Amorphous solid dispersion (ASD) is one of the most effective formulation approaches to enhance the water solubility and oral bioavailability of poorly water-soluble drugs. However, maintenance of physical stability of amorphous drug is one of the main challenges in the development of ASD. Crystallization is a process of nucleation and crystal growth. The nucleation is the key factor that influences the physical stability of the ASD. However, a theoretical framework to describe the way to inhibit the nucleation of amorphous drug is not yet available. We reviewed the methods and theories of nucleation for amorphous drug. Meanwhile, we also summarized the research progress on the mechanism of additives influence on nucleation and environmental factors on nucleation. This review aims to enhance the better understanding mechanism of nucleation of amorphous drug and controlling over the crystal nucleation during the ASD formulation development.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective: To investigate the clinical characteristics, serogroups and antimicrobial resistance of invasive non-typhoid Salmonella infection in children at Xiamen. Methods: Retrospective cohort study. The clinical manifestations, treatment, prognosis, serogroups and antimicrobial resistance of 29 hospitalized children with invasive non-typhoid Salmonella infection confirmed by blood, cerebrospinal fluid, bone marrow and other sterile body fluids or deep pus culture at the Department of Infectious Diseases, the Department of Orthopedics and the Department of General Surgery in Xiamen Children's Hospital from January 2016 to December 2021 were analyzed. According to the clinical diagnosis criteria, the patients were divided into sepsis group and non-sepsis group (bacteremia and local suppurative infection). The inflammatory markers, serogroups distribution and drug resistance were compared between the two groups. Comparison between groups using Mann-Whitney U test and χ² test. Results: Among the 29 cases, there were 17 males and 12 females, with an onset age of 14 (9, 25) months, and 10 cases (34%) of patients were younger than 1 year old, 15 cases (52%) under 1 to 3 years old, and 4 cases (14%) greater than or equal 3 years old. The onset time of 25 cases (86%) was from April to September. The diseases included 19 cases (66%) septicemia (2 of which were combined with suppurative meningitis), 10 cases (34%) non-sepsis group, including 7 cases bacteremia and 3 cases local suppurative infection (2 cases of osteomyelitis, 1 case of appendicitis with peritonitis). The clinical manifestations were fever in 29 cases (100%), diarrhea and abdominal pain in 18 cases (62%), cough and runny nose in 10 cases (34%). Eighteen cases (62%) were cured and 11 cases (38%) were improved by effective antibiotics treatment. C-reactive protein in sepsis group was significantly higher than that in non-sepsis group (25.2 (16.1, 56.4) vs. 3.4 (0.5, 7.5) mg/L, Z=-3.81, P<0.001).The serogroups of C, B and E were the most prevalent among non-typhoid Salmonella isolates, accounting for 10 cases (34%), 9 cases (31%) and 7 cases (24%) respectively. Antibacterial drug sensitivity test showed that the sensitivity rates of imipenem, ertapenem and piperaciratazobactam were all 100% (31/31), those of ceftazidime, ceftriaxone, and cefepime were 94% (29/31), 94% (29/31) and 97% (30/31) respectively. The drug resistance rates of ampicillin, ampicillin-sulbactam and trimethoprim-sulfamethoxazole were 51% (16/31), 48% (15/31) and 48% (15/31) respectively, those of cefazolin, cefotetan, tobramycin, gentamicin and amikacinwere all 100% (31/31). There were no significant differences in the drug resistance rates of ceftazidime, ceftriaxone, aztreonam, ampicillin-sulbactam, ampicillin, trimethoprim-sulfamethoxazole and ciprofloxacin between the sepsis group and the non-sepsis group (χ²=0.31,0.31,0.00,0.02,0.02,0.02,0.26, all P>0.05). Conclusions: Invasive non-typhoid Salmonella infection in children at Xiamen mainly occurred in infants younger than 3 years old.The main clinical manifestations are fever, abdominal pain and diarrhea. C-reactive protein can be served as the laboratory indicators for indicating sepsis. The third generation of cephalosporins is recommended as the first choice for treatment.
Infant ; Male ; Female ; Child ; Humans ; Child, Preschool ; Anti-Bacterial Agents/therapeutic use* ; Ceftriaxone/therapeutic use* ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use* ; Ceftazidime/therapeutic use* ; Retrospective Studies ; C-Reactive Protein ; Drug Resistance, Bacterial ; Salmonella Infections/microbiology* ; Ampicillin/therapeutic use* ; Salmonella ; Diarrhea/drug therapy* ; Bacteremia ; Abdominal Pain ; Microbial Sensitivity Tests

Objective: To investigate the risk factors for airway mucus hypersecretion in childhood pneumonia infected by different pathogens. Method: A retrospective cohort included 968 children who were hospitalized for Mycoplasma pneumoniae pneumonia (MPP), respiratory syncytial virus (RSV) pneumonia, adenovirus pneumonia and underwent bronchoscopy in Respiratory Department of Children's Hospital of Chongqing Medical University from January 2019 to December 2021 was conducted. The children were divided into two groups distinguished by airway mucus secretion according to the airway mucus hypersecretion score which were scored according to the mucus secretion under the bronchoscope. The demographic characteristics, clinical characteristics, laboratory tests and disease severity of the two groups were compared. And the risk factors for the development of airway mucus hypersecretion in two groups were analyzed. Chi square test, Mann-Whithey U test and Fisher exact test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the influencing factors. Result: There were 559 males and 409 females in the 968 children, with an age of 4.0 (1.4, 6.0) years. Among the 642 children with MPP, 185 cases were in the hypersecretion group and 457 cases were in the non-hypersecretion group. There were 41 cases in the hypersecretion group and 160 cases in the non-hypersecretion group of 201 children with RSV pneumonia. In the 125 children with adenovirus pneumonia, there were 39 cases in the hypersecretion group and 86 cases in the non-hypersecretion group. In these children, the age of children in the hypersecretion group was older than that in the non-hypersecretion group (6.0 (4.0, 7.0) vs. 5.0 (3.0, 7.0) years old, 1.5 (0.5, 3.6) vs. 0.8 (0.4, 1.6) years old, 2.0 (1.2, 4.5) vs. 1.3 (0.8, 2.0) years old, U=35 295.00, 2 492.00, 1 101.00, all P<0.05). Through multivariate Logistic regression analysis it found that increased risk of airway mucus hypersecretion was present in childhood MPP with increase in peripheral blood white blood cell count (OR=3.30, 95%CI 1.51-7.93, P=0.004) or increase in neutrophil ratio (OR=2.24, 95%CI 1.16-4.33, P=0.016) or decrease in lymphocyte count (OR=3.22, 95%CI 1.66-6.31, P<0.001) or decrease in serum albumin (OR=2.00, 95%CI 1.01-3.98, P=0.047). The risk of airway mucus hypersecretion was increased in children with RSV pneumonia combined with elevated peripheral blood eosinophils (OR=3.04, 95%CI 1.02-8.93, P=0.043). Meanwhile, airway mucus hypersecretion was associated with severe pneumonia (OR=2.46, 95%CI 1.03-6.15, P=0.047) in children with RSV pneumonia. Older age was associated with increased risk of airway mucus hypersecretion in children with adenovirus pneumonia (OR=1.02, 95%CI 1.00-1.04, P=0.026). In these children with occurrence of pulmonary rales, wheezes or sputum sounds (OR=3.65, 95%CI 1.22-12.64, P=0.028) had an increased risk of airway mucus hypersecretion. Neutrophils in bronchoalveolar lavage fluid (BALF) demonstrated higher ratio in hypersecretion group from children with MPP (0.65 (0.43, 0.81) vs. 0.59 (0.34, 0.76), U=24 507.00, P<0.01), while the proportion of macrophages in BALF was lower (0.10 (0.05, 0.20) vs. 0.12 (0.06, 0.24), U=33 043.00, P<0.05). Nucleated cell count and neutrophil ratio in BALF were higher in hypersecretion group of children with RSV pneumonia (1 210 (442, 2 100)×10⁶ vs. 490 (210, 1 510)×10⁶/L, 0.43 (0.26, 0.62) vs. 0.30 (0.13, 0.52), U=2 043.00, 2 064.00, all P<0.05). Conclusions: The increase in peripheral blood white blood cell count, neutrophil ratio and decrease in lymphocyte count, serum albumin in children with MPP is related to the development of airway mucus hypersecretion. In children with RSV pneumonia, the abnormal increase of eosinophils in peripheral blood has relationship with hypersecretion. The appearance of lung rale, wheezing, and sputum rale are associated with airway mucus hypersecretion in children with adenovirus pneumonia. In addition, local neutrophil infiltration in the respiratory tract is closely related to the occurrence of airway mucus hypersecretion caused by Mycoplasma pneumoniae and RSV infection.
Child ; Male ; Female ; Humans ; Infant ; Child, Preschool ; Retrospective Studies ; Respiratory Sounds ; Pneumonia, Mycoplasma ; Lung ; Respiratory Syncytial Virus Infections ; Mucus ; Pneumonia, Viral ; Risk Factors

ObjectiveTo investigate the value of percutaneous and intravenous contrast-enhanced ultrasound（P-Ⅳ-CEUS） in sentinel lymph nodes（SLNs） after resection of early-stage primary breast cancer. MethodsA retrospective analysis was done on the clinical and imaging data of 42 early breast cancer patients. Following primary tumor resection， all these patients underwent reoperation in our hospital. SLNs were examined by preoperative P-Ⅳ-CEUS and intraoperative sentinel lymph node biopsy（SLNB） was performed by using Methylene blue as a tracer. Then we analyzed the detection and false-negative rate in CEUS and SLNB respectively. By using the surgical pathological results as the gold standard， the diagnostic efficacy of CEUS for SLNs was explored. ResultsThe detection rate and false negative rate of SLNs in percutaneous contrast-enhanced ultrasound （P-CEUS） were 92.9% （39/42） and 7.1% （3/42）， respectively. The detection rate in methylene blue staining was 100% （41/41） and one patient underwent neoadjuvant therapy due to biopsy-confirmed metastasis. The sensitivity， specificity， positive predictive value， negative predictive value and accuracy of P-Ⅳ-CEUS were 66.7% （2/3）， 100% （37/37）， 100% （2/2）， 97.3% （36/37） and 97.4% （38/39）， respectively. ConclusionsP-Ⅳ-CEUS after resection of early-stage primary breast cancer can accurately detect SLNs and characterize their status， which is a reliable clinical basis for reducing invasive SLNB.

Abstract: Objective　To analyze the epidemiological characteristics (season, age, gender, mixed infection and clinical manifestations, etc.) of Mycoplasma pneumoniae (MP) infection in children in Hainan Province, so as to provide epidemiological evidence-based medical basis for the prevention and control of MP infection in children in Hainan Province. Methods　The serum IgM antibodies of MP, Legionella pneumophila, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus (RSV), Q fever Rickettsia, parainfluenza virus, influenza A virus and influenza B virus in children with respiratory tract infections (RTIs) who were hospitalized in pediatrics of many hospitals in Hainan Province from March 2012 to February 2020 were detected by indirect immunofluorescence method. The positive serum MP-IgM antibody was defined as MP infection. The epidemiological and clinical data of MP infected cases were analyzed retrospectively. Results　From March, 2012 to February, 2020, a total of 35 731 qualified pediatric inpatients with RTIs in many hospitals in Hainan Province were tested for serum MP-IgM with the total positive rate of 39.12% (13 978/35 731). The yearly positive rates of MP-IgM from 2012 to 2020 were 48.39%, 56.23%, 56.62%, 47.04%, 29.71%, 24.14%, 47.55%, 36.84% and 24.46% respectively. The positive rates of MP-IgM in 2013 and 2014 were significantly higher than those in other years (P<0.05). The positive rate of MP-IgM in summer in Hainan Province was the highest (41.34%) and the lowest in winter (35.77%) (P<0.05). MP infection occurred in all age groups, the positive rate of MP-IgM in children of preschool (51.80%) was significantly higher than that in other age groups (P<0.01), and the positive rate of MP IgM in children of infancy (15.36%) was lower than that in other age groups (P<0.01). The positive rate of MP-IgM in female was 44.77%, which was significantly higher than that in male (35.83%) (P<0.05). MP infection combined with positive IgM of another pathogen accounted for 32.63% (4 561 cases), positive IgM of another two pathogens accounted for 1.26% (176 cases). MP infection was mostly found in pneumonia (68.73%), and the main clinical symptoms were cough (84.72%), fever (51.01%) and wheezing (3.16%). Conclusions　MP is an important pathogen of respiratory tract infection in children in Hainan Province, and infection is more common in children in early school age and early childhood. Mp-specific tests should be performed to identify the pathogen in children suspected of MP infection. In the high incidence season, health education should be strengthened in kindergartens, schools and other places to prevent respiratory tract infection.

Objective: To understand the population structure of food-borne Staphylococcus (S.) aureus in China. Methods: Whole genome sequencing was used to analyze 763 food-borne S. aureus strains from 16 provinces in China from 2006 to 2020. Multilocus sequence typing (MLST), staphylococcal protein A gene (spa) typing, and staphylococcal chromosome cassettemec (SCCmec) typing were conducted, and minimum spanning tree based on ST types (STs) was constructed by BioNumerics 7.5 software. Thirty-one S. aureus strains isolated from imported food products were also included in constructing the genome phylogenetic tree. Results: A total of 90 STs (20 novel types) and 160 spa types were detected in the 763 S. aureus isolates. The 72 STs (72/90, 80.0%) were related to 22 clone complexes. The predominant clone complexes were CC7, CC1, CC5, CC398, CC188, CC59, CC6, CC88, CC15, and CC25, accounting for 82.44% (629/763) of the total. The STs and spa types in the predominant clone complexes changed over the years. The methicillin-resistant S. aureus (MRSA) detection rate was 7.60%, and 7 SCCmec types were identified. The ST59-t437-Ⅳa (17.24%, 10/58), ST239-t030-Ⅲ (12.07%, 7/58), ST59-t437-Ⅴb (8.62%, 5/58), ST338-t437-Ⅴb (6.90%, 4/58) and ST338-t441-Ⅴb (6.90%, 4/58) were the main types in MRSA strains. The genome phylogenetic tree had two clades, and the strains with the same CC, ST, and spa types clustered together. All CC7 methicillin sensitive S. aureus strains were included in Clade1, while 21 clone complexes and all MRSA strains were in Clade2. The MRSA strains clustered according to the SCCmec and STs. The strains from imported food products in CC398, CC7, CC30, CC12, and CC188 had far distances from Chinese strains in the tree. Conclusions: In this study, the predominant clone complexes of food-borne strains were CC7, CC1, CC5, CC398, CC188, CC59, CC6, CC88, CC15, and CC25, which overlapped with the previously reported clone complexes of hospital and community-associated strains in China, suggesting that close attention needs to be paid to food, a vehicle of pathogen transmission in community and food poisoning.
Humans ; Staphylococcus aureus/genetics* ; Methicillin-Resistant Staphylococcus aureus/genetics* ; Multilocus Sequence Typing ; Phylogeny ; Staphylococcal Infections/epidemiology* ; China/epidemiology*

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Aim To research the effect of gender on immune function and keratinocyte damage in imiquimod(IMQ)induced psoriasis mice.Methods IMQ-induced psoriasis mice were freely divided into female and male model groups, and female and male normal groups were set up smeared with an equal amount of petroleum.PASI score and HE staining were used to evaluate skin lesion and pathology; Western blot and immunity fluorescence were used to detect the expression of proliferating cell nuclear antigen(PCNA), Ki67, keratin 1(K1), keratin 10(K10), and involucrin in skin lesions; spleen index of mice was calculated; immunohistochemistry was used to detect the expression of CD4, IFN-γ, IL-4, and IL-17 in skin and spleen; flow cytometry was used to detect the changes of Th1 and Th17 cell subsets in spleen.Results Compared with female and male normal groups, PASI score of female and male model groups increased, skin lesions were abnormally thickened and differentiated, the level of PCNA and Ki67, the spleen index, the Th1 and Th17 cell subsets in the spleen both increased, K1, K10, and involucrin decreased, the levels of CD4, IFN-γ, IL-17 in skin lesions and spleen were elevated, but the level of IL-4 showed the opposite trend.There was no statistical difference in the above indicators between the female and male model groups.Conclusion Gender has no effect on the abnormal activation of T cell immune function and the proliferation and differentiation of keratinocytes in psoriasis-like mice induced by IMQ.

To analyze the mechanism of novel coronavirus prevention prescription in Hunan province by using network pharmacology method. Methods TCMSP, Batman-TCM and ETCM were used to retrieve drug composition and target information, and GeneCards, OMIM, DrugBank, TTD and PharmGkb were used to screen disease targets. The visualization network diagram of "drug-active component-target" was constructed by Cytoscape, the protein interaction network was drawn by STRING, the core targets of PPI network were analyzed by CytoNCA, GO function and KEGG pathway were analyzed, and the mechanism of action was predicted. Results A total of 418 active ingredients, 1 715 drug targets, 1 289 disease targets and 266 intersection targets were screened out. Quercetin, luteolin, kaempferol, baicalein, ursolic acid and naringin were identified as the key components, and 6 core targets were obtained: RELA, AKT1, STAT3, JUN, MAPK1 and MAPK3. The results of molecular docking showed that the binding potential and activity of the key active ingredients to the core target were good. Conclusions "Child prevention formula" has the characteristics of multi-target, multi-approach and multi-faceted prevention and treatment, which plays a role in prevention and treatment of COVID-19 among children.