Rising pertussis cases and deaths in China: current trends and clinical solutions.

Pertussis, an acute respiratory infection caused by Bordetella pertussis, has recently experienced a dramatic increase in incidence and associated deaths in China, drawing significant clinical attention. This article retrospectively analyzes national data on pertussis incidence and mortality from 2010 to 2024, exploring potential factors contributing to this trend. It also discusses strategies for enhancing vaccination programs, improving early diagnosis and treatment, and optimizing the clinical management of high-risk infants, with the aim of addressing the challenges posed by the current pertussis epidemic.

Non-antibiotic pharmaceutical phenylbutazone binding to MexR reduces the antibiotic susceptibility of Pseudomonas aeruginosa.

Antimicrobial resistance has been an increasingly serious threat to global public health. The contribution of non-antibiotic pharmaceuticals to the development of antibiotic resistance has been overlooked. Our study found that the anti-inflammatory drug phenylbutazone could protect P. aeruginosa against antibiotic mediated killing by binding to the efflux pump regulator MexR. In this study, antibiotic activity against P. aeruginosa alone or in combination with phenylbutazone was evaluated in vitro and in vivo. Resazurin accumulation assay, transcriptomic sequencing, and PISA assay were conducted to explore the underlying mechanism for the reduced antibiotic susceptibility caused by phenylbutazone. Then EMSA, ITC, molecular dynamic simulations, and amino acid substitutions were used to investigate the interactions between phenylbutazone and MexR. We found that phenylbutazone could reduce the susceptibility of P. aeruginosa to multiple antibiotics, including parts of ß-lactams, fluoroquinolones, tetracyclines, and macrolides. Phenylbutazone could directly bind to MexR, then promote MexR dissociating from the mexA-mexR intergenic region and de-repress the expression of MexAB-OprM efflux pump. The overexpressed MexAB-OprM pump resulted in the reduced antibiotic susceptibility. And the His41 and Arg21 residues of MexR were involved in the phenylbutazone-MexR interaction. We hope this study would imply the potential risk of antibiotic resistance caused by non-antibiotic pharmaceuticals.

Seroprevalence of B. pertussis infection and the changes of specific antibody levels in health care workers during the first two years of COVID-19 in Wuhu, China.

BACKGROUND: The reported number of pertussis cases declined after the implementation of COVID-19 prevention and control measures, however, the burden of pertussis among adults in China remains largely unknown. Additionally, the waning of natural antibody level has also rarely been assessed. METHODS: A total of 762 healthcare workers (HCWs) who had underwent the health examinations in 2021 and 2022 were included. Serum anti-PT IgG and IgA levels were determined by ELISA. Recent B. pertussis infection was defined as anti-PT IgG ≥100 IU/ml and/or anti-PT IgA ≥10 IU/ml. RESULTS: In 2021, the seroprevalence of recent B. pertussis infection was 10.1 %, and those HCWs in outpatient department had a higher percentage (18.6 %), and geometric mean concentration (GMC) (6.3 IU/ml) than those in other departments. This seroprevalence decreased to 2.4 % in 2022, although the difference remained significant. In the 77 subjects with recent B. pertussis infection in 2021, anti-PT IgG was undetectable in 18 cases the following year. Majority (68/76) of the subjects with anti-PT IgA ≥10 IU/ml in 2021 no longer had detected this antibody in 2022. Among 95 pertussis cases, approximately 60.0 % of cases reported no history of cough. Among those with a documented cough history, 36 cases with suspected pertussis courses who had never been diagnosed. Prolonged cough with nocturnal exacerbation (29/38) was the most commonly reported clinical symptom, and whoop was confirmed in six cases. Uroclepsia and syncopes during the cough attacks were reported by three and one subjects, respectively. One case presented with subconjunctival hemorrhage and tensionic purpura during the course. CONCLUSIONS: The results suggested a high prevalence of B. pertussis infection among HCWs. The presence of unrecognized adult pertussis cases and the rapid waning of antibody indicate the need to improve clinical management for suspected pertussis in adults, and to updated immunization schedule after childhood program.

Detection of Bordetella spp. in children with pertussis-like illness from 2018 to 2024 in China.

OBJECTIVE: To evaluate the role of Bordetella pertussis (B. pertussis), B. parapertussis, B. holmesii, and B. bronchiseptica on pertussis resurgence in China, particularly the sharp rise since the latest winter. METHODS: Nasopharyngeal swabs collected from children with pertussis-like illness from January 2018 to March 2024 were cultured to detect B. pertussis, B. parapertussis, B. holmesii, and B. bronchiseptica, and tested for all of these except for B. bronchiseptica using a pooled real-time polymerase chain reaction (PCR) kit targeting insertion sequences ptxS1, IS481, IS1001, and hIS1001. RESULTS: Out of the collected 7732 nasopharyngeal swabs, 1531 cases tested positive for B. pertussis (19.8%, 1531/7732), and 10 cases were positive for B. parapertussis (0.1%, 10/7732). B. holmesii and B.bronchiseptica were not detected. The number of specimens and the detection rate of B. pertussis were 1709 and 26.9% (459/1709) in 2018, 1936 and 20.7% (400/1936) in 2019, which sharply declined to 308 and 11.4% (35/308) in 2020, 306 and 4.2% (13/306) in 2021, and then notably increased to 754 and 17.6% (133/754) in 2022, 1842 and 16.0% (295/1842) in 2023, 877 and 22.3% (196/877) in the first quarter of 2024. The proportion of children aged 3 to less than 6 years (preschool age) and 6 to 16 years (school age) in pertussis cases increased significantly during the study period, especially the proportion of school-aged children increased from 2.0% (9/459) in 2018 to 40.8% (80/196) in 2024. CONCLUSIONS: B. pertussis was the predominant pathogen among children with pertussis-like illness in China, with sporadic detection of B. parapertussis and no detection of B. holmesii or B.bronchiseptica. The preschool and school-age children are increasingly prevalent in B. pertussis infection cases, which may be associated with the latest rapid escalation of pertussis outbreak.

Seroprevalence of tetanus and pertussis antibodies among health care workers in Wuhu, China.

This study aimed to elucidate the seroprevalence of antibodies to tetanus and pertussis among Chinese health care workers. Blood specimens from health care workers were collected during the 2021 annual medical examination at the First People's Hospital of Wuhu. Commercial ELISA kits were employed to quantify serum IgG antibodies against tetanus toxin (anti-TT IgG) and both IgG and IgA antibodies against pertussis toxin (anti-PT IgG, anti-PT IgA). A concentration of anti-TT IgG exceeding 0.1 IU/ml was deemed seroprotective against tetanus, while concentrations of anti-PT IgG ≥ 50 IU/ml or anti-PT IgA ≥ 15 IU/ml were indicative of a prior pertussis infection. The overall seroprotective rate for anti-TT IgG stood at 10.43% (92/882), with the highest seroprotective rate (13.91%) in the 20-29 age group, followed by the 30-39 age group (10.57%), 40-49 age group (5.80%), and 50-59 age group (5.63%). Eighteen (2.04%) of the studied subjects were positive to anti-PT IgG, and the positive rate in 20-39 age group and 40-59 age group was 1.19% (8/673) and 4.78% (10/209), respectively. Thirty (3.40%) subjects displayed anti-PT IgG levels ≥100 IU/ml and/or anti-PT IgA ≥ 15 IU/ml, suggesting a recent pertussis infection within the preceding year. Over half (503/882, 57.03%) had undetectable anti-PT IgG antibodies. The majority of health care workers in China appear susceptible to tetanus and pertussis, and a significant subset has experienced pertussis infection. The implementation of booster vaccinations against these diseases for Chinese health care workers is recommended.

Adipose tissue-derived mesenchymal stromal cells attenuate acute lung injury induced by trauma and haemorrhagic shock.

BACKGROUND: Mesenchymal stromal cells (MSCs) have shown promising therapeutic options for acute lung injury (ALI) caused by multiple factors. Here, we evaluated the therapeutic potential of adipose tissue-derived mesenchymal stromal cells (ADSCs) in trauma and hemorrhagic shock (THS)-induced ALI. METHODS: ALI model induced by THS was constructed by fractures plus abdominal trauma plus acute hemorrhage plus fluid resuscitation. The ADSCs group rats were generated by injecting 2 × 106 ADSCs at 0 and 1 h after THS. The sham, ALI, and ADSCs group rats were sacrificed at 24 h after resuscitation. The changes in lung histopathology, total protein in bronchoalveolar lavage fluid (BALF), mRNA expression of pro-inflammatory/anti-inflammatory cytokines, antioxidant, and anti-apoptotic indicator, and the activity of Toll-like receptor 4 (TLR4) signaling in lung tissues were evaluated. RESULTS: Administration of the ADSCs reversed ALI induced by THS, including lung histopathological changes/scores, and BALF total protein concentration. Additionally, ADSCs therapy also significantly down-regulated mRNA expression of pro-inflammatory TNF-α, IL-1ß, and IL-6, up-regulated mRNA expression of anti-inflammatory IL-10, anti-apoptotic molecule Bcl-2, and anti-oxidative molecule HO-1 in THS rats. Furthermore, ADSCs suppressed the expression of TLR4 in lung tissue. CONCLUSION: Our data show that ADSCs administration can exert therapeutic effects on THS-induced ALI in rats and may provide beneficial in preventative strategies for ALI.

Hybrids of ß-triketone and monoterpenoids from the peels of Callistemon viminalis.

Phytoconstituents of the peels of Callistemon viminalis has been investigated for the first time. As a result, two pair of diastereomers of hybrids of ß-triketone and α-phellandrene, named viminalisones A-B (1-2) and viminalisones CD (3-4), and three known analogues were obtained. Their structures and absolute configurations were elucidated through a combination of the analysis of their MS data, NMR spectra, single-crystal X-ray diffraction, and their experimental and calculated electronic circular dichroism (ECD) spectra. All isolates were evaluated for their antimicrobial activities against Botrytis cinerea and Cutibacterium acnes. Meroterpenoid 7 exhibited antibacterial activity against Botrytis cinerea with a MIC value of 0.256 mg/mL.

Optimal treatment strategy and prognostic analysis for patients with non-metastatic pT4 colon adenocarcinoma.

Objective: This study endeavored to explore the optimal treatment strategy and conduct a prognostic analysis for patients diagnosed with pT4M0 (pathologic stage T4) colon adenocarcinoma (COAD). Methods and materials: A total of 8,843 patients diagnosed with pT4M0 COAD between January 2010 and December 2015 were included in this study from the Surveillance, Epidemiology, and End Results (SEER) database. These patients were randomly divided into a training set and an internal validation set using a 7:3 ratio. Variables that demonstrated statistical significance (P<0.05) in univariate COX regression analysis or held clinical significance were incorporated into the multivariate COX regression model. Subsequently, this model was utilized to formulate a nomogram. The predictive accuracy and discriminability of the nomogram were assessed using the C-index, area under the curve (AUC), and calibration curves. Decision curve analysis (DCA) was conducted to confirm the clinical validity of the model. Results: In the entire SEER cohort, the 3-year overall survival (OS) rate (74.22% vs. 63.20%, P<0.001) and the 3-year cancer-specific survival (CSS) rate (76.25% vs. 66.98%, P<0.001) in the surgery combined with postoperative adjuvant therapy (S+ADT) group surpassed those in the surgery (S) group. Multivariate COX regression analysis of the training set unveiled correlations between age, race, N stage, serum CEA (carcinoembryonic antigen), differentiation, number of resected lymph nodes, and treatment modalities with OS and CSS. Nomograms for OS and CSS were meticulously crafted based on these variables, achieving C-indexes of 0.692 and 0.690 in the training set, respectively. The robust predictive ability of the nomogram was further affirmed through receiver operating characteristic (ROC) and calibration curves in both the training and validation sets. Conclusion: In individuals diagnosed with pT4M0 COAD, the integration of surgery with adjuvant chemoradiotherapy demonstrated a substantial extension of long-term survival. The nomogram, which incorporated key factors such as age, race, differentiation, N stage, serum CEA level, tumor size, and the number of resected lymph nodes, stood as a dependable tool for predicting OS and CSS rates. This predictive model held promise in aiding clinicians by identifying high-risk patients and facilitating the development of personalized treatment plans.

Investigating the predictive value of vascular endothelial growth factor in the evaluation of treatment efficacy and prognosis for patients with non-surgical esophageal squamous cell carcinoma.

In this study, we aim to investigate the predictive value of serum vascular endothelial growth factor (VEGF) in evaluating treatment efficacy and long-term prognosis for patients with non-surgical esophageal squamous cell carcinoma (ESCC). The patients diagnosed with ESCC by histopathology who didn't receive surgical treatment were retrospectively analyzed. Through follow-up and prognostic analysis, we explored the value of serum VEGF changes before, during, and after radiotherapy for predicting treatment efficacy, and identified important indicators to construct the predictive model. Eighty-four patients were enrolled in this study, and the objective response rate (ORR) after treatment was 75.0%. The serum VEGF before, during and after radiotherapy were 108.2 ± 38.4, 98.6 ± 20.3 and 96.9 ± 20.0pg/ml, respectively. Staging and serum VEGF during radiotherapy were the independent factors affecting the treatment efficacy of non-surgical ESCC patients (OR=0.182 and 0.959, P<0.05). The median overall survival (OS) and progression-free survival (PFS) were 24.4 and 15.8 months. The 3-year, 5-year, 10-year OS rates and PFS rates were 35.7%, 26.2%, 14.4%, and 26.2%, 22.6%, 12.3%, respectively. By performing COX regression analysis, we found that the TNM stage, changes of VEGF after radiotherapy (∆VEGF2), and endoscopic histopathological response were the independent prognostic factors for OS and PFS (P<0.05). The R2 of the constructed prediction model was 0.328 and 0.362, and the C-index was 0.697 and 0.708, respectively. The follow-up time-dependent AUC showed that the predicted AUC was stable and greater than 0.7 as the follow-up time increased. For patients with non-surgical ESCC, those with low VEGF levels during radiotherapy had better treatment efficacy, and those with significant VEGF reduction after radiotherapy had a better prognosis. In summary, our results demonstrate that it is feasible to construct a model to evaluate and predict the efficacy and prognosis of patients with non-surgical ESCC based on serum VEGF measurement.

A Cross-Sectional Study Revealing the Emergence of Erythromycin-Resistant Bordetella pertussis Carrying ptxP3 Alleles in China.

Background: Previous limited studies have identified that Bordetella pertussis (B. pertussis) isolates circulating in China possess distinct molecular features and high rates of erythromycin-resistance (ER). Their evolution and potential impact on the prevention and control of global pertussis are worthy of attention. Methods: The present cross-sectional study involved 311 non-duplicate and unrelated B. pertussis strains isolated from Chinese children from 2017 to 2019. Their antimicrobial susceptibilities were assessed using both E-test strips and Kirby-Bauer (KB) disk diffusion methods. Seven virulence-related genes (ptxA, ptxC, ptxP, prn, fim2, fim3, and tcfA2) and the A2047G mutation in the 23S rRNA gene were detected by PCR. Based on the susceptibilities and genotypes, 50 isolates were selected for multi-locus variable-number tandem-repeat analysis (MLVA) typing and whole-genome sequencing. Results: A total of 311 B. pertussis strains were isolated from children with a median age of 4 months (interquartile range: 2-9 months). Strains carrying the ptxP1 allele were more frequent (84.9%, 264/311), were always ER (except for one strain), and were mainly related to ptxA1/ptxC1/prn1 alleles (99.6%, 263/264). The remaining 47 (15.1%) strains carried the ptxP3 allele, mainly harboring the ptxA1/ptxC2/prn2 alleles (93.6%, 44/47), and were sensitive to erythromycin (except for two strains). The two ER-ptxP3 isolates were first identified in China, belonged to MT27 and MT28 according to MLVA, and were classified into sub-lineage IVd by phylogenetic analysis of their genome sequences. This sub-lineage also includes many strains carrying the ptxP3 allele spreading in developed countries. For each tested antimicrobial, the susceptibilities judged by KB disks were consistent with those determined by E-test strips. Conclusion: The present results reveal that B. pertussis strains with the ptxP1-ER profile still dominate in China, and a few strains carrying the ptxP3 allele have acquired the A2047G mutation in the 23S rRNA gene and the ER phenotype. The surveillance of the drug susceptibility of B. pertussis is necessary for all countries, and the KB disk method can be adopted as a screening test.

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In April 2022, the United Kingdom notified the World Health Organization (WHO) of an unexpected increase of acute hepatitis of unknown origin in children. Subsequent investigations have found more than 400 cases in more than 20 countries and regions around the world. Although the potential role of adenovirus type 41 in the pathogenesis of these cases is one hypothesis, but it is probably not the only pathogenic factor, and other infectious and non-infectious causes cannot be completely ruled out. For hepatitis caused by non-hepatitis A, B, C, D and E viruses, there is a lack of systematic monitoring and research, and many unknowns still exist. According to the current etiology speculation and epidemiological characteristics of adenovirus in China, cases of acute hepatitis with unknown origin may be found in China in the future. There is also a risk of imported cases. This article systematically sorts out the reports and studies on child acute hepatitis of unknown origin, hoping to attract the attention of pediatric clinicians in China, raise awareness and vigilance, and calmly prepare for possible abnormal situations.

Case Report: Various Clinical Manifestations Caused by Varicella-Zoster Virus in a Family.

A family cluster of varicella-zoster virus (VZV) infections was reported. Four family members (two children and their parents) continuously develop varicella after the grandmother's herpes zoster. The unvaccinated 16-month-old infant and his mother developed primary varicella with atypical clinical presentation; however, his 28-year-old father presented with a typical generalized vesicular rash. His vaccinated 4-year-old sister was clinically mild, which could be defined as a breakthrough varicella case. They infected the same virus strain but presented various clinical forms.

Remarkable structure and luminescence regulation of a Gd2LuAl5O12:Ce garnet phosphor with a Ca2+/Si4+ pair for high-quality w-WLED lighting.

Doping Gd2LuAl5O12:Ce with a Ca2+/Si4+ pair produced a series of Gd1.97-xLuCaxAl5-xSixO12:0.03Ce (x = 0.0-1.2) garnet new phosphors, and remarkable regulation of the crystal structure and Ce3+ luminescence was achieved. Rietveld refinement and spectral analysis revealed that greater incorporation of Ca2+/Si4+ led to a higher lattice rigidity by cell contraction, a narrower bandgap, a longer average bond length/less distortion of the [CeO8] dodecahedron and decreased centroid shift/crystal field splitting of the Ce3+ 5d energy level. A blue-shifted 4f-5d1 transition, a narrower emission band, improved thermal stability of luminescence and a shorter fluorescence lifetime were observed with increasing Ca2+/Si4+ content. Applying the yellowish-green-emitting Gd0.77LuCa1.2Al3.8Si1.2O12:0.03Ce optimal phosphor (x = 1.2), together with a commercial CaAlSiN3:Eu red phosphor, in 450 nm-excited LED lighting produced a low CCT of ∼3625 K and a high CRI/R9 of ∼95.2/94.8, indicating that the phosphor has application potential in high-performance w-WLED.

Site-selective and cooperative doping of Gd3Al5O12:Ce garnets for structural stabilization and warm WLED lighting of low CCT and high CRI.

Synergistic doping of the metastable Gd3Al5O12:Ce garnet with a Ca2+/Hf4+ pair and Sc3+ to form Gd2.97-xCaxHfxScyAl3O12:0.03Ce (x = 0.5-2.0, y = 0.0-1.5, x + y = 2.0) solid solution was conducted for the structural stabilization and photoluminescence manipulation. The site selection of Ca2+/Hf4+/Sc3+ dopants and the effects of doping on the crystal structure, local coordination, band structure and Ce3+ luminescence were revealed in detail with the results of XRD, Rietveld refinement, TEM, and UV-Vis/photoluminescence spectroscopy. A decrease in Ca2+/Hf4+ and an increase in the Sc3+ content were observed to shrink the lattice, widen the bandgap of the garnet host, red-shift the excitation/emission wavelength, broaden the emission band and shorten the fluorescence lifetime of Ce3+. The spectral changes were rationalized by considering the local coordination and crystal field splitting of the Ce3+ 5d energy level. Application of typical Gd0.97Ca2Hf2Al3O12:0.03Ce (x = 2.0, y = 0) cyan and Gd2.47Ca0.5Hf0.5Sc1.5Al3O12:0.03Ce (x = 0.5, y = 1.5) greenish-yellow phosphors in w-WLED lighting produced low correlated color temperatures of ∼3842 and 3514 K, high color rendering indices of ∼88 and 93 and favorable luminous efficacies of ∼32.9 and 14.7 lm/W under the excitation of 395 nm n-UV and 450 nm blue LED chips, respectively.

Acylphloroglucinol trimers from Callistemon salignus seeds: Isolation, configurational assignment, hAChE inhibitory effects, and molecular docking studies.

Alzheimer's disease (AD) diagnoses are greatly increasing in frequency as the global population ages, highlighting an urgent need for new anti-AD strategies. With the aim to search for human acetylcholinesterase (hAChE) inhibitors from the species of Myrtaceae family, ten acylphloroglucinol trimers (APTs), including eight new APTs, callistemontrimers A-H (1a, 1b, 2a, 2b, 3a, 3b, 4b, and 5b), and two naturally occurring ones (4a and 5a), along with one reported triketone-acylphloroglucinol-monoterpene adduct (6), were obtained and structurally characterized from the hAChE inhibitory acetone extract of Callistemon salignus seeds. The structures and their absolute configurations for new APTs were unequivocally established via the detailed interpretation of extensive spectroscopic data (HRESIMS and NMR), ECD calculations, and single crystal X-ray diffraction, whereas the absolute configurations of known APTs were determined by further chiral separation, and calculated ECD calculations. The results of hAChE inhibitory assay revealed that an enantiomeric mixture of 2a/2b, 2a, and 2b are good hAChE inhibitors with IC50 values of 1.22 ±â€¯0.23, 2.28 ±â€¯0.19, and 4.96 ±â€¯0.39 µM, respectively. Molecular docking was used to uncover the modes of interactions for bioactive compounds with the active site of hAChE. In addition, 2 and 6 displayed moderate neurite outgrowth-promoting effects with differentiation rates of 6.16% and 6.19% at a concentration of 1.0 µM, respectively.

New Cytotoxic Cytochalasans from a Plant-Associated Fungus Chaetomium globosum kz-19.

Four new cytochalasans, phychaetoglobins A-D (1-4), together with twelve known cytochalasans (5-16), were isolated from a mangrove-associated fungus Chaetomium globosum kz-19. The new structures were elucidated on the basis of extensive 1D and 2D NMR, HR ESIMS spectroscopic analyses, and electronic circular dichroism (ECD) calculations. The absolute configuration of 2 was established by application of Mosher's method. Compounds 4-8 exhibited moderate cytotoxicities against A549 and HeLa cell lines with the IC50 values less than 20 µM.

MicroRNA-410 serves as a candidate biomarker in hypoxic-ischemic encephalopathy newborns and provides neuroprotection in oxygen-glucose deprivation-injured PC12 and SH-SY5Y cells.

BACKGROUND: MicroRNA-410 (miR-410) has been found to be deregulated in neonatal hypoxic-ischemic encephalopathy (HIE). However, the clinical significance and biological function of miR-410 remain largely elusive. This study aims to investigate the expression and diagnostic performance of miR-410 in HIE newborns, and explores the neuroprotective effect of miR-410 in an oxygen-glucose deprivation (OGD)-induced cell injury model. METHODS: Expression of miR-410 was examined using quantitative real-time PCR, and its diagnostic performance was evaluated using a receiver operating characteristic analysis. We used OGD-injured PC12 and SH-SY5Y cells to construct an in vitro HIE model. The effect of miR-410 on OGD-induced cell injury was analyzed by assessing cell viability and apoptosis. Enzyme-linked immunosorbent assay was used to evaluate inflammation in cell model. A target gene was assessed according to the luciferase reporter assay. RESULTS: Serum miR-410 expression was significantly decreased in HIE newborns and OGD-injured cell model. The reduced miR-410 expression served as a biomarker for the diagnosis and progression of HIE. The OGD-induced impaired cell viability, enhanced cell apoptosis, and activated neuroinflammation were abrogated by the overexpression of miR-140 in both PC12 and SH-SY5S cells. Regarding the mechanisms underlying the function of miR-410, phosphatase and tensin homolog (PTEN) was proposed as a direct target of miR-410. CONCLUSION: All data revealed that serum downregulated miR-410 in HIE serves as candidate diagnostic biomarker, and that miR-410 exerts a neuroprotective role in OGD-injured cells by improving cell viability and inhibiting cell apoptosis through targeting PTEN.