VNP20009-Abvec-Igκ-MIIP suppresses ovarian cancer progression by modulating Ras/MEK/ERK signaling pathway.

Ovarian cancer poses a significant threat to women's health, with conventional treatment methods encountering numerous limitations, and the emerging engineered bacterial anti-tumor strategies offer newfound hope for ovarian cancer treatment. In this study, we constructed the VNP20009-Abvec-Igκ-MIIP (VM) engineered strain and conducted initial assessments of its in vitro growth performance and the expression capability of migration/invasion inhibitory protein (MIIP). Subsequently, ID8 ovarian cancer cells and mouse cancer models were conducted to investigate the impact of VM on ovarian cancer. Our results revealed that the VM strain demonstrated superior growth performance, successfully invaded ID8 ovarian cancer cells, and expressed MIIP, consequently suppressing cell proliferation and migration. Moreover, VM specifically targeted tumor sites and expressed MIIP which further reduced the tumor volume of ovarian cancer mice (p < 0.01), via the downregulation of epidermal growth factor receptor (EGFR), Ras, p-MEK, and p-ERK. The downregulation of the PI3K/AKT signaling pathway and the decrease in Bcl-2/Bax levels also indicated VM's apoptotic potency on ovarian cancer cells. In summary, our research demonstrated that VM exhibits promising anti-tumor effects both in vitro and in vivo, underscoring its potential for clinical treatment of ovarian cancer. KEY POINTS: • This study has constructed an engineered strain of Salmonella typhimurium capable of expressing anticancer proteins • The engineered bacteria can target and colonize tumor sites in vivo • VM can inhibit the proliferation, migration, and invasion of ovarian cancer cells.

Comparison of Azvudine and Nirmatrelvir/Ritonavir and Combined Use in Patients with COVID-19.

Purpose: To compare the effectiveness of azvudine and nirmatrelvir/ritonavir for the treatment of coronavirus disease (COVID-19). Patients and Methods: We conducted a retrospective analysis of data from 576 patients with COVID-19, comprising 195 patients without antiviral therapy, 226 patients treated with azvudine, 114 patients treated with nirmatrelvir/ritonavir, and 41 patients were treated with azvudine and nirmatrelvir/ritonavir concurrently. We compared their symptoms, mortality rates, and the length and cost of hospitalization. Results: The incidence of symptoms was similar in patients treated with azvudine and in those treated with nirmatrelvir/ritonavir. However, among patients experiencing weakness, the duration of weakness was significantly shorter in the azvudine group than in the nirmatrelvir/ritonavir group (P=0.029). Mortality did not differ significantly between the azvudine group and the nirmatrelvir/ritonavir group (18.14% vs.10.53%, P=0.068). Among "severe patients", the mortality rate was markedly lower in patients treated with nirmatrelvir/ritonavir than in patients treated with azvudine (16.92% vs.32.17%, P=0.026). In patients with hepatic insufficiency, those treated with nirmatrelvir/ritonavir had substantially lower mortality than those treated with azvudine (15.09% vs.34.25%, P=0.016). In addition, patients treated with nirmatrelvir/ritonavir had longer hospital stays (P=0.002) and higher hospital costs (P<0.001) than those receiving azvudine. Compared with patients treated with nirmatrelvir/ritonavir or azvudine alone, patients taking nirmatrelvir/ritonavir and azvudine concurrently had no significant improvement in survival (P>0.05), length of stay (P>0.05), or hospital costs (P>0.05). Conclusion: Azvudine is recommended for patients with non-severe COVID-19 with weakness. Nirmatrelvir/ritonavir is recommended for patients with severe COVID-19, to reduce mortality, and it could be the best choice for patients with hepatic insufficiency. The concurrent use of nirmatrelvir/ritonavir and azvudine in patients with COVID-19 could be not recommended.

Province-level distribution and drivers of infant mortality in mainland China: a Geodetector-based analysis of data from 2020.

OBJECTIVE: The present study investigated the province-level distribution and drivers of infant mortality rate (IMR) in mainland China. DESIGN: Ecological analysis based on publicly available data for all 31 provinces in mainland China. DATA SOURCES: Data on province-level IMRs in 2020 were obtained from the official websites of the healthcare commissions within each province and from the China Health Statistics Yearbook 2021. Data on potential IMR drivers were retrieved from the China Statistical Yearbook 2021. DATA ANALYSIS: GeoDa V.1.12.1 and ArcMap V.10.2 software were used to examine province-level distribution of IMR. Global and local spatial autocorrelations were performed, and Getis-ord G* hotspots and coldspots were identified. Geodetector was used to analyse the individual and joint influence of drivers on IMR. RESULTS: IMRs in 2020 varied from 1.91 to 7.60 per 1000 live births across provinces. The following statistically significant drivers with q values >0.5 were identified: health literacy of the population (0.6673), male illiteracy rate (0.6433), proportion of the population older than >65 years (0.6369), per capita government health expenditure (0.6216), forest coverage rate (0.5820), per capita disposable income (0.5785), per capita number of hospitals (0.5592), per capita gross regional product (0.5410) and sulfur dioxide concentration in the atmosphere (0.5158). The following three interactions among these drivers emerged as strongest influences on province-level IMR: proportion of population >65 years ∩ per capita gross regional product (q=0.9653), forest coverage rate ∩ per capita gross regional product (0.9610) and per capita government health expenditure ∩ sulfur dioxide (0.9295). CONCLUSION: IMR in mainland China varies substantially across the country, being generally high-west and low-east. Several factors, on their own and interacting together, contribute to IMR. Policies and programmes to reduce IMR should be formulated according to local conditions and should focus on western provinces of the country.

Gut microbiota dysbiosis promotes the development of epithelial ovarian cancer via regulating Hedgehog signaling pathway.

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, which remains a threat to female health at all ages. Hypotheses for EOC development include the continuous presence of inflammation, in which microbiota and inflammatory cytokines participate in cancer-related signaling pathway activation. Hedgehog (Hh) signaling is prominent for EOC progression, and interacts with inflammation response related to gut microbiota (GM). However, the precise roles of GM during this process are unknown. Here, we showed that the GM from patients with EOC differed from that of healthy women and had GM dysbiosis. We found that EOC modeling may lead to GM changes in mice, and it restored after the administration of GM from healthy controls, while GM from patients with EOC further exacerbated GM dysbiosis. Furthermore, we found that GM from EOC markedly promoted tumor progression and activated Hh signaling; meanwhile, it increased the extent of inflammation and activated NF-κB signaling, but GM from healthy controls improved them. Our results demonstrate how GM dysbiosis promoted EOC progression by activating Hh signaling mediated by TLR4/NF-κB signaling. We anticipate our assay to be a new thought for exploring the role of GM in EOC development. Furthermore, improving GM dysbiosis is a novel therapeutic approach for delaying EOC development.

Characteristics of patients with SARS-COV-2 PCR re-positivity after recovering from COVID-19.

The purpose of this study was to analyse the clinical characteristics of patients with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) PCR re-positivity after recovering from coronavirus disease 2019 (COVID-19). Patients (n = 1391) from Guangzhou, China, who had recovered from COVID-19 were recruited between 7 September 2021 and 11 March 2022. Data on epidemiology, symptoms, laboratory test results and treatment were analysed. In this study, 42.7% of recovered patients had re-positive result. Most re-positive patients were asymptomatic, did not have severe comorbidities, and were not contagious. The re-positivity rate was 39%, 46%, 11% and 25% in patients who had received inactivated, mRNA, adenovirus vector and recombinant subunit vaccines, respectively. Seven independent risk factors for testing re-positive were identified, and a predictive model was constructed using these variables. The predictors of re-positivity were COVID-19 vaccination status, previous SARs-CoV-12 infection prior to the most recent episode, renal function, SARS-CoV-2 IgG and IgM antibody levels and white blood cell count. The predictive model could benefit the control of the spread of COVID-19.

Psychological Distress and Physical Adverse Events of COVID-19 Vaccination among Healthcare Workers in Taiwan.

The COVID-19 pandemic places high pressure on everyone, including healthcare workers (HCWs), thus causing them to experience psychological distress. HCWs have priority in receiving the COVID-19 vaccine. However, few studies have identified adverse events (AEs) and psychological distress in the HCWs group. Therefore, we investigated the association between psychological distress and AEs and the determinants of protective behaviors in Taiwanese HCWs. A longitudinal measurement was conducted among HCWs at National Cheng Kung University Hospital (NCKUH), Tainan, Taiwan (n = 483, mean age = 37.55 years). All HCWs completed an online questionnaire on psychological distress, COVID-19 vaccination AEs, and protective behaviors. We used generalized estimating equations (GEE) to analyze the correlation between psychological distress and AEs, and used multivariable logistic regressions to explore the predictors of protective behaviors. Depression and distress and anger were significantly associated with various physical AEs (p = 0.045 to p < 0.001). Suicidal thoughts became a significant independent variable of systemic AEs after COVID-19 vaccination (p = 0.014 to p < 0.001). People of older ages or females engaged more in washing their hands, wearing masks, and reducing their presence in crowded places. Suicidal thoughts were related to the occurrence of systemic AEs among HCWs. Doctors performed better at preventive behaviors compared to nurses and other HCWs. HCWs who experienced anxiety and nervousness tended to avoid crowds.

Characteristics of rectal chlamydia among men who have sex with men in southern Taiwan, 2020-2022: An emerging threat of rectal lymphogranuloma venereum L2b.

BACKGROUND: The prevalence of rectal chlamydia among men who have sex with men (MSM) without human deficiency virus infection (non-HIV) remains uncertain in Taiwan, and rectal lymphogranuloma venereum (LGV) among MSM has never been reported in the Far East. MATERIAL AND METHODS: From January 2020 to April 2022, MSM coming for anonymous voluntary counseling and testing, for pre-exposure prophylaxis, and for antiretroviral therapy were enrolled. All participants submitted his fecal samples and completed a QR-code questionnaire. Medical records of those who took regular medical visits for HIV were recorded. Multiplex polymerase chain reaction (PCR) was performed for all fecal samples, and ompA gene sequencing was therefore performed for each Chlamydia-positive fecal sample. RESULTS: Among 341 MSM during 2020-2022 in southern Taiwan, 21 (6.2%) had rectal chlamydia infection. Risk factors of rectal chlamydia included co-infection with rectal gonorrhea (adjusted odds ratio [AOR] 6.78, 95% confidence interval [CI] 1.44-31.91, P = 0.015) and multiple sexual partners (AOR 1.373, 95% CI 1.002-1.882, P = 0.048). Further ompA gene sequencing from 19 Chlamydia-positive fecal samples revealed that the prevalent genotypes or genovariants were Da (26.3%) and L2b (26.3%), followed by B (21.1%), J (14.3%), and G (9.5%). All cases of rectal LGV genovariant L2b presented as acute proctitis with diarrhea, anal pain, or discharge and were treated successfully with prolonged treatment of doxycycline. CONCLUSIONS: Rectal gonorrhea and multiple sexual partners are risk factors for rectal chlamydia. Clinicians in Taiwan should be aware of the emerging threat of rectal LGV among MSM with acute proctitis.

PDK1- and PDK2-mediated metabolic reprogramming contributes to the TGFß1-promoted stem-like properties in head and neck cancer.

BACKGROUND: Resistance to chemotherapeutic drugs is a key factor for cancer recurrence and metastases in head and neck cancer (HNC). Cancer stem cells (CSCs) in tumors have self-renewal, differentiation, and higher drug resistance capabilities, resulting in a poor prognosis for patients. In glucose metabolism, pyruvate dehydrogenase kinase (PDK) inhibits pyruvate dehydrogenase and impedes pyruvate from being metabolized into acetyl-CoA and entering the tricarboxylic acid cycle to generate energy. Studies have reported that PDK1 and PDK2 inhibition suppresses the growth, motility, and drug resistance of cancer cells. Furthermore, while TGFß1 levels are persistently elevated in HNC patients with poor prognosis, the role of PDK isoforms in the TGFß1-promoted progression and stem-like properties of HNC is unclear. METHODS: Levels of PDK1 and PDK2 were evaluated in HNC tissue microarrays by immunohistochemistry to explore potential clinical relevance. PDK1 and PDK2 were knocked down by the lentivirus shRNA system to investigate their role in TGFß1-promoted tumor progression in vitro. RESULTS: We found that PDK2 levels were increased in the later stage of HNC tissues compared to constant PDK1 expression. After PDK1 and PDK2 knockdown, we discovered increased ATP production and decreased lactate production in TGFß1-treated and untreated HNC cells. However, only PDK2 silencing significantly inhibited the clonogenic ability of HNC cells. We subsequently found that TGFß1-promoted migration and invasion capabilities were decreased in PDK1 and PDK2 knockdown cells. The tumor spheroid-forming capability, motility, CSC genes, and multidrug-resistant genes were downregulated in PDK1 and PDK2 silencing CSCs. PDK1 and PDK2 inhibition reversed cisplatin and gemcitabine resistance of CSCs, but not paclitaxel resistance. CONCLUSION: The results demonstrated that the PDK1- and PDK2-mediated Warburg effect contributes to the TGFß1-enhanced stemness properties of HNC. Therefore, PDK1 and PDK2 may serve as molecular targets for the combination therapy of HNC.

Visible Light-Induced Deoxygenation and Allylation/Vinylation of Pyridyl Ethers.

The generation of alkyl radicals by deoxygenation of unactivated ethers under visible light catalysis is a hitherto unmet challenge. Herein, we report a visible light-induced deoxygenation of pyridyl ethers via formation of their pyridinium salts. The generated benzylic radicals further react with allyl/alkenyl sulfones to provide a series of coupling products in good to moderate yields. This process is proposed to undergo a reductive quenching cycle, which was elucidated by chemical, optical, and electrical experiments.

Public Health Measures During the COVID-19 Pandemic Reduce the Spread of Other Respiratory Infectious Diseases.

Background: Public health measures (such as wearing masks, physical distancing, and isolation) have significantly reduced the spread of the coronavirus disease-2019 (COVID-19), but the impact of public health measures on other respiratory infectious diseases is unclear. Objective: To assess the correlation between public health measures and the incidence of respiratory infectious diseases in China during the COVID-19 pandemic. Methods: We collected the data from the National Health and Construction Commission in China on the number of patients with six respiratory infectious diseases (measles, tuberculosis, pertussis, scarlet fever, influenza, and mumps) from 2017 to 2020 and assessed the correlation between public health measures and the incidence of respiratory infectious diseases. Finally, we used the data of the six respiratory infectious diseases in 2021 to verify our results. Results: We found public health measures significantly reduced the incidence of measles (p = 0.002), tuberculosis (p = 0.002), pertussis (p = 0.004), scarlet fever (p = 0.002), influenza (p = 0.034), and mumps (p = 0.002) in 2020, and prevented seasonal peaks. Moreover, the effects of public health measures were most marked during the peak seasons for these infections. Of the six respiratory infectious diseases considered, tuberculosis was least affected by public health measures. Conclusion: Public health measures were very effective in reducing the incidence of respiratory infectious diseases, especially when the respiratory infectious diseases would normally have been at their peak.

First Sprayable Double-Stranded RNA-Based Biopesticide Product Targets Proteasome Subunit Beta Type-5 in Colorado Potato Beetle (Leptinotarsa decemlineata).

Colorado potato beetle (CPB, Leptinotarsa decemlineata) is a major pest of potato and other solanaceous vegetables in the Northern Hemisphere. The insect feeds on leaves and can completely defoliate crops. Because of the repeated use of single insecticide classes without rotating active ingredients, many chemicals are no longer effective in controlling CPB. Ledprona is a sprayable double-stranded RNA biopesticide with a new mode of action that triggers the RNA interference pathway. Laboratory assays with second instar larvae fed Ledprona showed a dose-response where 25×10-6g/L of dsPSMB5 caused 90% mortality after 6days of initial exposure. We also showed that exposure to Ledprona for 6h caused larval mortality and decreased target messenger RNA (mRNA) expression. Decrease in PSMB5 protein levels was observed after 48h of larval exposure to Ledprona. Both PSMB5 mRNA and protein levels did not recover over time. Ledprona efficacy was demonstrated in a whole plant greenhouse trial and performed similarly to spinosad. Ledprona, currently pending registration at EPA, represents a new biopesticide class integrated pest management and insecticide resistance management programs directed against CPB.

A randomised dose-response study of prophylactic Methoxamine infusion for preventing spinal-induced hypotension during Cesarean delivery.

BACKGROUND: α-receptor agonists have been reported to be safe and effective for treating or preventing spinal-induced hypotension during cesarean delivery. As a pure α1 adrenergic agonist, methoxamine has potential advantages of reducing myocardial oxygen consumption and protecting the heart in obstetric patients compared to phenylephrine. The aim of this study was to determine the optimal prophylactic methoxamine infusion dose that would be effective for preventing spinal-induced hypotension in 50% (ED50) and 95% (ED95) of parturients. METHODS: Eighty parturients with a singleton pregnancy scheduled for elective cesarean delivery were randomly allocated to receive prophylactic methoxamine infusion at one of four different fixed-rates: 1 µg/kg/min (group M1), 2 µg/kg/min (group M2), 3 µg/kg/min (group M3), or 4 µg/kg/min (group M4). An adequate response was defined as absence of hypotension (maternal SBP < 80% of baseline or SBP < 90 mmHg). The values for ED50 and ED95 of prophylactic methoxamine infusion were determined by probit regression model. The outcomes of maternal hemodynamics and fetal status were compared among the groups. RESULTS: The calculated ED50 and ED95 (95% confidence interval) of prophylactic methoxamine infusion dose were 2.178 (95% CI 1.564 to 2.680) µg/kg/min and 4.821 (95% CI 3.951 to 7.017) µg/kg/min, respectively. The incidence of hypotension decreased with increasing methoxamine infusion dose (15/20, 11/20, 7/20 and 2/20 in group M1, M2, M3 and M4 respectively, P <  0.001). 1-min Apgar scores and umbilical arterial PaO2 were lower but umbilical arterial PaCO2 was higher in Group M1. No difference was found in the other incidence of adverse effects and neonatal outcomes among groups. CONCLUSIONS: Under the conditions of this study, when prophylactic methoxamine infusion was given at a fixed-rate based on body weight for preventing spinal-induced hypotension in obstetric patients, the values for ED50 and ED95 were 2.178 µg/kg/min and 4.821 µg/kg/min respectively. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), registry number of clinical trial: ChiCTR-1,800,018,988 , date of registration: October 20, 2018.

The predictive ability of carotid artery corrected flow time and respirophasic variation in blood flow peak velocity measured by ultrasonography for fluid responsiveness in parturients for cesarean delivery.

BACKGROUND: Ultrasonic measurements of carotid artery corrected flow time (FTc) and respirophasic variation in blood flow peak velocity (ΔVpeak) were recently introduced to predict fluid responsiveness in non-obstetric patients. We designed the present study to evaluate the performance of these two ultrasonic indices in predicting fluid responsiveness in healthy parturients. METHODS: Seventy-five parturients undergoing elective cesarean delivery were enrolled. Carotid doppler parameters including FTc, ΔVpeak, the inferior vena cava diameter at the end of expiration (IVCexp) and inspiration (IVCins), Inferior Vena Cava Collapsibility Index (IVCCI), and Stroke Volume Index (SVI) were measured before and after fluid challenge. Fluid responsiveness was defined as a 15% or more increase in SVI as assessed by transthoracic echocardiography after the fluid challenge. RESULTS: FTc and ΔVpeak but not IVCins, IVCexp and IVCCI were proved to be two independent predictors for fluid responsiveness by multivariate logistic regression, with the odds ratios of 1.191 (95% confidence interval (CI), 1.070 to 1.326) and 0.521 (95% CI, 0.351 to 0.773). The area under the ROC curve to predict fluid responsiveness for FTc was 0.846 (95% CI, 0.751-0.940) and for ΔVpeak was 0.810 (95% CI, 0.709-0.910), which were significantly higher than those for IVCins (0.436, 95% CI, 0.300-0.572), IVCexp (0.595, 95% CI, 0.460-0.730) and IVCCI (0.548, 95% CI, 0.408-0.688). CONCLUSIONS: Compared with IVCins, IVCexp and IVCCI, FTc and ΔVpeak measured by ultrasonography seem to be the highly feasible and reliable methods to predict fluid responsiveness in parturients with spontaneous breathing undergoing elective cesarean delivery.

VGLUT2/Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain by Complete Freund's Adjuvant.

Vesicular glutamate transporter type 2 (VGLUT2) is known to play an important role in mediating heat hyperalgesia induced by inflammation. However, the underlying mechanism for this activity is poorly understood. Cyclin-dependent kinase 5 (Cdk5), serving as a key regulator in modulating release of glutamate, acted a key player in the formation of heat hyperalgesia of inflammatory pain. However, it remains unknown whether there is a bridge between Cdk5 and VGLUT2 for mediating inflammatory pain. Therefore, we designed the experiment to determine whether VGLUT2 signaling pathway is involved in inflammatory pain mediated by Cdk5 in the inflammatory pain model induced by complete Freund's adjuvant (CFA). Our results showed that the coexpression of Cdk5/VGLUT2 in small- and medium-sized neuronal cells of the dorsal root ganglion (DRG) and spinal cord between days 1 and 3 following subcutaneous injection of CFA was significantly increased. Moreover, our study revealed that the expression of VGLUT2 protein in the DRG and spinal cord was remarkably increased between days 1 and 3 following CFA injection and was significantly reduced by roscovitine, a selective antagonist of Cdk5. Additionally, p25 but not p35, an activator of Cdk5, protein was significantly increased by CFA and reduced by roscovitine. Our findings suggested that VGLUT2/Cdk5 signaling pathway contributes to inflammatory pain mediated by Cdk5/p25.

A two-step approach for systematic identification and quality evaluation of wild and introduced Anemone flaccida Fr. Schmidt (Di Wu) based on DNA barcode and UPLC-QTOF-MS/MS.

Herbal materials have both medicinal and commercial values. As such, accurate species and content identification and verification are necessary to ensure the safe and effective use for medical and commodity purposes. Herein, we introduce a two-step approach for systematic identification and quality evaluation of wild and introduced Anemone flaccida Fr. Schmidt (aka Di Wu) using DNA barcode and ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). To begin, a precise and rapid identification method based on internal transcribed spacer 2 (ITS2) sequence was developed to ensure the authenticity of 'Di Wu' species. Next, the major active components were fully characterized utilizing a targeted profile of oleanane-type triterpenoid saponins, which was established via UPLC-QTOF-MS/MS. As a result, 34 oleanane-type triterpenoid saponins were identified or characterized in 'Di Wu.' The qualitative and relative quantitative analysis showed obvious differences between wild and introduced 'Di Wu.' Furthermore, dynamic changes in the contents of triterpenoid saponins throughout various harvesting periods were clearly explained and mid-April was identified as the appropriate harvest time. Moreover, results indicate that the contents of five main saponins (anhuienoside E, glycosideSt-I4a, hemsgiganoside B, flaccidoside II, and hederasaponin B) are more appropriate as a quality evaluation indicator than the current quality standard. The two-step approach provides a suitable strategy to evaluate the genuine quality of wild and introduced 'Di Wu,' and can be applied to the targeted analysis of other triterpenoid saponin analogues for quality evaluation. Graphical Abstract .

Comparison of the ED50 of intrathecal hyperbaric ropivacaine co-administered with or without intrathecal dexmedetomidine for cesarean section: A prospective, double-blinded, randomized dose-response trial using up-down sequential allocation method.

STUDY OBJECTIVE: Studies have showed that intrathecal dexmedetomidine as supplements to local anesthetics can improve the quality of the spinal anesthesia and reduce the local anesthetic requirement of spinal anesthesia for cesarean section. However, the magnitude of this effect has not been fully quantified. Therefore, we conducted the present study to investigate the ED50 of intrathecal hyperbaric ropivacaine with or without dexmedetomidine for cesarean section in healthy parturients. ED50 values obtained were compared to estimate the effect of intrathecal dexmedetomidine versus placebo on ropivacaine requirement. DESIGN: Single-blinded, prospective, randomized study. SETTING: Department of Anesthesia, Women's Hospital, Zhejiang University School of Medicine. PATIENTS: Sixty healthy parturients under elective cesarean section with combined spinal-epidural anesthesia were randomized into Group C (intrathecal ropivacaine alone) and Group D (intrathecal ropivacaine + 5 µg dexmedetomidine). INTERVENTIONS: The dose of intrathecal ropivacaine for the first parturient in both groups was 11 mg. An increment or decrement of 0.5 mg intrathecal ropivacaine was made for the subsequent parturient based on the effective or ineffective response of the previous parturient. Effective dose was defined as a bilateral T6 or above sensory block level was achieved within 15 min after induce of spinal anesthesia and no additional epidural anesthetics was required during surgery. The Dixon and Massay sequential method and Probit regression were applied to calculate the ED50 of intrathecal ropivacaine in both groups. MEASUREMENTS: Characteristics of spinal anesthesia and side effects were recorded. MAIN RESULTS: The ED50 of hyperbaric ropivacaine calculated by Dixon and Massay formula was 11.4 mg (95% CI, 11.1-11.7 mg) in Group C, and 9.4 mg (95% CI, 9.0-9.7 mg) in Group D (P < 0.05). While using the Probit regression, the ED50 of intrathecal hyperbaric ropivacaine was 11.1 mg (95% CI, 10.7-11.6 mg) in Group C, and 9.1 mg (95% CI, 8.6-9.5 mg) in Group D. Shivering was less observed in Group D than in Group C (P < 0.05). There was no significant difference in the onset time of sensory block or motor block, the incidence of hypotension, bradycardia, nausea and vomiting, sedation and pruritus between the two groups. CONCLUSION: Under the conditions of the present study, intrathecal dexmedetomidine (5 µg) reduced the ED50 of intrathecal hyperbaric ropivacaine by approximately 18% for cesarean section in healthy parturients under combined spinal-epidural anesthesia.

The complete chloroplast genome of a medicinal plant Anemone flaccida (Ranunculaceae).

Anemone flaccida has long-term been used in Chinese traditional medicine with the effects of anticancer, anti-inflammatory, antimicrobial properties, and immune regulation. However, the genomic information of this species is limited, which hinders its further medicinal application. In the present study, the complete chloroplast genome of A. flaccida was sequenced and assembled. The genome size was 157,614 bp in length, consisting of a pair of inverted repeat regions (IR, 31,184 bp), a large single copy (LSC, 79,055 bp), and a small single copy (SSC, 16,191 bp). A total of 138 genes were annotated, including 90 protein-coding genes, 40 tRNA genes, and eight rRNA genes. The GC content of the genome was 37.74%. A phylogenetic analysis on the basis of the whole chloroplast genome sequences further suggested a close relationship between A. flaccida, A. narcissiflora, and A. trullifolia. Collectively, the A. flaccida chloroplast genome provided new genomic resources which will improve its research and application in the future.

Postoperative Analgesic Effects of Different Doses of Epidural Hydromorphone Coadministered with Ropivacaine after Cesarean Section: A Randomized Controlled Trial.

PURPOSE: Single dose of epidural hydromorphone has been introduced to serve as an alternative method for postcesarean section analgesia. However, optimal dose of epidural hydromorphone remains unknown. Hence, we evaluated and compared the analgesic and adverse effects of postoperative different doses of epidural hydromorphone coadministered with ropivacaine after cesarean section. METHODS: Eighty term parturients with elective cesarean section under epidural anesthesia were allocated into four groups. Epidural analgesia was administered with an epidural bolus of either 0 mg (group H0), or 0.2 mg (group H1), or 0.4 mg (group H2), or 0.6 mg (group H3) hydromorphone coadministered with ropivacaine. The primary outcome was the visual analogue pain scores (VAPSs) and rescue opioid consumption (PCIA with sulfentanil) in 24 hours. Adverse effects such as respiratory depression, pruritus, nausea, and vomiting were recorded. RESULTS: The VAPSs of group H1 at 2, 4, 6, 12 h and 24 h after surgery was similar to group H0. The VAPSs of group H2 at 4 and 6 h postoperatively were significantly decreased when compared to group H0. But, the VAPSs of group H2 at 2, 12, and 24 h postoperatively were similar to those of group H0. The VAPSs of group H3 at 4, 6, 12 h, and 24 h after surgery were significantly decreased when compared to those of group H0. The total sulfentanil consumption in 24 hours was 90 ± 26 µg in group H0, 75 ± 29 µg in group H1, 54 ± 32 µg in group H2, and 15 ± 16 µg in group H0. Adverse effects were comparable in the four groups. CONCLUSIONS: Epidural administration of 0.6 mg hydromorphone coadministered with ropivacaine after cesarean section provided satisfactory pain relief with less sulfentanil consumption. This trial is registered with ChiCTR-IPR-16010026.

[Alteration of the glycan profile of serum glycoproteins during the seroconversion process in hepatitis B virus-infected patients treated with antiviral therapy and its clinical significance].

OBJECTIVE: To use a lectin microarray to study the alteration of glycan affinity profiles of serum glycoproteins during the hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) seroconversion in patients with chronic hepatitis B (CHB) following treatment with antiviral therapy,and to explore its biological significance. METHODS: CHB patients were divided into the following four groups:untreated HBeAg-positive,HBeAg seroconversion after anti-HBV therapy,HBsAg loss after anti-HBV therapy,and healthy individuals (controls).Serum samples were collected from each participant,depleted of high abundance proteins and analyzed by a lectin microarray containing 50 lectins.The lectin-affinity glycan profiles of serum proteins were partially verified by lectin blotting.Between-group differences were analyzed by one-way analysis of variance,and pairwise comparisons were carried out with the Student-Newman-Keuls (SNK) method. RESULTS: The results from the lectin microarray and lectin blotting assay showed significantly reduced affinity for 16 lectins in the untreated HBeAg-positive group compared to the control group (P less than 0.05);in addition,the specific glycan profiles of the untreated HBeAg-positive group included decreased terminal and core fructose,GalNAc alpha-Thr/Ser (T,Tn-antigen),GalNac alpha,terminal beta1-4,and beta-D galactose,bisecting and/or GlcNAc,mannose and Sia.However,the HBeAg seroconversion after anti-HBV therapy group showed enhanced binding of PSA,MPL and the above-mentioned 16 lectins (P less than 0.05),suggesting that the reduced serum glycoprotein glycan structures returned to normal or slightly higher than healthy levels after the therapy-induced seroconversion.Comparison of the group with HBsAg loss after anti-HBV therapy to the group with HBeAg seroconversion after anti-HBV therapy showed the binding ability of ten lectins (AAL,ACL,HAL,HPL,RCA-I,LEL,STL,PHA-E,NML and PCL) were weakened to near control levels and six lectins (VAL,LCA,GNL,PSA,MPL and JAC) were significantly strengthened (all P less than 0.05). These findings implied that the glycan containing terminal fructose, GalNacalpha, terminal beta1-4 galactose,and bisecting GlcNAc glycan structures dropped to near control levels, while the terminal beta-D-galactose residues and core fructose structure increased significantly. CONCLUSION: The glycan structures of serum glycoproteins are closely related to HBeAg and HBsAg seroconversion in CHB patients.It is possible that a special lectin binding glycan involving the terminal beta-D-galactose residues and core fructose may act as sugar markers associated with the disappearance of serum HBsAg during anti-HBV therapy for CHB.