LC-MS/MS methods for simultaneous determination of youkenafil and its metabolite M1 in human seminal plasma and plasma: Application to evaluate the acute effect of youkenafil on semen quality and its pharmacokinetics in human.

Youkenafil is a novel Phosphodiesterase type 5 inhibitor used for treating erectile dysfunction. N-desethyl compound of youkenafil (M1) is its main active metabolite. In this study, two methods were developed and validated for the simultaneous determination of youkenafil and M1 by HPLC-MS/MS in human matrices including seminal plasma and plasma, in which the multiple reaction monitoring and electrospray ionization in positive mode were adopted, and the deuterated youkenafil (youkenafil-d5) was selected as the internal standard. The collected semen sample was kept at room temperature for approximately 30 min until fully liquefied. The volume of the liquefied semen was measured and then divided into two parts. One part was centrifuged to obtain the seminal plasma for the content detection of youkenafil and M1, while the other part was used for routine semen analysis. The chromatographic separation was accomplished with the column of Poroshell 120 EC-C18 (5 × 2.1 mm, 2.7 µm, Agilent). Protein precipitation with methanol was used for the pretreatment of seminal plasma and plasma. The intra-run and inter-run precisions were less than 6.4 % (relative standard deviation) and accuracies were all within -4.7 %-6.8 % (relative error) in both matrices. All other validated bioanalytical parameters were within the acceptance criteria set by the FDA. The methods were successfully applied to different clinical studies of youkenafil. In the clinical study of the acute effect of youkenafil on semen quality in healthy males, the content of youkenafil in seminal plasma was extremely low. Concentrations of youkenafil and M1 in seminal plasma were lower than those in plasma, at 20.7 % and 4.49 % of the plasma concentration, respectively. There was no significant acute effect of youkenafil on semen quality. In the pharmacokinetic study of youkenafil after single dose-escalation administration, the exposure to youkenafil and M1 was non-linear with the dose in the range of 100-400 mg.

Ceftriaxone-Resistant Gonorrhea - China, 2022.

Gonorrhea is a widespread sexually transmitted infection; in 2022, China reported 96,313 cases of gonorrhea, making it the fourth most common notifiable infectious disease in the country after viral hepatitis, pulmonary tuberculosis, and syphilis. The rise in prevalence in antimicrobial-resistant strains, particularly the international spread of ceftriaxone-resistant clones, poses a formidable challenge to gonorrhea control. The China Gonococcal Resistance Surveillance Program (China-GRSP), established in 1987 and covering 19 of 34 provincial-level administrative units, continuously monitors gonococcal antimicrobial resistance. In 2022, 13 China-GRSP sentinel sites collected 2,804 gonococcal isolates, representing 2.9% of all cases reported in China, and 4.1% of cases reported in the 13 participating provinces. The prevalence of Neisseria gonorrhoeae resistance to ceftriaxone was 8.1%, approximately three times the 2017 rate of 2.9%; five provinces reported >10% ceftriaxone resistance. Resistance prevalences to cefixime, azithromycin, tetracycline, penicillin, and ciprofloxacin were 16.0%, 16.9%, 77.1%, 77.8%, and 97.6%, respectively. Only one case of spectinomycin resistance was reported. These data highlight a substantial increase in ceftriaxone resistance from 2017 to 2022. Effective diagnosis and treatment and appropriate management of sex partners are essential to protect the health of infected persons and prevent ongoing transmission of gonorrhea, including transmission of resistant strains. Identifying reasons for the spread of ceftriaxone-resistant N. gonorrhoeae in China could guide strategies, such as antibiotic stewardship, to mitigate the rising resistance rate and curb the spread of resistant strains.

Fundamental and Second-Order Superregular Breathers in Vector Fields.

We developed an exact theory of the superregular breathers (SRBs) of Manakov equations. We have shown that the vector SRBs do exist both in the cases of focusing and defocusing Manakov systems. The theory is based on the eigenvalue analysis and on finding the exact links between the SRBs and modulation instability. We have shown that in the focusing case the localized periodic initial modulation of the plane wave may excite both a single SRB and the second-order SRBs involving four fundamental breathers.

Analysis and prediction of the incidence and prevalence trends of gonorrhea in China.

To understand the epidemiological trend of gonorrhea in China from 2004 to 2021, predict the prevalence of the disease, and provide basic theory and data support for monitoring and managing gonorrhea. Gonorrhea incidence data in China from 2004 to 2021 were collected through the China Public Health Science Data Center and National Administration of Disease Prevention and Control, and the incidence and epidemiological characteristics were analyzed. Statistical analysis was performed using Joinpoint and autoregressive integrated moving average (ARIMA) models. A linear correlation model was used to analyze the correlation between gross domestic product (GDP) and the incidence rate. From 2004 to 2021, a total of 2,289,435 cases of gonorrhea were reported in China, with an average reported incidence rate of 9.46/100,000 people and a downward followed by an upward trend. Individuals with gonorrhea were primarily 20-30 y of age, with 1,034,847 cases (53.38%) from 2004 to 2018. The trend of increasing incidence was most obvious in the 10-20 age group (5,811 cases in 2004 to 12,752 cases in 2018, AAPC = 6.1, P < .001). The incidence of gonorrhea in China was negatively correlated with GDP from 2004 to 2021 (r = -0.547, P = .019). The correlation coefficient between the average incidence growth rate of each region from 2012 to 2018 and the average growth rate of regional GDP was 0.673 (P < .01). The root mean square error (RMSE) of the ARIMA model was 4.89%, showing powerful performance. There would be 97,910 gonorrhea cases in 2023 as predicted by the model.

Combined mutations of the penA with ftsX genes contribute to ceftriaxone resistance in Neisseria gonorrhoeae and peptide nucleic acids targeting these genes reverse ceftriaxone resistance.

OBJECTIVES: To investigate the gene mutations associated with ceftriaxone (CRO) resistance among gonococcal isolates, and to determine the effects of the mutated genes on CRO minimum inhibitory concentrations (MICs) with transformation assays and antisense peptide nucleic acids (asPNAs). METHODS: Ceftriaxone-resistant (CROR) and ceftriaxone-susceptible (CROS) isolates were identified using EUCAST and paired according to similarity in their MICs to other antimicrobials. The two groups of gonococci were sequenced and analysed. Mutated genes that showed a statistical difference between the two groups were transformed into gonococcal reference strains to determine their functions. AsPNAs were designed and transformed into the former transformant to further confirm the effects of the mutated genes. RESULTS: Twenty-two paired CROR and CROS isolates were obtained. The incidence of the penA-A501T and penA-G542S mutations individually, as well as combined mutations (penA-A501T and ftsX-R251H, penA-G542S and ftsX R251H), was statistically different between the two groups. The MIC of ATCC43069 (A43) increased 2 times following transformation with penA-A501T, and the MICs of A43 and ATCC49226 (A49) increased 32 times and 2 times following transformation with penA-A501T and ftsX-R251H, respectively. Antisense PNA-P3 reduced the MIC of the A43 transformant most significantly when transformed individually. PNA-P3 and PNA-F1 (asPNAs of the penA and ftsX) restored CRO susceptibility. CONCLUSIONS: PenA-A501T and penA-G542S mutations are important in CRO resistance among gonococci isolates. The ftsX-R251H mutation is also related to CRO resistance, and combined mutations of ftsX-R251H and penA-A501T comediate a significant reduction in CRO susceptibility. The combined application of PNA-P3 and PNA-F1 could effectively reverse the resistance to CRO in N. gonorrhoeae.

A Nationwide Survey on Detection of Chlamydia trachomatis in Health Facilities in China.

BACKGROUND: This study evaluated the clinical laboratory capacity for the diagnosis of Chlamydia trachomatis (CT) in China to provide recommendations to improve the diagnostic capacity and quality of this clinically important sexually transmitted disease. METHODS: An electronic questionnaire-based cross-sectional, survey study was conducted by the National Center for STD Control among different types of healthcare facilities in China from July to December 2021. RESULTS: The surveyed laboratory facilities were located in 332 cities in 31 provinces in China. A total of 4640 records from clinical laboratories were included in the data set for the final analysis. Less than half of the laboratories (41.6% [1931 of 4640]) performed the CT diagnostic test; of these, 721 laboratories (15.5% [721 of 4640]) carried out nucleic acid amplification test (NAAT) methods, and 1318 laboratories (28.4% [1318 of 4640]) performed antigen-based immunochromatographic assays. Most laboratories were equipped with biological safety cabinets (93.7% [4348 of 4640]), 49.2% (2283 of 4640) were equipped with fully automated nucleic acid extractors, and 55.2% (2560 of 4640) were equipped with polymerase chain reaction amplification instruments. The laboratories from Southern China or third-class hospitals (i.e., the highest rated hospitals) had the highest proportion using NAATs to diagnose CT among the surveyed health facilities. CONCLUSIONS: Advancing laboratories to use NAAT to detect CT should be phased step-by-step by different areas and levels of hospitals according to the current situation.

Evaluation of Neisseria gonorrhoeae Isolates Susceptibility to Antibiotics in Zhejiang Province Since 2007.

Objective: This study aimed to assess the drug susceptibility of clinical isolates of Neisseria gonorrhoeae to spectinomycin, ceftriaxone and azithromycin. Moreover, the temporal trends in the minimum inhibitory concentration (MIC) of five antibiotics from Zhejiang, China, are also in the scope of this study. Methods: A total of 1710 gonococcal clinical strains were collected between 2007 and 2021 from health-care institutions in Zhejiang. The MICs of ceftriaxone, azithromycin, spectinomycin, penicillin and ciprofloxacin were assessed by agar dilution method on 1710 Neisseria gonorrhoeae isolates. Count data were expressed as strains and rates, and MICs distribution was elucidated using descriptive statistics. Results: The total resistance rates of gonococci to azithromycin, spectinomycin, penicillin and ciprofloxacin in this study were 19.3%, 0.3%, 75.4% and 99.7%, respectively. Conclusion: The in vitro results showed a high prevalence of resistance to ciprofloxacin and penicillin. Azithromycin resistance rate has exceeded 5%, suggested a high prevalence of resistance. Ceftriaxone and spectinomycin are suggested based on this study for the treatment of Neisseria gonorrhoeae in Zhejiang.

Proteomics Reveals the Effect of Low-Intensity Focused Ultrasound on Spasticity After Spinal Cord Injury.

AIM: To explore the efficacy and possible mechanisms of Low-intensity focused ultrasound (LIFU) in alleviating spasticity caused by Spinal cord injury (SCI). MATERIAL AND METHODS: We selected male Sprague?Dawley rats as subjects and performed transverse injuries on the T9 vertebra of their spinal cord (SC) to build SCI. On the 7th day after SCI, LIFU treatment was performed below the SCI segment once a day for 20 min, for 4 consecutive weeks. During treatment, a pressure sensor was used to assess the degree of spasticity. After treatment, the SC tissues from the treatment sites of the SCI+LIFU(-) and SCI+LIFU(+) groups were extracted, and high-throughput sequencing was performed to identify the changes in proteomics. In addition, expression of the growth associated protein 43 (Gap43) was validated by western blotting. RESULTS: The behavioral results suggested that after 2 weeks of SCI, the rats were significantly induced to have a spastic reaction (p < 0.05), while after 4 weeks of LIFU treatment, the spastic response of rats was significantly improved (p < 0.05). Western blot analysis showed a significant increase in Gap43 expression in the SCI+LIFU(-) group compared with the sham group, whereas after 4 weeks of LIFU treatment, Gap43 protein expression was significantly decreased (p < 0.05). CONCLUSION: The results of this study showed that LIFU is an alternative treatment that can effectively relieve spastic reactions caused by SCI, possibly by reducing abnormal neuroplasticity or axon regeneration below the SCI segment.

Performance evaluation of eight treponemal antibody tests in China.

In this study, the performance of 8 commercially available treponemal antibody tests was evaluated. Higher specificity was achieved in the automated chemiluminescence immunoassays(CIA assays) than enzyme-linked immunosorbent (ELISA) assays, but no significant differences were found in terms of the sensitivity levels. The levels of test sensitivity did not differ by HIV status and TRUST titer but did differ by clinical stage. The results of WB-IgG revealed that the level of antibodies against the 4 antigens showed an upward trend with the development of the clinical stages of syphilis, reaching a peak in tertiary syphilis and then decreasing. The present results supported the good performance of CIA tests used in the blood source screening of syphilis, which reduced the waste of plasma. The reaction intensities of anti-TP17 and TP47 antibodies in past treated syphilis samples were considerably weak and were expected to be used for monitoring the therapeutic effect of syphilis.

Low-Intensity Focused Ultrasound Alleviates Chronic Neuropathic Pain-Induced Allodynia by Inhibiting Neuroplasticity in the Anterior Cingulate Cortex.

Low-intensity focused ultrasound (LIFU) is a potential noninvasive method to alleviate allodynia by modulating the central nervous system. However, the underlying analgesic mechanisms remain unexplored. Here, we assessed how LIFU at the anterior cingulate cortex (ACC) affects behavior response and central plasticity resulting from chronic constrictive injury (CCI). The safety of LIFU stimulation was assessed by hematoxylin and eosin (H&E) and Fluoro-Jade C (FJC) staining. A 21-day ultrasound exposure therapy was conducted from day 91 after CCI surgery in mice. We assessed the 50% mechanical withdrawal threshold (MWT50) using Von Frey filaments (VFFs). The expression levels of microtubule-associated protein 2 (MAP2), growth-associated protein 43 (GAP43), and tau were determined via western blotting (WB) and immunofluorescence (IF) staining to evaluate the central plasticity in ACC. The regions of ACC were activated effectively and safely by LIFU stimulation, which significantly increased the number of c-fos-positive cells (P < 0.05) with no bleeding, coagulative necrosis, and neuronal loss. Under chronic neuropathic pain- (CNP-) induced allodynia, MWT50 decreased significantly (P < 0.05), and overexpression of MAP2, GAP43, and tau was also observed. After 3 weeks of treatment, significant increases in MWT50 were found in the CCI+LIFU group compared with the CCI group (P < 0.05). WB and IF staining both demonstrated a significant reduction in the expression levels of MAP2, GAP43, and tau (P < 0.05). LIFU treatment on ACC can effectively attenuate CNP-evoked mechanical sensitivity to pain and reverse aberrant central plasticity.

Low-Intensity Focused Ultrasound Alleviates Spasticity and Increases Expression of the Neuronal K-Cl Cotransporter in the L4-L5 Sections of Rats Following Spinal Cord Injury.

Low-intensity focused ultrasound (LIFU) has been shown to provide effective activation of the spinal cord neurocircuits. The aim of this study was to investigate the effects of LIFU in order to alleviate spasticity following spinal cord injury (SCI) by activating the spinal neurocircuits and increasing the expression of the neuronal K-Cl cotransporter KCC2. Adult male Sprague Dawley (SD) rats (220-300 g) were randomly divided into a sham control group, a LIFU- group, and a LIFU+ group. The mechanical threshold hold (g) was used to evaluate the behavioral characteristics of spasm. Electromyography (EMG) was used to assess activation of the spinal cord neurocircuits and muscle spontaneous contraction. Spasticity was assessed by frequency-dependent depression (FDD). The expression of KCC2 of the lumbar spinal cord was determined via western blot (WB) and immunofluorescence (IF) staining. The spinal cord neurocircuits were activated by LIFU simulation, which significantly reduced the mechanical threshold (g), FDD, and EMG recordings (s) after 4 weeks of treatment. WB and IF staining both demonstrated that the expression of KCC2 was reduced in the LIFU- group (P < 0.05). After 4 weeks of LIFU stimulation, expression of KCC2 had significantly increased (P < 0.05) in the LIFU+ group compared with the LIFU- group. Thus, we hypothesized that LIFU treatment can alleviate spasticity effectively and upregulate the expression of KCC2 in the L4-L5 section of SCI rats.

A Single Amino Acid Substitution in Elongation Factor G Can Confer Low-Level Gentamicin Resistance in Neisseria gonorrhoeae.

The continued emergence of Neisseria gonorrhoeae isolates which are resistant to first-line antibiotics has reinvigorated interest in alternative therapies such as expanded use of gentamicin (Gen). We hypothesized that expanded use of Gen promotes emergence of gonococci with clinical resistance to this aminoglycoside. To understand how decreased susceptibility of gonococci to Gen might develop, we selected spontaneous low-level Gen-resistant (GenR) mutants (Gen MIC = 32 µg/mL) of the Gen-susceptible strain FA19. Consequently, we identified a novel missense mutation in fusA, which encodes elongation factor G (EF-G), causing an alanine (A) to valine (V) substitution at amino acid position 563 in domain IV of EF-G; the mutant allele was termed fusA2. Transformation analysis showed that fusA2 could increase the Gen MIC by 4-fold. While possession of fusA2 did not impair either in vitro gonococcal growth or protein synthesis, it did result in a fitness defect during experimental infection of the lower genital tract in female mice. Through bioinformatic analysis of whole-genome sequences of 10,634 international gonococcal clinical isolates, other fusA alleles were frequently detected, but genetic studies revealed that they could not decrease Gen susceptibility in a similar manner to fusA2. In contrast to these diverse international fusA alleles, the fusA2-encoded A563V substitution was detected in only a single gonococcal clinical isolate. We hypothesize that the rare occurrence of fusA2 in N. gonorrhoeae clinical isolates is likely due to a fitness cost during infection, but compensatory mutations which alleviate this fitness cost could emerge and promote GenR in global strains.

Fever, Tachypnea, and Monocyte Distribution Width Predicts Length of Stay for Patients with COVID-19: A Pioneer Study.

(1) Background: Our study investigated whether monocyte distribution width (MDW) could be used in emergency department (ED) settings as a predictor of prolonged length of stay (LOS) for patients with COVID-19. (2) Methods: A retrospective cohort study was conducted; patients presenting to the ED of an academic hospital with confirmed COVID-19 were enrolled. Multivariable logistic regression models were used to obtain the odds ratios (ORs) for predictors of an LOS of >14 days. A validation study for the association between MDW and cycle of threshold (Ct) value was performed. (3) Results: Fever > 38 °C (OR: 2.82, 95% CI, 1.13−7.02, p = 0.0259), tachypnea (OR: 4.76, 95% CI, 1.67−13.55, p = 0.0034), and MDW ≥ 21 (OR: 5.67, 95% CI, 1.19−27.10, p = 0.0269) were robust significant predictors of an LOS of >14 days. We developed a new scoring system in which patients were assigned 1 point for fever > 38 °C, 2 points for tachypnea > 20 breath/min, and 3 points for MDW ≥ 21. The optimal cutoff was a score of ≥2. MDW was negatively associated with Ct value (ß: −0.32 per day, standard error = 0.12, p = 0.0099). (4) Conclusions: Elevated MDW was associated with a prolonged LOS.

Treatment Combining Focused Ultrasound with Gastrodin Alleviates Memory Deficit and Neuropathology in an Alzheimer's Disease-Like Experimental Mouse Model.

Alzheimer's disease (AD) is the most common type of dementia but lacks effective treatment at present. Gastrodin (GAS) is a phenolic glycoside extracted from the traditional Chinese herb-Gastrodia elata-and has been reported as a potential therapeutic agent for AD. However, its efficiency is reduced for AD patients due to its limited BBB permeability. Studies have demonstrated the feasibility of opening the blood-brain barrier (BBB) via focused ultrasound (FUS) to overcome the obstacles preventing medicines from blood flow into the brain tissue. We explored the therapeutic potential of FUS-mediated BBB opening combined with GAS in an AD-like mouse model induced by unilateral intracerebroventricular (ICV) injection of Aß 1-42. Mice were divided into 5 groups: control, untreated, GAS, FUS and FUS+GAS. Combined treatment (FUS+GAS) rather than single intervention (GAS or FUS) alleviated memory deficit and neuropathology of AD-like mice. The time that mice spent in the novel arm was prolonged in the Y-maze test after 15-day intervention, and the waste-cleaning effect was remarkably increased. Contents of Aß, tau, and P-tau in the observed (also the targeted) hippocampus were reduced. BDNF, synaptophysin (SYN), and PSD-95 were upregulated in the combined group. Overall, our results demonstrate that FUS-mediated BBB opening combined with GAS injection exerts the potential to alleviate memory deficit and neuropathology in the AD-like experimental mouse model, which may be a novel strategy for AD treatment.

Gastrodin modified polyurethane conduit promotes nerve repair via optimizing Schwann cells function.

Peripheral nerve regeneration and functional recovery remain a major clinical challenge. Nerve guidance conduit (NGC) that can regulate biological behavior of Schwann cells (SCs) and facilitate axonal regeneration through microenvironmental remodeling is beneficial for nerve regeneration and functional recovery. Gastrodin, a main constituent of a Chinese traditional herbal medicine, has been known to display several biological and pharmacological properties, especially antioxidative, anti-inflammatory and nerve regeneration. Herein, polyurethane (PU) NGCs modified by different weight ratio of Gastrodin (0, 1 and 5 wt%) were designed for sequential and sustainable drug release, that created a favorable microenvironment for nerve regeneration. The scaffold showed suitable pore structure and biocompatibility in vitro, and evidently promoted morphological and functional recovery of regenerated sciatic nerves in vivo. Compared to the PU and 1%Gastrodin/PU scaffolds, the 5%Gastrodin/PU significantly enhanced the proliferation, migration and myelination of SCs and up-regulated expression of neurotrophic factors, as well as induction of the differentiation of PC12 cells. Interestingly, the obvious anti-inflammatory response was observed in 5%Gastrodin/PU by reduced expression of TNF-α and iNOS, which also evidenced by the few fibrous capsule formation in the subcutaneous implantation. Such a construct presented a similarity to autograft in vivo repairing a 10 mm sciatic nerve defects. It was able to not only boost the regenerated area of nerve and microvascular network, but also facilitate functional axons growth and remyelination, leading to highly improved functional restoration. These findings demonstrate that the 5%Gastrodin/PU NGC efficiently promotes nerve regeneration, indicating their potential for use in peripheral nerve regeneration applications.

Pharmacokinetics and Bioequivalence of a Generic Fixed-Dose Combination Tablet of Metformin Hydrochloride/Vildagliptin Versus a Branded Product in Healthy Chinese Subjects Under Fed and Fasting Conditions.

The purpose of this study was to compare the bioequivalence and safety of test and reference preparations of fixed-dose combination tablets of metformin hydrochloride/vildagliptin 850 mg/50 mg in healthy volunteers under fasting and fed conditions for marketing authorization in China. A single-dose, randomized, open-label, 2-way crossover study was conducted. Blood samples were collected up to 36 hours after dosing in each period with a 7-day washout. Pharmacokinetic parameters, including maximum plasma concentration (Cmax ), time to reach Cmax , area under the plasma concentration-time curve (AUC) from time 0 to the last time point of the measurable concentration, AUC from time 0 to infinity, terminal elimination half-life, and apparent clearance, were calculated using noncompartmental methods and compared between the 2 formulations. Safety profiles were assessed, including significant findings of vital signs, electrocardiogram, laboratory tests, physical examination, and adverse events. A total of 30 healthy subjects (19 men, 11 women) were randomized, and 29 subjects were treated under fasting conditions. Likewise, 30 subjects (24 men, 6 women) were randomized and treated under fed conditions. The geometric mean ratio and corresponding 90% confidence intervals of Cmax , AUC from time 0 to the last time point of the measurable concentration , and AUC from time 0 to infinity for both metformin hydrochloride and vildagliptin between the 2 fixed-dose combination formulations were within the bioequivalence acceptance range of 80% to 125% under fasting or fed conditions. Therefore, the generic and branded formulations were bioequivalent and well tolerated in healthy Chinese subjects.

Effects of Noninvasive Low-Intensity Focus Ultrasound Neuromodulation on Spinal Cord Neurocircuits In Vivo.

Although neurocircuits can be activated by focused ultrasound stimulation, it is unclear whether this is also true for spinal cord neurocircuits. In this study, we used low-intensity focused ultrasound (LIFU) to stimulate lumbar 4-lumbar 5 (L4-L5) segments of the spinal cord of normal Sprague Dawley rats with a clapper. The activation of the spinal cord neurocircuits enhanced soleus muscle contraction as measured by electromyography (EMG). Neuronal activation and injury were assessed by EMG, western blotting (WB), immunofluorescence, hematoxylin and eosin (H&E) staining, Nissl staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), somatosensory evoked potentials (SEPs), motor evoked potentials (MEPs), and the Basso-Beattie-Bresnahan locomotor rating scale. When the LIFU intensity was more than 0.5 MPa, LIFU stimulation induced soleus muscle contraction and increased the EMG amplitudes (P < 0.05) and the number of c-fos- and GAD65-positive cells (P < 0.05). When the LIFU intensity was 3.0 MPa, the LIFU stimulation led to spinal cord damage and decreased SEP amplitudes for electrophysiological assessment (P < 0.05); this resulted in coagulation necrosis, structural destruction, neuronal loss in the dorsal horn by H&E and Nissl staining, and increased expression of GFAP, IL-1ß, TNF-α, and caspase-3 by IHC, ELISA, and WB (P < 0.05). These results show that LIFU can activate spinal cord neurocircuits and that LIFU stimulation with an irradiation intensity ≤1.5 MPa is a safe neurostimulation method for the spinal cord.

Antimicrobial Susceptibility of Ertapenem in Neisseria gonorrhoeae Isolates Collected Within the China Gonococcal Resistance Surveillance Programme (China-GRSP) 2018.

PURPOSE: This study aimed to determine the minimum inhibitory concentrations (MICs) of ertapenem on Neisseria gonorrhoeae collected from eight Chinese provinces in 2018. METHODS: The MICs of ertapenem on 503 Neisseria gonorrhoeae isolates (415 isolates selected randomly and 88 isolates selected with preference) were measured using the agar dilution method. For comparison, the MICs of ceftriaxone and azithromycin were detected. RESULTS: Among 415 randomly selected isolates, the MIC range for ertapenem was from ≤0.008 mg/L to 0.5 mg/L. The corresponding MIC50 and MIC90 were 0.06 and 0.125 mg/L, respectively. Twelve of 415 isolates (2.9%) exhibited MIC values ≥0.25 mg/L, and only one isolate (0.2%) had a MIC of 0.5 mg/L. By comparing all 503 tested isolates, a correlation of r = 0.487 (P <0.001) between ertapenem and ceftriaxone MIC was observed, and the correlation between MICs of ertapenem and azithromycin was low (r = -0.12, P = 0.007). In 24 ceftriaxone-decreased susceptibility isolates, four isolates (16.7%) showed a MIC ≥0.25 mg/L for ertapenem. In 85 azithromycin resistant isolates, three isolates (3.5%) showed a MIC ≥0.25 mg/L for ertapenem. CONCLUSION: The in vitro results suggest that ertapenem has satisfactory susceptibility in isolates collected from eight provinces in China; hence, it might be a promising treatment option for resistant gonococcal infections.

Extreme spectral asymmetry of Akhmediev breathers and Fermi-Pasta-Ulam recurrence in a Manakov system.

The dynamics of Fermi-Pasta-Ulam (FPU) recurrence in a Manakov system is studied analytically. Exact Akhmediev breather (AB) solutions for this system are found that cannot be reduced to the ABs of a single-component nonlinear Schrödinger equation. Expansion-contraction cycle of the corresponding spectra with an infinite number of sidebands is calculated analytically using a residue theorem. A distinctive feature of these spectra is the asymmetry between positive and negative spectral modes. A practically important consequence of the spectral asymmetry is a nearly complete energy transfer from the central mode to one of the lowest-order (left or right) sidebands. Numerical simulations started with modulation instability of plane waves confirm the findings based on the exact solutions. It is also shown that the full growth-decay cycle of the AB leads to the nonlinear phase shift between the initial and final states in both components of the Manakov system. This finding shows that the final state of the FPU recurrence described by the vector ABs is not quite the same as the initial state. Our results are applicable and can be observed in a wide range of two-component physical systems such as two-component waves in optical fibers, two-directional waves in crossing seas, and two-component Bose-Einstein condensates.