Serotype distribution and antimicrobial resistance of pediatric Streptococcus pneumoniae isolated from inpatients and outpatients at Beijing Children's Hospital.

BACKGROUND: Understanding the epidemiology of Streptococcus pneumoniae (S. pneumoniae) isolates is important for pneumonia treatment and prevention. This research aimed to explore the epidemiological characteristics of S. pneumoniae isolated from pediatric inpatients and outpatients during the same period. METHODS: S. pneumoniae were isolated from unsterile samples of inpatients and outpatients younger than five years old between March 2013 and February 2014. The serotypes were determined using diagnostic pneumococcal antisera. The resistance of each strain to 13 antibiotics was tested using either the E-test or the disc diffusion method. The Sequence Types (STs) were analyzed via Multilocus Sequence Typing (MLST). RESULTS: The dominant serotypes obtained from inpatients were 19F (32.9 %), 19A (20.7 %), 23F (10.7 %), 6A (10.0 %), and 14 (8.6 %), while those from outpatients were 19F (13.6 %), 23F (12.9 %), 6A (10.0 %), 6B (10.0 %), and 19A (7.9 %). The coverage rates of 13-valent Pneumococcal Conjugate Vaccine (PCV) formulations were high in both groups. The nonsusceptibility to penicillin, cefuroxime, imipenem, erythromycin, and trimethoprim-sulfamethoxazole among the inpatient isolates was 7.1 %, 92.8 %, 65.7 %, 100 %, and 85.0 %, respectively, while that among the outpatient isolates was 0.7 %, 50.0 %, 38.6 %, 96.4 %, and 65.7 %, respectively. There were 45 and 81 STs detected from the pneumococci isolated from inpatients and outpatients, respectively. CC271 was common among both inpatients and outpatients (43.6 % and 14.3 %). CONCLUSIONS: Pneumococcal vaccine-related serotypes are prevalent among both inpatients and outpatients, especially among inpatients, who exhibit more severe antibiotic resistance. Therefore, universal immunization with PCV13 would decrease the hospitalization rate due to S. pneumoniae and the antibiotic resistance rate of S. pneumoniae.

[Quality status of Bombyx Batryticatus and suggestions for Chinese Pharmacopoeia (2025)].

To understand the current quality status and rearing situation of Bombyx Batryticatus, the authors collected 102 batches of Bombyx Batryticatus from different main producing areas and five major Chinese medicine markets from 2016 to 2018, and measured the properties and quality of the silk gland, to clarify the quality status of Bombyx Batryticatus from different producing areas and markets. In addition, 35 batches of Bombyx Batryticatus from 2019 to 2022 were used to verify the silk gland after revision. Moreover, Beauveria Bassiana was inoculated in the silkworm of 4-5 instars, and standardized rearing was carried out until they die. The death rate and the quality of Bombyx Batryticatus were measured to determine the differences in Bombyx Batryticatus of different instars, and explore the rationality of the infection age of Bombyx Batryticatus in Chinese Pharmacopoeia(2020). The results revealed that in the 102 batches of Bombyx Batryticatus, the qualification rate of silk gland was low; the content of total ash far exceeded the standard; the content of beauvericin varied greatly. The qualification rate of the silk gland of the 35 batches of Bombyx Batryticatus was only 47.49%, which could be increased to 73.00% if the number of silk gland was 2 to 4. The death rate of Bombyx Batryticatus at different infection ages was quite different, with uneven quality. Generally, the yield of Bombyx Batryticatus inoculated on the first day of the fifth instar was high with good quality. Therefore, in combination with the quality and actual production of Bombyx Batryticatus, the following suggestions were proposed for revision of Bombyx Batryticatus in Chinese Pharmacopoeia(2025): The number of silk gland should be revised as 2-4 bright brown or bright black silk glands, after which, the quality of Bombyx Batryticatus could be guaranteed, and the "quality identification based on character" could also be reflected scientifically; the content determination index that the content of beauvericin shall not be less than 0.017% should be added to better control the quality of Bombyx Batryticatus; the infection age should be revised as the first day of the fifth instar to narrow the age span, which could better fit the actual production and ensure the quality of Bombyx Batryticatus.

GuiLu-ErXian Glue extract promotes mesenchymal stem cells (MSC)-Induced chondrogenesis via exosomes release and delays aging in the MSC senescence process.

ETHNOPHARMACOLOGICAL RELEVANCE: The treatment of osteoarthritis (OA) patients is a challenging problem. Mesenchymal stem cells (MSCs) are multipotent cells and play key roles in regenerative medicine for cartilage degeneration. GuiLu-ErXian Glue (GLEXG) is an herbal remedy widely used in traditional Chinese medicine to treat joint pain and disability in elderly OA patients. However, the mechanisms of how GLEXG affects MSCs-induced chondrogensis remains to be elucidated. AIM OF THE STUDY: The aim of this study was to investigate the effects of GLEXG on MSC-derived chondrogenesis, both in vitro and in vivo and its potential mechanisms. METHODS: Using human MSC (hMSCs) as in vitro model, the effects of HPLC-profiled GLEXG water extract on chondrogenic differentiation were investigated by 3D spheroid cultures under chondrogenesis-inducing medium (CIM) condition. The chondrogenesis process was evaluated by measuring the sphere sizes, chondrogenesis-related genes expression by reverse transcription real-time PCR that targeted type II/X collagens, SOX9, aggrecan, and protein expression by immunostaining. Anti-TGF-ß1 neutralization antibody was used for mechanistic study. Mono-iodoacetate (MIA) induced OA joint was used to evaluate the effects of GLEXG on in vivo model. MSCs-derived exosomes were purified for proteomics study and senescence process was evaluated by cumulative population doublings and senescence-associated ß-Galactosidase staining. RESULTS: The results showed that GLEXG enhanced hMSCs chondrogenesis and upregulated RNA expression of type II/X collagen, SOX9 and aggrecan at 0.1 µg/mL, 0.3 µg/mL in vitro. In vivo, GLEXG at the dose of 0.3 µg intraarticular (i.a.) injection rescued the MIA-induced cartilage defect. Proteomics and ingenuity pathway analysis obtained from MSCs-released exosomes suggested that senescence pathway was less activated in GLEXG group than in vehicle group. Besides, GLEXG was able to increase cumulative population doubling and delayed hMSCs senescence process after four passages in cultures. CONCLUSION: we conclude that GLEXG promotes in vitro MSC-induced chondrogenesis possibly via exosomes release and delays aging in the MSC senescence process and that treatment with GLEXG (0.3 µg, i.a.) rescued cartilage defects in rat OA knee model.

Diagnosis, treatment, and prevention of monkeypox in children: an experts' consensus statement.

Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment,  and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.

[Randomized Controlled Trial of the Effects of Repetitive Transcranial Magnetic Stimulation and Mirror Therapy on Phantom Limb Pain in Amputees].

Objective: To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on phantom limb pain (PLP) in amputees, and to compare the therapeutic effect with that of mirror therapy (MT). Methods: The study was designed as a randomized controlled trial. The evaluators were blinded, while the subjects and the therapists were unblinded. Subjects were randomly assigned to either the rTMS group or the MT group with a computer-generated random number table. From June 2018 to December 2020, from out of 45 amputee patients screened for the study, 30 who met the inclusion criteria were recruited for the study. All patients were recruited from the Rehabilitation Medicine Center, West China Hospital, Sichuan University. In the end, 4 patients withdrew from the study and 26 patients (12 in the rTMS group and 14 in the MT group) completed the prescribed treatment and evaluation. The rTMS group was given rTMS (1 Hz, 15 min, 5 d/week) for 2 weeks in addition to conventional rehabilitation therapy, while the MT group received MT (corresponding movements of limbs, 15 min, 5 d/week) for 2 weeks in addition to conventional rehabilitation therapy. PLP was evaluated by the Visual Analogue Scale (VAS) and Douleur Neuropathique 4 Questions (DN-4). Subjects were assessed before treatment ( t 0), immediately after the completion of the treatment ( t 1) and 3 months after the completion of the treatment ( t 2). Results: The mean age of the 26 patients was 39.73±12.64. There were 15 males and 11 females. According to the reported description of the characteristics of the PLP by the patients, the characteristics with the highest incidence were tingling, stabbing, numbing, electric shocks and burning in descending order. There was no significant difference in the incidence of PLP characteristics between the two groups ( P>0.05). The two groups had comparable baseline data, showing no significant difference in VAS and DN-4 between the two groups at t 0 ( P>0.05). At t 1 and t 2, the VAS and DN-4 scores were decreased from those of t 0, showing statistically significant difference in both groups ( P<0.01 for both scores). In the rTMS group, there was no significant difference between VAS and DN-4 scores at t 1 and those at t 2 ( P>0.05). In the MT group, the VAS and DN-4 scores at t 2 were significantly lower than those of t 1 ( P<0.05). There was no statistically significant difference between the rTMS group and MT group in the changes in pain measurements, i.e., VAS and DN-4 scores, before and after the intervention ( P>0.05). The 26 patients who completed the experiment showed no dizziness, headache, or other abnormalities during the study. Conclusion: The results of this study indicate that repetitive transcranial magnetic stimulation could improve PLP in amputees, and the improvement effect was comparable to that of mirror therapy.

Clinical characteristics, antimicrobial resistance, and risk factors for mortality in paediatric invasive pneumococcal disease in Beijing, 2012-2017.

BACKGROUND: To analyse clinical characteristics, antibiotic susceptibility, and risk factors for mortality in paediatric invasive pneumococcal disease (IPD) in Beijing. METHODS: Paediatric IPD patients in our hospital were retrospectively collected from 2012 to 2017. Clinical manifestations, laboratory tests, antimicrobial susceptibility and serotype of isolates, and risk factors for mortality of IPD were analysed. RESULTS: Overall, 186 IPD cases were enrolled. The major manifestations were meningitis (76), pneumonia with bacteraemia (60), bacteraemia without focus (21), and pneumonia with empyaema (22). Of 72 cases with underlying diseases, leukaemia (18.0%), congenital heart disease (15.3%), primary immunodeficiency disease (12.5%), nephrotic syndrome (12.5%), and cerebrospinal fluid leakage (12.5%) were most common. In total 96.9% of isolates would have been covered by the pneumococcal conjugate vaccine (PCV13), including 19F (32.8%), 19A (23.4%), 4 (17.2%), and 23F (9.4%). Nonsusceptibility rates of penicillin, cefotaxime, and cefepime among nonmeningitis patients increased between 2012 and 2017; The mortality rate was 21.5%. Meningitis, respiratory failure, multiple organ failure, and white blood cell count < 4000 cells/µL were independent risk factors for mortality. CONCLUSION: Meningitis was the most common clinical manifestation of IPD, and was frequently associated with death. Strains in the PCV13 vaccine would cover most of the cases, and so wider use of PCV13 should be considered.

Antibiotics prescription for targeted therapy of pediatric invasive pneumococcal diseases in China: a multicenter retrospective study.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. METHODS: A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. RESULTS: 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. CONCLUSIONS: Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.

Application of topical gentamicin-a new era in the treatment of genodermatosis.

BACKGROUND: The clinical use of gentamicin always lies in its antimicrobial activity in the past as an aminoglycoside antibiotic. However, in the past decade, there were considerable interests in therapeutic approaches in treating hereditary diseases. Some of the genodermatosis is caused by nonsense mutations that create premature termination codons and lead to the production of truncated or non-functional proteins. Gentamicin could induce readthrough of nonsense mutations and enable the synthesis of full-length proteins. We focus on previous publications on topical application of gentamicin and review its utility in genetic skin diseases. DATA SOURCES: We search the MEDLINE through PubMed, EMBASE databases, and the Clinical Trials Registry Platform from January 1960 to July 2020 using the key search terms "gentamicin, topical gentamicin, genodermatosis, genetic skin diseases". RESULTS: The application of gentamicin in genodermatosis yielded promising results, both in vivo and in vitro, including Nagashima-type palmoplantar keratosis, epidermolysis bullosa, Hailey-Hailey disease, hereditary hypotrichosis simplex of the scalp, etc. CONCLUSIONS: Topical gentamicin is a potential treatment option for genodermatosis caused by nonsense mutation.

Effects of mirror therapy on phantom limb sensation and phantom limb pain in amputees: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the effects of mirror therapy on phantom limb sensation and phantom limb pain in amputees. DATA SOURCES: Nine electronic databases (PubMed, EMBASE, MEDLINE, Web of Science, the Cochrane Library, CINAHL, PsycInfo, PreQuest, PEDro) were searched from their inception to May 10th, 2021. METHODS: Two authors independently selected relevant studies and extracted the data. The effect sizes were calculated under a random-effects model meta-analysis, and heterogeneity was assessed using the I2 test. The risk of bias was evaluated by the Cochrane risk of bias tool, and the methodological quality was appraised by the PEDro scale. The GRADE approach was applied to assess the confidence of the effect. RESULTS: A total of 11 RCTs involving 491 participants were included in this review and nine RCTs involving 372 participants were included in meta-analysis. The quality of these studies was from poor to good with scores ranging from 2 to 8 points according to PEDro scale. The pooled SMD showed that mirror therapy reduced the pain with a large effect size (-0.81; 95% CI = -1.36 to -0.25; P = 0.005; I2 = 82%; n = 372) compared with other methods (four covered mirror, one phantom exercise, three mental visualization, one sensorimotor exercise, one transcutaneous electrical nerve stimulation, one tactile stimuli). The quality of evidence for the outcome pain intensity was determined to be fair according to GRADE approach. CONCLUSION: There is fair-quality evidence that MT is beneficial for reducing phantom limb pain.

Antimicrobial stewardship capacity and manpower needs in the Asia Pacific.

OBJECTIVES: Antimicrobial stewardship is a strategy to combat antimicrobial resistance in hospitals. Given the burden and impact of antimicrobial resistance in the Asia Pacific, it is important to document capacity and gaps in antimicrobial stewardship programmes (ASP). We aimed to understand existing capacities and practices, and define the resources needed to establish antimicrobial stewardship where it is lacking. METHODS: An anonymous online survey, consisting of questions on antimicrobial control at country, hospital and programme levels, was circulated to healthcare providers in the field of infectious diseases and microbiology through Asian Network for Surveillance of Resistant Pathogens, ReAct Group and the Australasian Society for infectious Diseases. RESULTS: 139 participants from 16 countries or regions completed the survey. The majority of participants were adult infectious diseases physicians (61/139, 43.9%) and microbiologists (31/139, 22.3%). Participants from 7 countries reported that antimicrobials can be obtained without prescriptions. Despite the high percentage (75.5%) of respondents working in large hospitals, only 22/139 participants (15.8%) from Australia, China, Singapore, Taiwan, Thailand and Vietnam reported having more than 10 infectious diseases physicians. Hospital empiric antimicrobial guidelines for common infections were available according to 110/139 (79.1%) participants. Pre-authorisation of antimicrobials was reported by 88/113 (77.9%) respondents while prospective audit and feedback was reported by 93/114 (81.6%). Automatic stop orders and culture-guided de-escalation were reported by only 52/113 (46.0%) and 27/112 (24.1%) respectively. CONCLUSION: The survey reveals a wide range of ASP development in Asia Pacific. Establishing national workgroups and guidelines will help advance antimicrobial stewardship in this diverse region.

Extremely low frequency electromagnetic fields promote cognitive function and hippocampal neurogenesis of rats with cerebral ischemia.

Extremely low frequency electromagnetic fields (ELF-EMF) can improve the learning and memory impairment of rats with Alzheimer's disease, however, its effect on cerebral ischemia remains poorly understood. In this study, we established rat models of middle cerebral artery occlusion/reperfusion. One day after modeling, a group of rats were treated with ELF-EMF (50 Hz, 1 mT) for 2 hours daily on 28 successive days. Our results showed that rats treated with ELF-EMF required shorter swimming distances and latencies in the Morris water maze test than those of untreated rats. The number of times the platform was crossed and the time spent in the target quadrant were greater than those of untreated rats. The number of BrdU+/NeuN+ cells, representing newly born neurons, in the hippocampal subgranular zone increased more in the treated than in untreated rats. Up-regulation in the expressions of Notch1, Hes1, and Hes5 proteins, which are the key factors of the Notch signaling pathway, was greatest in the treated rats. These findings suggest that ELF-EMF can enhance hippocampal neurogenesis of rats with cerebral ischemia, possibly by affecting the Notch signaling pathway. The study was approved by the Institutional Ethics Committee of Sichuan University, China (approval No. 2019255A) on March 5, 2019.

Curcumin alleviates OGD/R-induced PC12 cell damage via repressing CCL3 and inactivating TLR4/MyD88/MAPK/NF-κB to suppress inflammation and apoptosis.

OBJECTIVES: Curcumin presents some therapeutic effects including anti-cancer and anti-inflammation. Herein, we centred on the functional role of curcumin in cerebral ischaemia injury and its potential molecular mechanisms. METHODS: Microarray analysis was used for excavating crucial genes in cerebral ischaemia. PC12 cells were subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) to imitate cerebral ischaemia/reperfusion (I/R) injury in vitro. Cell viability and apoptosis abilities were evaluated by Cell Counting Kit-8 and flow cytometry assays. qRT-PCR, Western blot and enzyme-linked immunosorbent assays were performed to assess the concentrations of related genes. KEY FINDINGS: By enquiring GEO dataset, C-C motif chemokine ligand 3 (CCL3) was profoundly upregulated in cerebral I/R injury model. And CCL3 was found to be highly expressed in PC12 cells suffered from OGD/R. Moreover, we found that CCL3 was a potential target of curcumin in cerebral I/R injury. More importantly, the following experiments illustrated that curcumin inhibited the expression of CCL3 in OGD/R model and reduced cell apoptosis and inflammation. Moreover, high expression levels of TLR4, MyD88, p-NF-κB P65, p-P38 MAPK and p-IκBα in OGD/R model were inhibited by curcumin. CONCLUSIONS: Our study manifested that curcumin might be a meritorious drug for the treatment of cerebral ischaemia by acting on CCL3.

Updated diagnosis, treatment and prevention of COVID-19 in children: experts' consensus statement (condensed version of the second edition).

In the early February, 2020, we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.

Clinical characteristics, molecular epidemiology and antimicrobial susceptibility of pertussis among children in southern China.

BACKGROUND: Increasing numbers of pertussis cases have been reported in recent years. The reported cases from Shenzhen Children's Hospital were close to one tenth of all cases in China. The epidemiology of antigenic genotype and antibiotic resistance of circulating strains in children have been unknown in Shenzhen, southern China. The aim of this study was to describe the clinical features and explore the genotypes and antimicrobial susceptibility of circulating Bordetella pertussis among children in Shenzhen. METHODS: Data of hospitalized children with pertussis in Shenzhen Children's Hospital from August 2015 to April 2017 were collected. The genetic variability of isolates was investigated and Etest was performed for phenotypic susceptibility to erythromycin, azithromycin, clarithromycin, clindamycin, and trimethoprim/sulfamethoxazole. RESULTS: 469 children with pertussis confirmed by real-time quantitative polymerase chain reaction were hospitalized and strains were isolated from 105 patients. White blood cell count ≥ 20 × 109/L and lymphocyte proportion ≥ 60% were observed in 39.29% of infants younger than 3 months. The two predominant profiles of virulence-associated allelic genes were ptxA1/ptxC1/ptxP1/prn1 (48.6%) and ptxA1/ptxC2/ptxP3/prn2 (44.8%). Among the isolates, 48.6% (51/105) were found resistant to macrolides. CONCLUSIONS: These findings indicate that leukocytosis is not a sensitive indicator of pertussis. Isolates with the gene profile ptxP3/prn2 were highly circulating in Shenzhen and less resistant to macrolides, different from patterns observed in other parts of China.