Intrathecal dexmedetomidine as an adjuvant to plain ropivacaine for spinal anesthesia during cesarean section: a prospective, double-blinded, randomized trial for ED50 determination using an up-down sequential allocation method.

BACKGROUND: Intrathecal dexmedetomidine, as an adjuvant to local anesthetics, has been reported to improve the quality of spinal anesthesia and reduce the required local anesthetic dose. However, the optimal dosage regimen for intrathecal dexmedetomidine combined with plain ropivacaine for cesarean section (CS) remains undetermined. The present study aimed to determine the median effective dose (ED50) of intrathecal dexmedetomidine as an adjuvant to plain ropivacaine for spinal anesthesia during CS. METHODS: Sixty parturients undergoing CS were randomly assigned to either group: plain ropivacaine 8 mg (Group Rop8) or plain ropivacaine 10 mg (Group Rop10). The initial dosage of intrathecal dexmedetomidine in each group was 5 µg. The effective dose was defined as a bilateral sensory block at the level of T6 or above to pinprick attained within 10 min after intrathecal injection, without the need for supplementary intraoperative epidural anesthesia. Effective or ineffective responses were determined, followed by a 1 µg increment or decrement in the dose of intrathecal dexmedetomidine for the next parturient using up-down sequential allocation. ED50 were calculated using probit regression. RESULTS: The ED50 of intrathecal dexmedetomidine with plain ropivacaine was 5.9 µg (95% confidence interval [CI], 4.9-7.4 µg) in Group Rop8 and 3.1 µg (95% CI, 0.1-4.8 µg) in Group Rop10 (P < 0.05). Hemodynamic stability, side effects, patient satisfaction and neonatal outcomes were comparable between the two groups. CONCLUSIONS: The present data suggested that the ED50 of intrathecal dexmedetomidine as an adjuvant to 8 mg and 10 mg plain ropivacaine in spinal anesthesia during cesarean section was approximately 6 µg and 3 µg, respectively. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2200055928.

Long non-coding RNA MCF2L-AS1 promotes the aggressiveness of colorectal cancer by sponging miR-874-3p and thereby up-regulating CCNE1.

BACKGROUND: Long non-coding RNAs (lncRNAs) have drawn growing attention because of the role which they play in various diseases, including colorectal cancer (CRC). However, the potential functions of lncRNA MCF2L antisense RNA 1 (MCF2L-AS1) in tumors remained largely unclear. The present study aimed to explore the clinical significance and the biological effects of lncRNA MCF2L antisense RNA 1 (MCF2L-AS1) in CRC. METHODS: Reverse transcriptase-polymerase chain reaction was performed to determine the expression of MCF2L-AS1 in CRC. The clinical significance of MCF2L-AS1 in CRC patients was analyzed statistically. In vitro experiments were performed to determine the effects of MCF2L-AS1 on the cellular progression of CRC cells. Bioinformatic assays, luciferase reporter assays and RNA-pulldown assays were performed to predict for potential microRNAs that can interact with MCF2L-AS1 and mRNAs that can interact with miR-874-3p. RESULTS: We identified a novel CRC-related lncRNA, MCF2L-AS1, which is distinctly highly expressed in CRC. Its diagnostic value for CRC patients was also demonstrated. Clinical assays revealed that high MCF2L-AS1 expression is associated with advanced stages, positive metastasis and the poor prognosis of CRC patients. Multivariate assays confirmed that MCF2L-AS1 expression is an independent poor prognostic factor for both 5-year overall survival and 5-year disease-free survival of CRC patients. Functionally, we confirmed that knockdown of MCF2L-AS1 distinctly suppresses the proliferation, migration and invasion of CRC cells and also promotes apoptosis. Mechanistic investigation showed that MCF2L-AS1 functions as an endogenous sponge for miR-874-3p to increase the expression of CCNE1. CONCLUSIONS: Our findings identified a novel CRC-related lncRNA, MCF2L-AS1, which may be used as a potential diagnostic and prognostic biomarker for CRC patients. In addition, the newly identified MCF2L-AS1/miR-874-3p/CCNE1 axis can modulate the initiation and progression of CRC.

Radio-frequency Dark Photon Dark Matter across the Sun.

The Dark photon as an ultralight dark matter candidate can interact with the standard model particles via kinetic mixing. We propose to search for the ultralight dark photon dark matter using radio telescopes with solar observations. The dark photon dark matter can efficiently convert into photons in the outermost region of the solar atmosphere, the solar corona, where the plasma mass of photons is close to the dark photon rest mass. Because of the strong resonant conversion and benefiting from the short distance between the Sun and the Earth, the radio telescopes can lead the dark photon search sensitivity in the mass range of 4×10^{-8}-4×10^{-6} eV, corresponding to the frequency 10-1000 MHz. As a promising example, the low-frequency array telescope can reach the kinetic mixing ε∼10^{-13} (10^{-14}) within 1 (100) h of solar observations. The future experiment square kilometer array phase 1 can reach ε∼10^{-16}-10^{-14} with 1 h of solar observations.

Clinical Impacts and Outcomes With Possible Donor-Derived Infection in Infected Donor Liver Transplantation: A Single-Center Retrospective Study in China.

BACKGROUND: Information on possible donor-derived transmission events in China is limited. We evaluated the impacts of liver transplantation from infected deceased-donors, analyzed possible donor-derived bacterial or fungal infection events in recipients, and evaluated the etiologic agents' characteristics and cases outcomes. METHODS: A single-center observational study was performed from January 2015 to March 2017 to retrospectively collect data from deceased-donors diagnosed with infection. Clinical data were recorded for each culture-positive donor and the matched liver recipient. The microorganisms were isolated and identified, and antibiotic sensitivity testing was performed. The pathogens distribution and incidence of possible donor-derived infection (P-DDI) events were analyzed and evaluated. RESULTS: Information from 211 donors was collected. Of these, 82 donors were infected and classified as the donation after brain death category. Overall, 149 and 138 pathogens were isolated from 82 infected donors and 82 matched liver recipients, respectively. Gram-positive bacteria, Gram-negative bacteria, and fungi accounted for 42.3% (63 of 149), 46.3% (69 of 149), and 11.4% (17 of 149) of pathogens in infected donors. The incidence of multidrug-resistant bacteria was high and Acinetobacter baumannii was the most concerning species. Infections occurred within the first 2 weeks after liver transplantation with an organ from an infected donor. Compared with the noninfection recipient group, the infection recipient group experienced a longer mechanical ventilation time (P = .004) and intensive care unit stay (P = .003), a higher incidence of renal dysfunction (P = .026) and renal replacement therapy (P = .001), and higher hospital mortality (P = .015). Possible donor-derived infection was observed in 14.6% of cases. Recipients with acute-on-chronic liver failure were more prone to have P-DDI than recipients with other diseases (P = .007; odds ratio = 0.114; 95% confidence interval, .025-.529). CONCLUSIONS: When a liver recipient receives a graft from an infected deceased-donor, the postoperative incidence of infection is high and the infection interval is short. In addition, when a possible donor-derived, drug-resistant bacterial infection occurs, recipients may have serious complications and poor outcomes.

Dyadobacter bucti sp. nov., isolated from subsurface sediment.

A Gram-reaction-negative, yellow-pigmented, rod-shaped, aerobic, non-motile, non-spore-forming bacterium, designated strain QTA69T, was isolated from a subsurface sediment sample collected at the Qiangtang basin, Qinghai-Tibetan Plateau, PR China. Cells were catalase-positive and oxidase-negative. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain QTA69T was a member of the genus Dyadobacter and was closely related to Dyadobacter sediminis, Dyadobacter ginsengisoli and Dyadobacter psychrophilus with sequence similarities from 97.90 % to 96.85 %. Strain QTA69T grew at 4-35 °C, and the optimum temperature was 25-28 °C. It grew at the pH range of 6.0-9.0 (optimum, pH 7.0-8.0) and its NaCl tolerance was 0-2.0 % (optimum, 0-1.0 %). The major cellular fatty acids were summed feature 3 (iso-C15 : 0 2-OH and C 16:1ω6c/C16 : 1ω7c), iso-C15 : 0 and C16 : 1ω5c. The major respiratory quinone was MK-7 and the major polar lipid was phosphatidylethanolamine. Genome sequencing revealed a genome size of 8.41 Mbp and a G+C content of 46.87 mol%. Based on whole genome average nucleotide identity values, phenotypic data, phylogenetic data and genotypic data, strain QTA69T represents a novel species of genus Dyadobacter, for which the name Dyadobacter bucti sp. nov is proposed. The type strain is QTA69T (=CGMCC 1.13688T=KCTC 72024T).

Youhaiella tibetensis gen. nov., sp. nov., isolated from subsurface sediment.

A Gram-reaction-negative bacterial strain, designated fig4(T), was isolated from a subsurface sediment core of Qiangtang Basin permafrost in China. Cells were catalase- and oxidase-positive and rods. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain fig4(T )was a member of the family Hyphomicrobiaceae and was most closely related to members of the genera Pelagibacterium, Vasilyevaea and Devosia with 93.8-96.2% sequence similarities. The major cellular fatty acids were C16 : 0, C18 : 0, 11-methyl C18 : 1 ω7c, C19 : 0 cyclo ω8c and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The major respiratory quinone was Q-10 and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and two unknown glycolipids. The DNA G+C content was 60.7 mol%. Based on the phenotypic, phylogenetic and genotypic data, strain fig4(T) is considered to represent a novel species of a new genus in the family Hyphomicrobiaceae, for which the name Youhaiella tibetensis gen. nov., sp. nov. is proposed. The type strain is fig4(T) ( = CGMCC 1.12719(T) = JCM 19854(T)).

Simultaneous determination of bisphenols and alkylphenols in water by solid phase extraction and ultra performance liquid chromatography-tandem mass spectrometry.

To establish an analytical method for determination of four bisphenols (BPA, BPB, BPF, and BPS) and two alkylphenols (4-n-OP, 4-n-NP) in water by ultra performance liquid chromatography- tandem mass spectrometry (UPLC/MS/MS). The water samples were extracted and condensed with solid-phase extraction (SPE) using C18 cartridges and eluted by acetonitrile. Separation was carried out with Acquity BEH C8 column and detection were performed by UPLC/MS/MS. Quantification was calculated by using the internal standard BPA-d16 and 4-n-NP-d8. The linear correlation coefficients of these compounds in the range of 1.0-100.0 µg/L were all over 0.999. The minimum detectable concentrations were 0.75-1.0 ng/L, and the recoveries ranged from 87.0% to 106.9%. Relative standard deviations (RSDs) were between 1.26% and 3.67%. Applying this method to detect the source water of Chaohu Lake and drinking water of Hefei, six target compounds were detected in different levels. This method is simple with high sensitivity and selectivity, could be suitable for the determination of these compounds in source and drinking water.

Proximity hybridization induced molecular machine for signal-on electrochemical detection of α-synuclein oligomers.

α-synuclein oligomer is a marker of Parkinson's disease. The traditional enzyme-linked immunosorbent assay for α-synuclein oligomer detection is not conducive to large-scale application due to its time-consuming, high cost and poor stability. Recently, DNA-based biosensors have been increasingly used in the detection of disease markers due to their high sensitivity, simplicity and low cost. In this study, based on the DNAzyme-driven DNA bipedal walking method, we developed a signal-on electrochemical sensor for the detection of α-syn oligomers. Bipedal DNA walkers have a larger walking area and faster walking kinetics, providing higher amplification efficiency compared to conventional DNA walkers. The DNA walker is driven via an Mg2+-dependent DNAzyme, and the binding-induced DNA walker will continuously clamp the MB, resulting in the proliferation of Fc confined near the GE surface. The linear range and limit of detection were 1 fg/mL to 10 pg/mL and 0.57 fg/mL, respectively. The proposed signal-on electrochemical sensing strategy is more selective. It will play a significant role in the sensitive and precise electrochemical analysis of other proteins.

Sucking lollipop after awakening from sevoflurane anesthesia reduces the degree of emergence agitation in children undergoing ambulatory surgery: A prospective randomized controlled trial.

BACKGROUND: Emergence agitation (EA) is a common complication in pediatric anesthesia, especially in preschool children maintained by sevoflurane, with incidence ranging up to 80%. The purpose of the study was to determine whether sucking lollipop after awakening from sevoflurane anesthesia reduced the degree of EA in children undergoing ambulatory surgery. METHODS: In this prospective study, 40 children aged 2 to 6 years scheduled for ambulatory surgery with sevoflurane were enrolled. They were randomly allocated to 1 of 2 groups after evaluating baseline EA levels using the pediatric anesthesia emergence delirium (PAED) scale immediately after awakening from general anesthesia: group L (sucking lollipop) or group C (control group, without sucking lollipop). The primary outcome was the overall PAED score after intervention. Pain score, parental satisfaction, the incidence of propofol rescue and negative postoperative behavioral changes (NPOBCs) were assessed. RESULTS: The overall PAED score after intervention was significantly lower in Group L compared with Group C, with an estimated difference of -1.857 (95% CI, -2.884 to -0.831; P < .001) using generalized estimating equations. However, no significant intergroup differences were observed in the pain score, parental satisfaction, the incidence of propofol rescue and NPOBCs. CONCLUSIONS: Sucking lollipop after awakening from sevoflurane anesthesia reduced the degree EA in children undergoing ambulatory surgery.

Establishment of FAP-overexpressing Cells for FAP-targeted Theranostics.

OBJECTIVE: Fibroblast activation protein (FAP) has been widely studied and exploited for its clinical applications. One of the difficulties in interpreting reports of FAP-targeted theranostics is due to the lack of accurate controls, making the results less specific and less confirmative. This study aimed to establish a pair of cell lines, in which one highly expresses FAP (HT1080-hFAP) and the other has no detectable FAP (HT1080-vec) as control, to accurately evaluate the specificity of the FAP-targeted theranostics in vitro and in vivo. METHODS: The cell lines of the experimental group (HT1080-hFAP) and no-load group (HT1080-vec) were obtained by molecular construction of the recombinant plasmid pIRES-hFAP. The expression of hFAP in HT1080 cells was detected by PCR, Western blotting and flow cytometry. CCK-8, Matrigel transwell invasion assay, scratch test, flow cytometry and immunofluorescence were used to verify the physiological function of FAP. The activities of human dipeptidyl peptidase (DPP) and human endopeptidase (EP) were detected by ELISA in HT1080-hFAP cells. PET imaging was performed in bilateral tumor-bearing nude mice models to evaluate the specificity of FAP. RESULTS: RT-PCR and Western blotting demonstrated the mRNA and protein expression of hFAP in HT1080-hFAP cells but not in HT1080-vec cells. Flow cytometry confirmed that nearly 95% of the HT1080-hFAP cells were FAP positive. The engineered hFAP on HT1080 cells had its ability to retain enzymatic activities and a variety of biological functions, including internalization, proliferation-, migration-, and invasion-promoting activities. The HT1080-hFAP xenografted tumors in nude mice bound and took up 68GA-FAPI-04 with superior selectivity. High image contrast and tumor-organ ratio were obtained by PET imaging. The HT1080-hFAP tumor retained the radiotracer for at least 60 min. CONCLUSION: This pair of HT1080 cell lines was successfully established, making it feasible for accurate evaluation and visualization of therapeutic and diagnostic agents targeting the hFAP.

Long non-coding RNA rhabdomyosarcoma 2-associated transcript contributes to neuropathic pain by recruiting HuR to stabilize DNA methyltransferase 3 alpha mRNA expression in dorsal root ganglion neuron.

Introduction: Long non-coding RNAs (lncRNAs) act as key regulators in multiple human diseases. In particular, the dysfunction of lncRNAs in dorsal root ganglion (DRG) contributes to the pathogenesis of neuropathic pain (NP). Nevertheless, the role and mechanism of most lncRNAs in NP remain unclear. Methods: Two classic chronic NP models, including L4 spinal nerve ligation (SNL) model and chronic constriction injury (CCI) of the sciatic nerve, were performed. Mechanical allodynia and heat hyperalgesia were used to evaluate neuropathic pain. DRG microinjection was used to deliver agents into DRG. qRT-PCR, immunofluorescence, immunoprecipitation, western blotting, siRNA transfection, AAV transduction were performed to investigate the phenotypes and molecular basis. Results: Here, we discovered that Rmst as a lncRNA was specifically expressed in Atf3 + injured DRG neurons and significantly upregulated following peripheral nerve damage. Rmst overexpression by direct DRG injection of AAV5-Rmst causes neuropathic symptoms in the absence of nerve damage. Conversely, blocking Rmst expression in injured DRGs alleviated nerve injury-induced pain hypersensitivities and downregulated Dnmt3a expression. Furthermore, we found peripheral nerve damage induced Rmst increase could interact with RNA-binding protein HuR to stabilize the Dnmt3a mRNA. Conclusion: Our findings reveal a crucial role of Rmst in damaged DRG neurons under NP condition and provide a novel target for drug development against NP.

The neutrophil-to-lymphocyte ratio: A potential predictor of poor prognosis in adult patients with trauma and traumatic brain injury.

Purpose: This study aimed to determine the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) in critically ill trauma patients. Methods: This retrospective study involved adult trauma patients from 335 intensive care units (ICUs) at 208 hospitals stored in the eICU database. The primary outcome was ICU mortality. The lengths of ICU and hospital stay were calculated as the secondary outcomes. The multivariable logistic regression model was used to identify independent predictors of mortality. To identify the effect of the NLR on survival, a 15-day survival curve was used. Results: A total of 3,865 eligible subjects were enrolled in the study. Univariate analysis showed that patients in the group with a higher NLR were more likely to receive aggressive methods of care delivery: mechanical ventilation, vasopressor, and antibiotics ( P < 0.001 for all). The ICU, in-hospital, and 15-day mortality rates of the four groups increased in turn (P < 0.001 for all). The multivariable logistic Cox regression model indicated that a higher NLR was an independent risk factor of ICU mortality in trauma patients. ROC analysis showed that the NLR had better predictive capacity on the mortality of patients with traumatic brain injury (TBI) than those with trauma (AUC 0.725 vs. 0.681). An NLR > 7.44 was an independent risk factor for ICU death in patients with TBI (OR: 1.837, 95% CI: 1.045-3.229) and TBI victims whose NLR > 7.44 had a 15-day survival disadvantage (P = 0.005). Conclusion: A high NLR is associated with a poor prognosis in trauma patients, even worse in patients with TBI. An NLR > 7.44 is an independent risk factor for death in patients with TBI.

4-[1-(4-Hy-droxy-3-meth-oxy-benz-yl)-1H-benzimidazol-2-yl]-2-meth-oxy-phenol.

In the title mol-ecule, C(22)H(20)N(2)O(4), the dihedral angles between the benzimidazole ring system and the benzene rings are 44.26 (2) and 82.91 (2)°. Intra-molecular O-H⋯O hydrogen bonds occur. In the crystal, O-H⋯N and O-H⋯O hydrogen bonds connect the mol-ecules into a two-dimension network parallel to (10[Formula: see text]) and weak inter-molecular C-H⋯O hydrogen bonds complete the formation of a three-dimensional network.

Efficacy and Safety of Acupuncture Combined with Herbal Medicine in Treating Gouty Arthritis: Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Gouty arthritis is a common metabolic disease caused by long-term purine metabolism and elevated serum uric acid. In recent years, the incidence of gouty arthritis has been increasing year by year. As an effective method for treating gouty arthritis, acupuncture combined with herbal medicine has been widely used in clinical practice. However, the evidence for the treatment needs to be evaluated through systematic review and meta-analysis. Methods. The Cochrane Library, PubMed, Web of Science, EMBASE, China CBM database, Clinical Trials, CNKI, China Wanfang database, and VIP information database were searched from the establishment of each database to March 2021. Randomized controlled trials (RCTs) were included in the study, and the therapeutic effects of acupuncture combined with herbal medicine versus conventional therapy, or acupuncture combined with herbal medicine versus anti-inflammatory drugs, or acupuncture combined with herbal medicine versus acupuncture/herbal medicine alone were compared in the subjects with gouty arthritis. Two authors screened all references, assessed the risk of bias, and independently extracted the data. The binary outcome was summarized using 95% confidence intervals (CIs) and risk ratios (RRs). The overall quality of the evidence was assessed with hierarchy, and meta-analysis was performed with a random-effects model. RESULTS: A total of 14 randomized controlled trials (1,065 participants, 540 treatment groups, and 525 control groups) with treatment courses of 5 to 21 days were included. Acupuncture combined with herbal medicine and acupuncture was compared in three trials, acupuncture combined with herbal medicine and conventional therapy was compared in 14 of them, and acupuncture combined with herbal medicine and anti-inflammatory drugs was compared in 8 of them. The clinical efficacy (clinical symptoms, serological tests, and visual analogue scale (VAS) results) was significantly improved in the acupuncture combined with herbal medicine treatment group (P=0.0005, 95% CI 0.03 to 0.13; 687 participants; 8 trials), and the efficacy in reducing uric acid was also better (P < 0.00001; 95% CI -102.89, -68.37; 100 participants; 2 trials; evidence with moderate quality). The effect of acupuncture combined with herbal medicine was better than that of acupuncture alone (RR 1.22, 95%CI 1.06 to 1.41; 139 participants; 3 trials), the effect of acupuncture combined with herbal medicine was better than that of herbal medicine alone (RR 1.31 95%CI 1.08 to 1.57, 100 participants, 2 trials, evidence with moderate quality), and the effect of acupuncture combined with herbal medicine was better than that of colchicine (P = 0.02, RR 1.14 95%CI 1.02 to 1.27, 2 trials, evidence with moderate quality). The incidence of adverse events was considerably different between the two groups, and the acupuncture combined with herbal medicine group was significantly superior to the control group in terms of adverse events (P < 0.00001; 95% CI (0.08 to 0.32)). CONCLUSIONS: The efficacy of acupuncture combined with herbal medicine was better than conventional drug therapy in treating gouty arthritis. The study results must be interpreted with caution due to the high or unclear risk of bias of the trials included in the study. PROSPERO registration number: CRD42020202544. INPLASY registration number: 202090006.

Circulating microRNAs as novel diagnostic biomarkers and prognostic predictors for septic patients.

This study was to find out novel miRNAs whether could be used as diagnostic or prognostic biomarkers in sepsis. We used miRNAs microarray assays and further confirmed the levels of miRNAs in 151 septic patients' plasma. 56 miRNAs were up-regulated and 74 miRNAs down-regulated in septic patients compared with the healthy volunteers. But only miR-519c-5p and miR-3622b-3p were up-regulated in both septic and septic shock patients. The levels of miR-519c-5p and miR-3622b-3p were statistically higher in 151 septic patients than healthy controls on day 1. The AUC for miR-519c-5p was 0.79 (95% CI, 0.688-0.892, p = 0.001) in the diagnosis of sepsis, and the AUC for miR-3622b-3p 0.752 (95% CI, 0.622-0.881, p = 0.003). The AUC for the combination of these two miRNAs was 0.831 (95% CI, 0.74-0.923, p < 0.001). Besides, the AUC for miR-519c-5p was 0.597 (p = 0.043) in predicting 28-day mortality. MiR-519c-5p, miR-3622b-3p were novel biomarkers for diagnosing septic patients. High miR-519c-5p levels suggest a worse short-term prognosis. CLINICAL TRIAL REGISTRATION INFORMATION: Name of the registry: Diagnostic and prognostic value of circulating miRNA in patients with sepsis; Trial registration ID: ChiCTR-DDD-17013150; registered 30 October 2017; http://www.chictr.org.cn/edit.aspx?pid=22528&htm=4.

Advances in Experimental and Clinical Research of the Gouty Arthritis Treatment with Traditional Chinese Medicine.

Gouty arthritis (GA) is a multifactorial disease whose pathogenesis is utterly complex, and the current clinical treatment methods cannot wholly prevent GA development. Western medicine is the primary treatment strategy for gouty arthritis, but it owns an unfavorable prognosis. Therefore, the prevention and treatment of GA are essential. In China, traditional Chinese medicine (TCM) has been adopted for GA prevention and treatment for thousands of years. Gout patients are usually treated with TCM according to their different conditions, and long-term results can be achieved by improving their physical condition. And TCM has been proved to be an effective method to treat gout in modern China. Nevertheless, the pharmacological mechanism of TCM for gout is still unclear, which limits its spread. The theory of prevention and treatment of gout with TCM is more well acknowledged in China than in abroad. In this article, Chinese herbs and ancient formula for gout were summarized first. A total of more than 570 studies published from 2004 to June 2021 in PubMed, Medline, CNKI, VIP, Web of Science databases and Chinese Pharmacopoeia and traditional Chinese books were searched; the current status of TCM in the treatment of GA was summarized from the following aspects: articular chondrocyte apoptosis inhibition, antioxidative stress response, inflammatory cytokine levels regulation, uric acid excretion promotion, immune function regulation, uric acid reduction, and intestinal flora improvement in subjects with gout. The literature review concluded that TCM has a specific curative effect on the prevention and treatment of GA, particularly when combined with modern medical approaches. However, lacking a uniform definition of GA syndrome differentiation and the support of evidence-based medicine in clinical practice have provoked considerable concern in previous studies, which needs to be addressed in future research.

[Effect of sorafenib on lymphangiogenesis in subcutaneously transplanted human cholangiocarcinoma in nude mice].

OBJECTIVE: To study the effects of sorafenib on lymphangiogenesis in transplanted human cholangiocarcinoma in nude mice. METHODS: The model of transplanted human cholangiocarcinoma in nude mice was established by subcutaneous inoculation of cholangiocarcinoma cell line QBC 939 cells. Thirty-six nude mice were randomly divided into 3 groups after tumor formation: control group, sorafenib 30 mg × kg⁻¹ × d⁻¹ group and sorafenib 60 mg × kg⁻¹ × d⁻¹ group (n = 12 each), and then treated by gavage for 6 weeks. The tumor growth of the dose groups and control group was measured with calipers. Using immunohistochemical staining, the lymphatic microvessels at tumor edge were marked by LYVE-1 and counted. The expression of VEGFR-3 mRNA in paracancerous tissues was evaluated by RT-PCR. RESULTS: Sorafenib significantly depressed the growth of cholangiocarcinoma. The inhibitory rate in the sorafenib 30 mg × kg⁻¹ × d⁻¹ group and 60 mg × kg⁻¹ × d⁻¹ group was 55.1% and 67.9%, respectively. The LMVDs of the control group, sorafenib 30 mg × kg⁻¹ × d⁻¹ group and 60 mg × kg⁻¹ × d⁻¹ group were 11.75 ± 3.19, 6.84 ± 2.18 and 5.03 ± 1.91, respectively. The LMVD of the control group was significantly higher than that in the dose groups (P < 0.01). The relative expressions of VEGFR-3 mRNA in the control group, sorafenib 30 mg × kg⁻¹ × d⁻¹ group and 60 mg × kg⁻¹ × d⁻¹ group were 2.158 ± 0.312, 1.027 ± 0.144 and 0.736 ± 0.149, respectively. The relative expression of VEGFR-3 mRNA in the control group was significantly higher than that in the dose groups (P < 0.05). No occurrence of lymph node metastasis was found in all groups. CONCLUSION: Sorafenib can significantly inhibit the growth of xenograft cholangiocarcinoma in nude mice. Sorafenib may reduce LMVD by down-regulation of the expression of VEGF-C/D and VEGFR-3 signaling axis.

Maternal exposure to antibiotics increases the risk of infant eczema before one year of life: a meta-analysis of observational studies.

BACKGROUND: There are some conflicting evidences showing that maternal exposure to antibiotics may increase the risk of infant eczema. The present study aims to estimate the effect of prenatal antibiotics administration on infant eczema. METHODS: According to the established inclusion criteria, eligible observational studies were collected by comprehensive database search. The qualities of the included studies were assessed using the Newcastle-Ottawa Scale. Effect sizes that were adjusted by multivariable models were extracted and combined. Publication bias was evaluated by visual inspection of funnel plot. RESULTS: A total of seven observational studies were included. The qualities of the included studies were at moderate or high level. Prenatal antibiotics use was positively associated with eczema before one year of age [odds ratio (OR) = 1.93, 95% confidence interval (CI) 1.35-2.76]. In addition, antibiotics exposure in utero was likely to be related to eczema after one year of age (OR 1.21, 95% CI 0.98-1.49). The exposure to antibiotics during third trimester was not associated with infant eczema (OR 0.97, 95% CI 0.86-1.09). CONCLUSIONS: Maternal exposure to antibiotics is associated with eczema by one-year age and may have a prolonged effect on eczema after 1-year age. The influence of timing of antibiotics exposure during pregnancy needs more studies to clarify.

Pharmacokinetics of intravenous voriconazole in patients with liver dysfunction: A prospective study in the intensive care unit.

OBJECTIVES: To characterize the pharmacokinetics (PK) of intravenous voriconazole (VRC) in critically ill patients with liver dysfunction. METHODS: Patients with liver dysfunction in the intensive care unit (ICU) were included prospectively. The Child-Pugh score was used to categorize the degree of liver dysfunction. The initial intravenous VRC dosing regimen comprised a loading dose of 300 mg every 12 h for the first 24 h, followed by 200 mg every 12 h. The first PK curves (PK curve 1) were drawn within one dosing interval of the first dose for 17 patients; the second PK curves (PK curve 2) were drawn within one dosing interval after a minimum of seven doses for 12 patients. PK parameters were estimated by non-compartmental analysis. RESULTS: There were good correlations between the area under the curve (AUC0-12) of PK curve 2 and the corresponding trough concentration (C0) and peak concentration (Cmax) (r2 = 0.951 and 0.963, respectively; both p < 0.001). The median half-life (t1/2) and clearance (CL) of patients in Child-Pugh class A (n = 3), B (n = 5), and C (n = 4) of PK curve 2 were 24.4 h and 3.31 l/h, 29.1 h and 2.54 l/h, and 60.7 h and 2.04 l/h, respectively. In the different Child-Pugh classes, the CL (median) of PK curve 2 were all lower than those of PK curve 1. The apparent steady-state volume of distribution (Vss) of PK curve 1 was positively correlated with actual body weight (r2 = 0.450, p = 0.004). The median first C0 of 17 patients determined on day 5 was 5.27 (2.61) µg/ml, and 29.4% of C0 exceeded the upper limit of the therapeutic window (2-6 µg/ml). CONCLUSIONS: The CL of VRC decreased with increasing severity of liver dysfunction according to the Child-Pugh classification, along with an increased t1/2, which resulted in high plasma exposure of VRC. Adjusted dosing regimens of intravenous VRC should be established based on Child-Pugh classes for these ICU patients, and plasma concentrations should be monitored closely to avoid serious adverse events.

[Finite element analysis of bending and standing manipulation in the treatment of lumbosacral joint disorder].

OBJECTIVE: To analyze the displacement, stress and mechanism of lumbosacral joint disorder patients after bending and standing manipulation in the finite element model. METHODS: A three-dimensional finite element model of a patient with lumbosacral joint disorder was established. The finite element analysis method was used to observe and analyze the three loading conditions of the model:axial, 34 degree inclined upward and vertical upward. RESULTS: In the lumbosacral joint disorder model, the L5 vertebral body was concentrated in the middle of the lower endplate, the intervertebral disc was concentrated in the center of the intervertebral disc, and the stress of S1 and related structures were concentrated in the anterior and posterior edges of the vertebral body. After simulated manipulation, stress mainly concentrated in the anterior, posterior and central circular areas of L5 vertebral upper endplate. The posterior structures of vertebral body concentrated in the ventral part of pedicle, isthmus and dorsal part of lamina. The stress of intervertebral disc dispersed in the posterior edge of vertebral body. Displacement results:In the lumbosacral joint disorder model, the left transverse process, the upper and lower articular process and the left part of spinous process were significantly displaced to the left, and the intervertebral disc was protruded forward. After simulated manipulation, the lower notch of L5 vertebral body moved forward and upward; the area of intervertebral foramen increased; the inferior articular process of L5 vertebral body moved forward; the superior articular process of sacrum moved forward and downward; the distance of articular process joints increased; and the displacement of sacrum concentrated on the posterior edge of vertebral body and the median sacral crest. CONCLUSIONS: Successful lumbosacral joint modeling can be carried out by finite element analysis, and the mechanism of bending and erecting manipulation is clear, which is effective and safe for the treatment of lumbosacral joint disorders.