperatures. This study used multiple sample preparation methods including headspace (HS), needle trap device (NTD), and liquid-liquid extraction (LLE) coupled with gas chromatography-mass spectrometry (GC-MS) to analyze the volatile compounds from the areal part of P. harmala L.. A total of 93 compounds were identified with NTD facilitating the first detection of harmine among the volatile organic compounds. Through network pharmacology and protein interaction analysis, the compounds' potential therapeutic targets of the compounds were explored, and 23 key targets were obtained (AKT1, ALB, PTGS2, MAOA, etc). KEGG pathway enrichment analysis indicated significant involvement in neuroactive ligand-receptor interactions and serotonergic synapses. The results enhanced the understanding of P. harmala's pharmacological mechanisms and supported its ethnopharmacological use.