Deficiency of SDHC promotes metastasis by reprogramming fatty acid metabolism in colorectal cancer.

BACKGROUND: Several studies have demonstrated a strong correlation between impaired Succinate dehydrogenase (SDH) function and the advancement of tumors. As a subunit of SDH, succinate dehydrogenase complex subunit C (SDHC) has been revealed to play tumor suppressive roles in several cancers, while its specific role in colorectal cancer (CRC) still needs further investigation. METHODS: Online database were utilized to investigate the expression of SDHC in colorectal cancer and to assess its correlation with patient prognosis. Cell metastasis was assessed using transwell and wound healing assays, while tumor metastasis was studied in a nude mice model in vivo. Drug screening and RNA sequencing were carried out to reveal the tumor suppressor mechanism of SDHC. Triglycerides, neutral lipids and fatty acid oxidation were measured using the Triglyceride Assay Kit, BODIPY 493/503 and Colorimetric Fatty Acid Oxidation Rate Assay Kit, respectively. The expression levels of enzymes involved in fatty acid metabolism and the PI3K/AKT signaling pathway were determined by quantitative real-time PCR and western blot. RESULTS: Downregulation of SDHC was found to be closely associated with a poor prognosis in CRC. SDHC knockdown promoted CRC metastasis both in vitro and in vivo. Through drug screening and Gene set enrichment analysis, it was discovered that SDHC downregulation was positively associated with the fatty acid metabolism pathways significantly. The effects of SDHC silencing on metastasis were reversed when fatty acid synthesis was blocked. Subsequent experiments revealed that SDHC silencing activated the PI3K/AKT signaling axis, leading to lipid accumulation by upregulating the expression of aldehyde dehydrogenase 3 family member A2 (ALDH3A2) and reduction of fatty acid oxidation rate by suppressing the expression of acyl-coenzyme A oxidase 1 (ACOX1) and carnitine palmitoyltransferase 1A (CPT1A). CONCLUSIONS: SDHC deficiency could potentially enhance CRC metastasis by modulating the PI3K/AKT pathways and reprogramming lipid metabolism.

Seeking the adsorption of tetracycline in water by Fe-modified sludge biochar at different pyrolysis temperatures.

The composite material SBC-Fe-x with sludge and Fe3+ was developed by different calcination temperatures (600, 700, and 800 °C) for the removal of tetracycline (TC). The adsorption rates of SBC-Fe-600, SBC-Fe-700, and SBC-Fe-800 were 77.5%, 89%, and 91%, respectively. Furthermore, the Langmuir model indicated that the maximum adsorption capacity of SBC-Fe-700 (157.93 mg/g) was three times greater than that of SBC-Fe-600. The conclusions were confirmed by a series of characterizations that SBC-Fe-700 showed a larger specific surface area, well-developed pore structure, rich oxygen-containing functional groups and a high degree of graphitization. The results of pH experiments indicated the broad applicability of SBC-Fe-700 for TC adsorption. In addition, SBC-Fe-700 suggested outstanding performance in different water environments. This work produced a feasible adsorbent for the removal of TC, and a new direction for sludge resource utilization was proposed.

Randomized clinical trial on D2 lymphadenectomy versus D2 lymphadenectomy plus complete mesogastric excision in patients undergoing gastrectomy for cancer (DCGC01 study).

BACKGROUND: It is unknown whether D2 lymphadenectomy + complete mesogastric excision for gastric cancer improves survival compared with just D2 lymphadenectomy. METHODS: Between September 2014 and June 2018, patients with advanced gastric cancer were randomly assigned (1 : 1) to laparoscopic D2 lymphadenectomy or D2 lymphadenectomy + complete mesogastric excision gastrectomy. The modified intention-to-treat population was defined as patients who had pathologically confirmed gastric adenocarcinoma (pT1 N1-3 M0 and pT2-4 N0-3 M0). The primary endpoint was 3-year disease-free survival. Secondary endpoints were the recurrence pattern and overall survival. RESULTS: The median follow-up of patients in the D2 lymphadenectomy group (169 patients) and patients in the D2 lymphadenectomy +complete mesogastric excision group (169 patients) was 55 (interquartile range 37-60) months and 51 (interquartile range 40-60) months respectively. Recurrence occurred in 50 patients in the D2 lymphadenectomy group (29.6%) versus 33 patients in the D2 lymphadenectomy + complete mesogastric excision group (19.5%) (P = 0.032). The 3-year disease-free survival was 75.5% (95% c.i. 68.3% to 81.3%) in the D2 lymphadenectomy group versus 85.0% (95% c.i. 78.7% to 89.6%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.042). The HR for recurrence in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 0.99) by Cox regression (P = 0.045). The 3-year overall survival rate was 77.5% (95% c.i. 70.4% to 83.1%) in the D2 lymphadenectomy group versus 85.8% (95% c.i. 79.6% to 90.2%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.058). The HR for death in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 1.02) (P = 0.058). CONCLUSION: Compared with conventional D2 dissection, D2 lymphadenectomy + complete mesogastric excision is associated with better disease-free survival, but there is no statistically significant difference in overall survival. REGISTRATION NUMBER: NCT01978444 (http://www.clinicaltrials.gov).

Draft Genome Sequence of Candida saopaulonensis from a Very Premature Infant with Sepsis.

The rare fungus Candida saopaulonensis has never been reported to be associated with human infection. We report the draft genome sequence of the first clinical isolate of C. saopaulonensis, which was isolated from a very premature infant with sepsis. This is the first genome assembly reaching the near-complete chromosomal level with structural annotation for this species, opening up avenues for exploring evolutionary patterns and genetic mechanisms of pathogenesis.

Broadband beam collimation metasurface for full-color micro-LED displays.

Near-eye displays are widely recognized as a groundbreaking technological advancement with the potential to significantly impact daily life. Within the realm of near-eye displays, micro-LEDs have emerged as a highly promising technology owing to their exceptional optical performance, compact form factor, and low power consumption. However, a notable challenge in integrating micro-LEDs into near-eye displays is the efficient light collimation across a wide spectrum range. In this paper, we propose what we believe to be a novel design of a broadband beam collimation metasurface for full-color micro-LEDs by harnessing wavefront phase modulation based on Huygens' principle. Our results demonstrate a substantial reduction in the full width at half maximum (FWHM) angles, achieving a reduction to 1/10, 1/10, and 1/20 for red, green, and blue micro-LEDs compared to those without the metasurface, which is the best collimation result as far as we know. The central light intensity increases by 24.60, 36.49, and 42.15 times. Furthermore, the significant enhancement in the light energy within ±10° is achieved, with the respective multiplication factors of 14.16, 15.60, and 13.00. This metasurface has the potential to revolutionize the field by enabling high-performance, compact, and lightweight micro-LED displays, with applications in near-eye displays, micro-projectors, and beyond.

More potential uses of specific perforator flaps in the calf - A cadaveric study on the subdermal vascular structure of the lower leg.

BACKGROUND: The perforator flap has garnered significant interest since its inception due to its advantage of not needing a vascular network at the deep fascial level. Perforator flaps are commonly utilized in different flap transplant surgeries, and the thigh flap is presently the most widely used perforator flap. Is it possible for the calf to replace the thigh as a more suitable site for harvesting materials? Currently, there is a lack of relevant anatomical research. This study aims to address this question from an anatomical and imaging perspective. METHODS: This study used cadavers to observe the branches and courses of perforators on the calf and the distribution of skin branches using microdissection techniques, digital X-ray photography, and micro-computed tomography techniques. RESULTS: The perforators had three main branches: the vertical cutaneous branch, the oblique cutaneous branch, and the superficial fascial branch. The superficial fascial branch traveled in the superficial fascia and connected with the nearby perforators. The vertical and oblique cutaneous branches entered the subdermal layer and connected with each other to create the subdermal vascular network. CONCLUSIONS: We observed an intact calf cutaneous branch chain between the cutaneous nerve and the perforator of the infrapopliteal main artery at the superficial vein site. Utilizing this anatomical structure, the calfskin branch has the potential to serve as a substitute for thigh skin flap transplantation and may be applied to perforator flap transplantation in more locations.

Metabolomics in cirrhosis: Recent advances and opportunities.

Liver cirrhosis (LC) represents a significant hepatic disorder that persistently commands the attention of the scientific community, especially concerning its pathogenesis and therapeutic approaches. Metabolomics, the comprehensive profiling of an organism's metabolome, has been increasingly applied in the research of cirrhosis over the past decade. This review summarizes the recent advancements and applications of metabolomics within the context of LC research, in recent five years. It highlights the role of metabolomics in the diagnosis of LC, the assessment of prognostic markers, and the evaluation of therapeutic outcomes. The discussion focuses on the potential and challenges of metabolomics in LC research, including the evolution of analytical technologies, advancements in bioinformatics, and the challenges impeding clinical implementation. Additionally, the review anticipates the forthcoming developments in metabolomics related to LC research, with the objective of facilitating innovative approaches for early detection and intervention in LC.

Constructing a Titanium Silicon Molecular Sieve-Based Z-Scheme Heterojunction with Enhanced Photocatalytic Activity.

Titanium silicon molecular sieve (TS-1) is an oxidation catalyst that possesses a long lifetime of charge transfer excited state, high Ti utilization efficiency, large specific surface area, and good adsorption property; therefore, TS-1 acts as a Ti-based photocatalyst candidate. In this work, TS-1 coupled Bi2MoO6 (TS-1/BMO) photocatalysts were fabricated via a facile hydrothermal route. Interestingly, the optimized TS-1/BMO-1.0 catalyst exhibited a decent photodegradation property toward tetracycline hydrochloride (85.49% in 120 min) under the irradiation of full spectrum light, which were 4.38 and 1.76 times compared to TS-1 and BMO, respectively. The enhanced photodegradation property of the TS-1/BMO-1.0 catalyst could be attributed to the reinforced light-harvesting capacity of the photocatalyst, high charge mobility, and suitable band structure for tetracycline hydrochloride degradation. In addition, the mechanism of photocatalytic degradation of tetracycline hydrochloride by the TS-1/BMO-1.0 catalyst was reasonably proposed based on the band structure, trapping, and ESR tests. This research provided feasible ideas for the design and construction of high-efficiency photocatalysts for contaminant degradation.

Epstein-Barr virus suppresses N6-methyladenosine modification of TLR9 to promote immune evasion.

Epstein-Barr virus (EBV) is a human tumor virus associated with a variety of malignancies, including nasopharyngeal carcinoma, gastric cancers, and B-cell lymphomas. N6-methyladenosine (m6A) modifications modulate a wide range of cellular processes and participate in the regulation of virus-host cell interactions. Here, we discovered that EBV infection downregulates toll-like receptor 9 (TLR9) m6A modification levels and thus inhibits TLR9 expression. TLR9 has multiple m6A modification sites. Knockdown of METTL3, an m6A "writer", decreases TLR9 protein expression by inhibiting its mRNA stability. Mechanistically, Epstein-Barr nuclear antigen 1 increases METTL3 protein degradation via K48-linked ubiquitin-proteasome pathway. Additionally, YTHDF1 was identified as an m6A "reader" of TLR9, enhancing TLR9 expression by promoting mRNA translation in an m6A -dependent manner, which suggests that EBV inhibits TLR9 translation by "hijacking" host m6A modification mechanism. Using the METTL3 inhibitor STM2457 inhibits TLR9-induced B cell proliferation and immunoglobulin secretion, and opposes TLR9-induced immune responses to assist tumor cell immune escape. In clinical lymphoma samples, the expression of METTL3, YTHDF1, and TLR9 was highly correlated with immune cells infiltration. This study reveals a novel mechanism that EBV represses the important innate immunity molecule TLR9 through modulating the host m6A modification system.

Investigating the efficiency of a two-stage anaerobic-aerobic process for the treatment of confectionery industry wastewaters with simultaneous production of biohydrogen and polyhydroxyalkanoates.

The scope of the current study was to investigate the efficiency of a two-stage anaerobic-aerobic process for the simultaneous treatment and valorization of selective wastewater streams from a confectionary industry. The specific wastewater (confectionary industry wastewater, CIW) was a mixture of the rinsing eluting during washing of the cauldrons in which jellies and syrups were produced, and contained mainly readily fermentable sugars, being thus of high organic load. The first stage of the process was the dark fermentation (DF) of the CIW in continuous, attached-biomass systems, in which the effect on hydrogen yields and distribution of metabolites were studied for different packing materials (ceramic or plastic), hydraulic retention times, HRTs (12 h-30 h) and feed substrate concentration (20 g COD/L- 50 g COD/L). In the second stage, the effectiveness of the aerobic treatment of the DF effluents was evaluated in terms of the reduction of the organic load and the production of polyhydroxyalkanoates (PHAs) through an enriched mixed microbial culture (MMC). The MMC was developed in a continuous draw and fill system, in which the accumulation potential of PHAs was studied. It was shown that the hydrogen production rates decreased for increasing substrate concentration and HRTs, with a maximum of 12.70 ± 0.35 m3 H2/m3 initial CIW achieved for the lowest HRT and feed concentration and using ceramic beads as packing material. Butyrate, acetate and lactate were the main metabolites generated in all cases, in different ratios. The distribution of metabolites during DF was shown to highly affect the efficiency of the second process in terms of both the reduction of organic load and the PHAs yields. The highest removal of organic load achieved after 48 h of aerobic treatment was 84.0 ± 0.9 %, whereas the maximum PHAs yield was 21.46 ± 0.13 kg PHAs/m3 initial CIW.

Camrelizumab and apatinib plus induction chemotherapy and concurrent chemoradiotherapy in stage N3 nasopharyngeal carcinoma: a phase 2 clinical trial.

The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of immunotherapy to standard treatment could improve efficacy is unclear. In this phase II clinical trial (ChiCTR2000032317), 49 patients with stage TanyN3M0 nasopharyngeal carcinoma were enrolled and received the combination of three cycles of induction chemotherapy, camrelizumab and apatinib followed by chemoradiotherapy. Here we report on the primary outcome of distant metastasis-free survival and secondary end points of objective response rate, failure-free survival, locoregional recurrence-free survival, overall survival and toxicity profile. After induction therapy, all patients had objective response, including 13 patients (26.5%) with complete response. After a median follow-up of 28.7 months, the primary endpoint of 1-year distant metastasis-free survival was met for the cohort (1-year DMFS rate: 98%). Grade≥3 toxicity appeared in 32 (65.3%) patients, with the most common being mucositis (14[28.6%]) and nausea/vomiting (9[18.4%]). In this work, camrelizumab and apatinib in combination with induction chemotherapy show promising distant metastasis control with acceptable safety profile in patients with stage TanyN3M0 nasopharyngeal carcinoma.

Simultaneous ammonia and nitrate removal by novel integrated partial denitrification-anaerobic ammonium oxidation-bioelectrochemical system.

The current study explored the performance of an integrated partial denitrification-anaerobic ammonium oxidation (anammox)-bioelectrochemical system on simultaneous removal of ammonia nitrogen and nitrate nitrogen. Different operational conditions were selected to optimize critical parameters of the process for improving nitrogen removal. The results indicated that more than 90 % of total inorganic nitrogen removal efficiency was achieved under the optimal conditions: ammonia nitrogen/nitrate nitrogen ratio of 1:2, external resistance of 200 Ω and inoculation volume ratio of anammox bacteria/denitrifying at 2:1. Improved nitrogen removal under the optimal conditions were confirmed by microbial community changes (Candidatus Brocadia and Thiobacillus) and enhanced of nitrogen metabolism-related genes (hao, hzsA/C and hdh). Increases of Limnobacter indicated an enhanced electron transfer efficiency. Overall, high-efficiency and stable nitrogen removal efficiency without nitrite nitrogen accumulation could be achieved by the integrated system under the optimal conditions, providing novel insights for simultaneous treatment of domestic wastewater and groundwater.

Functional outcomes of different surgical treatments for common peroneal nerve injuries: a retrospective comparative study.

BACKGROUND: This study aims to assess the recovery patterns and factors influencing outcomes in patients with common peroneal nerve (CPN) injury. METHODS: This retrospective study included 45 patients with CPN injuries treated between 2009 and 2019 in Jing'an District Central Hospital. The surgical interventions were categorized into three groups: neurolysis (group A; n = 34 patients), nerve repair (group B; n = 5 patients) and tendon transfer (group C; n = 6 patients). Preoperative and postoperative sensorimotor functions were evaluated using the British Medical Research Council grading system. The outcome of measures included the numeric rating scale, walking ability, numbness and satisfaction. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal time interval between injury and surgery for predicting postoperative foot dorsiflexion function, toe dorsiflexion function, and sensory function. RESULTS: Surgical interventions led to improvements in foot dorsiflexion strength in all patient groups, enabling most to regain independent walking ability. Group A (underwent neurolysis) had significant sensory function restoration (P < 0.001), and three patients in Group B (underwent nerve repair) had sensory improvements. ROC analysis revealed that the optimal time interval for achieving M3 foot dorsiflexion recovery was 9.5 months, with an area under the curve (AUC) of 0.871 (95% CI = 0.661-1.000, P = 0.040). For M4 foot dorsiflexion recovery, the optimal cut-off was 5.5 months, with an AUC of 0.785 (95% CI = 0.575-0.995, P = 0.020). When using M3 toe dorsiflexion recovery or S4 sensory function recovery as the gold standard, the optimal cut-off remained at 5.5 months, with AUCs of 0.768 (95% CI = 0.582-0.953, P = 0.025) and 0.853 (95% CI = 0.693-1.000, P = 0.001), respectively. CONCLUSIONS: Our study highlights the importance of early surgical intervention in CPN injury recovery, with optimal outcomes achieved when surgery is performed within 5.5 to 9.5 months post-injury. These findings provide guidance for clinicians in tailoring treatment plans to the specific characteristics and requirements of CPN injury patients.

HDAC6 inhibitor ACY-1215 enhances STAT1 acetylation to block PD-L1 for colorectal cancer immunotherapy.

The search for effective combination therapy with immune checkpoint inhibitors (ICI) has become important for cancer patients who do not respond to the ICI well. Histone deacetylases (HDACs) inhibitors have attracted wide attention as anti-tumor agents. ACY-1215 is a selective inhibitor of HDAC6, which can inhibit the growth of a variety of tumor. We previously revealed that HDAC family is highly expressed in colorectal cancer specimens and mouse models. In this study, ACY-1215 was combined with anti-PD1 to treat tumor-bearing mice associated with colorectal cancer. ACY-1215 combined with anti-PD1 effectively inhibited the colorectal tumor growth. The expression of PD-L1 in tumor of mice were inhibited by ACY-1215 and anti-PD1 combination treatment, whereas some biomarkers reflecting T cell activation were upregulated. In a co-culture system of T cells and tumor cells, ACY-1215 helped T cells to kill tumor cells. Mechanically, HDAC6 enhanced the acetylation of STAT1 and inhibited the phosphorylation of STAT1, thus preventing STAT1 from entering the nucleus to activate PD-L1 transcription. This study reveals a novel regulatory mechanism of HDAC6 on non-histone substrates, especially on protein acetylation. HDAC6 inhibitors may be of great significance in tumor immunotherapy and related combination strategies.

Housing of electrosynthetic biofilms using a roll-up carbon veil electrode increases CO2 conversion and faradaic efficiency in microbial electrosynthesis cells.

Electrode-driven microbial electron transfer enables the conversion of CO2 into multi-carbon compounds. The electrosynthetic biofilms grow slowly on the surface and are highly susceptible to operational influences, such as hydrodynamic shear stress. In this study, a cylindrical roll-up carbon felt electrode was developed as a novel strategy to protect biofilms from shear stress within the reactor. The fabricated electrode allowed hydrogen bubble formation inside the structure, which enabled microbes to uptake hydrogen and convert CO2 to multi-carbon organic compounds. The roll-up electrode exhibited faster start-up and biofilm formation than the conventional linear shape carbon felt. The acetate yield and cathodic faradaic efficiency increased by 80% and 34%, respectively, and the bioelectrochemical stability was improved significantly. The roll-up structure increased biofilm development per unit electrode surface by three to five-fold. The roll-up configuration improved biofilm formation on the electrode, which enhanced the performance of microbial electrosynthesis-based CO2 valorization.

Prevalence of and risk factors for intestinal colonisation by multidrug-resistant Gram-negative bacteria in patients with haematological malignancies: A systematic review and meta-analysis.

BACKGROUND: Patients with haematological malignancies (HM patients) are at high risk of infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB). MDR-GNB intestinal colonisation is associated with MDR-GNB infections. The aim of this systematic review and meta-analysis on HM patients was to pool the prevalence of and risk factors for intestinal colonisation by MDR-GNB, including carbapenem-resistant Enterobacterales (CRE) and extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales, reported in previous studies. METHODS: This study was conducted according to the protocol registered in PROSPERO (CRD42022374425). PubMed, Embase, Web of Science, Ovid MEDLINE(R) ALL and Cochrane Library were searched from inception to 25 October 2022. Observational studies reporting CRE and/or ESBL intestinal colonisation in HM patients were included. Subgroup analyses were conducted by study region. RESULTS: A total of 21 402 HM patients from 32 studies were analysed. The pooled CRE and ESBL colonisation rates were 21.7% [95% confidence interval (95%CI) 18.7-24.8] and 19.2% (95%CI 13.9-24.5), respectively. Prior exposure to tigecycline [odds ratio (OR) 3.99, 95%CI 2.08-7.68], carbapenem (OR 1.84, 95%CI 1.13-2.97) or penicillin (OR 1.72, 95%CI 1.05-2.83), as well as chemotherapy (OR 2.45, 95%CI 1.05-5.73), neutropenia (OR 1.88, 95%CI 1.08-3.26) and acute myeloid leukaemia (AML; OR 1.86, 95%CI 1.33-2.61), were risk factors for CRE colonisation in HM patients. Prior antibiotic exposure was a risk factor for ESBL colonisation in HM patients (OR 4.90, 95%CI 2.76-8.70). CONCLUSIONS: This study shows the high prevalence of MDR-GNB (CRE and ESBL) colonisation in HM patients and explains associated factors for the colonisation. The results provide evidence for MDR-GNB infection control in HM management.

Revealing the "Yin-Jing" mystery veil of Platycodon grandiflorum by potentiating therapeutic effects and lung-oriented guidance property.

ETHNIC PHARMACOLOGICAL RELEVANCE: "Yin-Jing" medicine (YJM) has been widely used by both ancient and modern Chinese medicine practitioners during long-term clinical practice. However, it remains unclear how to best guide other medicines to the targeted organs in a traditional Chinese medicine (TCM) prescription. Here, in an attempt to explain the scientific connotation of the YJM property (YJMP) attributed to a basic TCM theory, Platycodon grandiflorum (PG) was chosen as a case study to reveal the mystery of YJMP theory. AIM OF THE STUDY: The main purpose of this study is to employ modern chemical and molecular biology methods to confirm the "Yin-Jing" effect of PG, and further clarify its material basis and related possible mechanism. MATERIALS AND METHODS: The ammonia-induced lung injury rat model was utilized to determine the optimal dosage of traditional prescription Hui Yan Zhu Yu decoction (HYZYD) using Wright Giemsa staining, HE staining, Masson staining, and TUNEL analysis. With the same way, PG was confirmed to have potentiating therapeutic effect (PTE) by comparison with HYZYD and [HYZYD-PG]. TMT proteomics was used to reveal the "Yin-Jing" mechanism of action. Western blot assay (WB) was employed for verification of differentially expressed proteins. Additionally, four non-crossing fragmentations (Fr. A-D) were characterized by RPLC/SEC-ELSD and HILIC-ESI--Q-OT-IT-MS techniques. The PTE and guidance property assays were utilized to evaluate "Yin-Jing" functions by a compatible combination of hydroxysafflor yellow A (HYA) using qPCR, FCM, WB, HPLC, high content cell imaging (HCI) and high-resolution live-cell imaging (HRLCI) techniques. RESULTS: The HYZYD-M (medium dose group) significantly improved the lung injury level in a pneumonia model of rats. PG enhanced the therapeutic effect of HYZYD ascribed to Yin-Jing PTE functions. TMT proteomics revealed a category of differentially expressed proteins ascribed to Golgi-ER between HYZYD and [HYZYD-PG]. Fr. C (i.e., saponins) and Fr. D (i.e., lipids) were determined as therapeutic fragmentations via the LPS-induced A549 cell injury model; however, Fr. B (fructooligosaccharides and small Mw fructans) had no therapeutic effect. Further compatibility PTE assays confirmed Fr. B significantly improved efficiency by a combination of HYA. The guidance assays showed Fr. B could significantly increase the uptake and distribution of HYA into lung cells and tissues. HCI assays showed that Fr. B increased uptake of HYA accompanied by significant activation of Golgi-ER. Unlike Fr. B, HRLCI showed that Fr. A, C and D were not only unobvious activations of Golgi-ER but also insignificant facilitation of colocalizations between HYA and Golgi-ER. CONCLUSIONS: Fr. B is believed to be a key YJMP material basis of PG attributed to Yin-Jing PTE with characteristic of lung-oriented guidance property, whereas another abound Fr. C was determined to have synergistic effects rather than Yin-Jing material basis.

Failure of intravenous nifekalant cardioversion as an independent predictor for persistent atrial fibrillation recurrence after catheter ablation.

AIMS: Nifekalant is a class III antiarrhythmic drug that exerts antiarrhythmic effects by inhibiting rapid rectifying potassium channels and extending the effective refractory period of cardiomyocytes. It has a high success rate in converting atrial fibrillation (AF) to sinus rhythm. Whether the failure of intravenous nifekalant cardioversion is an independent predictor for persistent AF recurrence after catheter ablation has not been reported. METHODS: A total of 92 patients with drug-refractory persistent AF were retrospectively enrolled. After all ablations, intravenous nifekalant was administrated. Patients were assigned to the success group (group 1) and failure group (group 2) based on nifekalant cardioversion results and followed for 12 months to note any episode of atrial arrhythmia recurrence. RESULTS: Each group included 46 patients. After 12 months of follow-up, nine (19.6%) patients from group 1 and 23 (50.0%) patients from group 2 had a recurrence of atrial tachyarrhythmia (P = 0.002). AF duration and type 2 diabetes were strongly associated with failure of intravenous nifekalant cardioversion. Univariable Cox proportional hazard regression showed that failure of intravenous nifekalant cardioversion, AF duration, and type 2 diabetes were potential risk factors. Multivariable Cox proportional hazard regression showed that failure of nifekalant cardioversion was statistically associated with AF recurrence (adjusted RR = 2.257, 95% CI: 1.006-5.066, P = 0.048). Failure of intravenous nifekalant cardioversion could bring a positive effect on the prognostic differentiation when added into the multivariable model (0.767 ± 0.042 vs. 0.774 ± 0.045, P = 0.025). CONCLUSION: Failure of nifekalant cardioversion is an independent predictor for persistent AF recurrence after catheter ablation.

Clinical Characteristics and Molecular Epidemiology of ST23 Klebsiella pneumoniae in China.

Purpose: In clinical settings, CG23 Klebsiella pneumoniae (Kp) is the most virulent clonal group of Kp. Continuous fusions of hypervirulent (Hv) and highly resistant strains have been reported; however, few studies have analysed the molecular epidemiology and clinical characteristics of CG23 strains, especially MDR-sequence type ST23 strains. In this study, we investigated the molecular characteristics of ST23 Kp and analysed the clinical characteristics of ST23 Kp infections in a large teaching hospital of the third class in China. Methods: ST23 Kp isolates were screened using whole-genome sequencing data from a large single centre. We compared the clinical characteristics of ST23 strains isolated from community-acquired infections (CAI) and hospital acquired infection (HAI). In addition, the infection characteristics of MDR and poor-prognosis isolates were investigated. We analysed genetic characteristics of ST23 Kp and further investigated the evolutionary relationship based on single-nucleotide polymorphism phylogenetic trees. Results: We detected 184 ST23 strains between 2013 and July of 2018. There were no significant differences between the isolation rates of pulmonary, bloodstream, urinary tract, and cutaneous soft tissue infections in the community and hospitals, except for abscess infections. MDR strains primarily cause pulmonary infections and abscesses; infections with a poor prognosis are typically bloodstream and pulmonary infections. Fourteen MDR strains producing extended-spectrum or class C beta-lactamases, resulting in resistance to third-generation cephalosporins. In 3.8% of ST23 Kp strains, the clb locus was absent. The phylogenetic tree revealed that the isolates were primarily divided into three clades, and based on clinical data, it is inferred that three clonal transmission events have occurred, mainly in ICU causing lung infection. Conclusion: This study demonstrates that virulence and drug-resistance fusion events of ST23 strains occur gradually, and that the hypervirulent clones facilitate the widespread dissemination of CAI and HAI, particularly pulmonary. Monitoring genomics and developing antivirulence strategies are essential.

Cadaveric feasibility study of modified contralateral C7 nerve transfer for targeted functional recovery in hemiplegic upper extremity.

BACKGROUND: Contralateral cervical seventh (cC7) nerve to C7 transfer has been proven effective for treating spastic upper limb. However, for those whose major impairment is not in the C7 area, cC7 nerve transfer to other nerve(s) may achieve a better outcome. The aim of this study was to explore the optimal surgical approach for transferring cC7 to one or two nerves by cadaveric study and to discuss the possible applications for hemiplegic patients. METHODS: Modified cC7 transfer to one (five procedures) or two nonadjacent (three procedures) nerve roots was proposed, and success rates of direct coaptation through two surgical approaches were compared: the superficial surface of longus colli (sLC) and the deep surface of longus colli (dLC) approaches. The length, diameter and distance of relevant nerves were also measured in 25 cadavers. RESULTS: Compared with the sLC approach, the distance of the dLC approach was 1.1 ± 0.3 cm shorter. The success rates for the sLC and dLC approaches were as follows, respectively: cC7-C5 surgery, 94% and reached 98%; cC7-C6 surgery, 54% and 96%; cC7-C7 surgery, 42% and 94%; cC7-C8 surgery, 34% and 94%; cC7-T1 surgery, 24% and 62%; cC7-C5C7 surgery, 74% and 98%; cC7-C6C8 surgery, 54% and 98%. cC7-C7T1 surgery, 42% and 88%. CONCLUSIONS: The dLC approach greatly improved direct coaptation rate for cC7 nerve transfer. The modified cC7 nerve transfer procedures are technically feasible for further application in clinic.