Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by congenital bilateral malformation of the large toe and progressive, extensive, and irreversible heterotopic ossification (HO) of soft tissues throughout the body, leading to severe disabilities. FOP is caused primarily by mutations in activin A receptor type 1 (ACVR1), also known as activin-like kinase 2 (ALK2), which encodes a receptor belonging to the bone morphogenetic protein (BMP) type I family. However, the continuous and complex process of HO in FOP is not yet fully understood, which has impeded the development of therapeutic drugs. Despite surgical removal of HO, which often results in recurrence and expansion of ossification, there is currently no definitive drug treatment available to completely prevent, halt, or reverse the progression of HO in FOP. Currently, researchers are intensively studying the pathogenesis of FOP at various stages and developing promising drug candidates, including saracatinib, palovarotene, and rapamycin. This review provides an overview of progress in understanding the mechanism of FOP and the development of therapeutic drugs, with the goal of providing insights for further research and the development of new treatment methods.
Myositis Ossificans/genetics* ; Humans ; Activin Receptors, Type I/genetics* ; Ossification, Heterotopic ; Mutation ; Sirolimus/therapeutic use* ; Quinolones/therapeutic use* ; Benzodioxoles/therapeutic use* ; Animals ; Quinazolines/therapeutic use*

Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Killer Cells, Natural/metabolism* ; Exosomes/metabolism* ; Animals ; Humans ; Otitis Media/therapy* ; Staphylococcus aureus/drug effects* ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology* ; Levofloxacin/pharmacology*

Objective: This paper demonstrated the effectiveness of intrastromal injection of levofloxacin 1.5% ophthalmic solution in the management of recalcitrant Gram-positive bacterial keratitis. Methods: This is a report on two cases of recalcitrant bacterial keratitis encountered at the External Diseases and Cornea Clinic of the Department of Ophthalmology and Visual Sciences at the Philippine General Hospital. Results: Two middle-aged females presented with bacterial keratitis unresponsive to previous antibiotic treatment with impending corneal perforation. The Gram stain of the corneal scraping in the first case revealed Gram-positive cocci, while the second case showed encapsulated Gram-positive bacilli and encapsulated Grampositive cocci in chains. In both cases, repeated intrastromal injections of levofloxacin 1.5% in addition to increasing the frequency of topical levofloxacin 1.5% resulted in marked improvement in visual acuity and resolution of deep stromal infiltrates and hypopyon. Conclusion These cases highlighted the utility of intrastromal levofloxacin 1.5% ophthalmic solution in the management of recalcitrant Gram-positive bacterial keratitis.
Fluoroquinolones ; Levofloxacin

OBJECTIVE: To investigate the clinical efficacy of Huang'e Capsules in the treatment of type ⅢA chronic prostatitis, and its effects on the levels of the inflammatory cytokines neutrophil elastase (NE), IL-8 and TGF-β1 in the expressed prostatic secretion (EPS) of the patients. METHODS: We selected 120 patients with type ⅢA chronic prostatitis and randomly assigned them to medication with Huang'e Capsules (the trial group, n = 60) or Levofloxacin and Tamsulosin (the control group, n = 60), both for a course of 4 weeks. We obtained the NIH-CPSI scores and the levels of NE, IL-8 and TGF-β1 in the EPS, and compared them between the two groups before and after treatment. RESULTS: Totally, 116 of the patients completed the study, 59 in the trial and 57 in the control group. The overall clinical effectiveness was significantly higher in the trial group than in the control (89.8% vs 77.2%, P<0.05). Compared with the baseline, the patients of the trial group showed significant decreases after treatment in the total NIH-CPSI scores (32.5±7.4 vs 13.2±5.1), pain symptom scores (13.7±3.9 vs 4.2±2.3), urination symptom scores (6.9±2.4 vs 5.1±3.2) and quality of life (QOL) scores (8.3±2.7 vs 3.7±1.5) (all P< 0.05), and so did the controls in the total NIH-CPSI scores (30.8±7.8 vs 13.7±3.9), pain symptom scores (14.2±4.1 vs 7.8±2.9), urination symptom scores (7.1±2.7 vs 4.9±3.4) and quality of life (QOL) scores (8.1±2.4 vs 5.6±1.9) (all P< 0.05), and the decreases were even more significant in the trial than in the control group in the pain symptom and QOL scores ( P< 0.05). The patients of the trial group also exhibited a marked reduction after treatment in the contents of NE (［1135.4±321.5］ vs ［347.6±207.3］ ng/L, P< 0.05) and IL-8 (［974.9±231.6］ vs ［ 431.3±207.2］ ng/L, P< 0.05) but an elevation in that of TGF-β1 (［591.0±172.1］ vs ［1 402.1 ± 221.5］ ng/L, P< 0.05) in the EPS, and so did the controls in the levels of NE (［1052.8±280.3］ vs ［761.1±225.1］ ng/L, P<0.05), (［1007.5±287.7］ vs ［775.7±182.5］ ng/L, P< 0.05), (［607.8±201.3］ vs ［871.3±192.5］ ng/L, P< 0.05), with even more significant improvement in the trial than in the control group (P< 0.05). CONCLUSION Huang'e Capsules has a significant clinical efficacy and safety in the treatment of type IIIA prostatitis, which can effectively relieve the pain and urination symptoms and improve the levels of the inflammatory cytokines NE, IL-8 and TGF-β1 in the patients.
Humans ; Male ; Prostatitis/metabolism* ; Interleukin-8/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Transforming Growth Factor beta1/metabolism* ; Prostate/metabolism* ; Leukocyte Elastase/metabolism* ; Tamsulosin ; Treatment Outcome ; Capsules ; Middle Aged ; Phytotherapy ; Cytokines/metabolism* ; Adult ; Levofloxacin

OBJECTIVE: To analyze the distribution and drug resistance of pathogens in oral mucositis associated with chemotherapy in hospitalized patients with malignant hematopathy, so as to provide scientific evidences for rational selection of antibiotics and infection prevention and control. METHODS: From July 2020 to June 2022, 167 patients with malignant hematopathy were treated with chemical drugs in the Department of Hematology, Hainan Hospital, and secretions from oral mucosal infected wounds were collected. VITEK2 COMPECT automatic microbial identification system (BioMerieux, France) and bacterial susceptibility card (BioMerieux) were used for bacterial identification and drug susceptibility tests. RESULTS: A total of 352 strains of pathogens were isolated from 167 patients, among which 220 strains of Gram-positive bacteria, 118 strains of Gram-negative bacteria and 14 strains of fungi, accounted for 62.50%, 33.52% and 3.98%, respectively. The Gram-positive bacteria was mainly Staphylococcus and Streptococcus, while Gram-negative bacteria was mainly Klebsiella and Proteus. The resistance of main Gram-positive bacteria to vancomycin, ciprofloxacin and gentamicin was low, and the resistance to penicillin, cefuroxime, ampicillin, cefotaxime, erythromycin and levofloxacin was high. The main Gram-negative bacteria had low resistance to gentamicin, imipenem and penicillin, but high resistance to levofloxacin, cefotaxime, cefuroxime, ampicillin and vancomycin. The clinical data of oral mucositis patients with oral ulcer (severe) and without oral ulcer (mild) were compared, and it was found that there were statistically significant differences in poor oral hygiene, diabetes, sleep duration less than 8 hours per night between two groups (P<0.05). CONCLUSION Gram-positive bacteria is the main pathogen of oral mucositis in patients with malignant hematopathy after chemotherapy. It is sensitive to glycopeptide antibiotics and aminoglycosides antibiotics. Poor oral hygiene, diabetes and sleep duration less than 8 hours per night are risk factors for oral mucositis with oral ulcer (severe).
Humans ; Vancomycin/therapeutic use* ; Cefuroxime ; Levofloxacin ; Oral Ulcer/drug therapy* ; Drug Resistance, Bacterial ; Anti-Bacterial Agents/adverse effects* ; Ampicillin ; Penicillins ; Cefotaxime ; Gram-Positive Bacteria ; Gram-Negative Bacteria ; Gentamicins ; Stomatitis/drug therapy*

OBJECTIVE: To investigate the inhibitory effects of levofloxacin (LEV) combined with cellulase against bacille CalmetteGuerin (BCG) biofilms in vitro. METHODS: The mature growth cycle of BCG biofilms was determined using the XTT method and crystal violet staining. BCG planktonic bacteria and BCG biofilms were treated with different concentrations of LEV and cellulose alone or jointly, and the changes in biofilm biomass were quantified with crystal violet staining. The mature BCG biofilm was then treated with cellulase alone for 24 h, and after staining with SYTO 9 and Calcofluor White Stain, the number of viable bacteria and the change in cellulose content in the biofilm were observed with confocal laser scanning microscopy. The structural changes of the treated biofilm were observed under scanning electron microscopy. RESULTS: The MIC, MBC and MBEC values of LEV determined by broth microdilution method were 4 μg/mL, 8 μg/mL and 1024 μg/mL, respectively. The combined treatment with 1/4×MIC LEV and 2.56, 5.12 or 10.24 U/mL cellulase resulted in a significant reduction in biofilm biomass (P < 0.001). Cellulase treatments at the concentrations of 10.24, 5.12 and 2.56 U/mL all produced significant dispersion effects on mature BCG biofilms (P < 0.001). CONCLUSION LEV combined with cellulose can effectively eradicate BCG biofilm infections, suggesting the potential of glycoside hydrolase therapy for improving the efficacy of antibiotics against biofilmassociated infections caused by Mycobacterium tuberculosis.
Levofloxacin/pharmacology* ; Gentian Violet/pharmacology* ; BCG Vaccine/pharmacology* ; Anti-Bacterial Agents/pharmacology* ; Biofilms ; Cellulases/pharmacology* ; Microbial Sensitivity Tests

Humans ; Mycobacterium tuberculosis/genetics* ; Microspheres ; Antitubercular Agents/pharmacology* ; Mutation ; Microbial Sensitivity Tests ; Fluoroquinolones ; Drug Resistance, Bacterial/genetics* ; Tuberculosis, Multidrug-Resistant/microbiology*

Humans ; Aripiprazole/therapeutic use* ; Schizophrenia/drug therapy* ; Antipsychotic Agents/therapeutic use* ; Risperidone ; China ; Treatment Outcome

Objective: To explore the clinical characteristics, common pathogens in children with vulvovaginitis. Methods: This was a retrospective cases study. A total of 3 268 children with vulvovaginitis were enrolled, who visited the Department of Pediatric and Adolescent Gynecology, Children's Hospital, Zhejiang University School of Medicine from January 2009 to December 2019. Patients were divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Patients were also divided in to 4 groups according to the season of first visit. The pathogen distribution characteristics of infective vulvovaginitis were compared between the groups. Their clinical data were collected and then analyzed by χ² test. Results: The were 3 268 girls aged (6.2±2.5) years. There were 1 728 cases (52.9%) aged <7 years, 875 cases (26.8%) aged 7-<10 years, and 665 cases (20.3%) aged 10-18 years. Of these cases, 2 253 cases (68.9%) were bacterial vulvovaginitis, 715 cases (21.9%) were fungal vulvovaginitis and 300 cases (9.2%) were vulvovaginitis infected with other pathogens. Bacterial culture of vaginal secretions was performed in 2 287 cases, and 2 287 strains (70.0%) of pathogens were detected, of which the top 5 pathogens were Streptococcus pyogenes (745 strains, 32.6%), Haemophilus influenzae (717 strains, 31.4%), Escherichia coli (292 strains, 12.8%), Staphylococcus aureus (222 strains, 9.7%) and Klebsiella pneumoniae (67 strains, 2.9%). Regarding different age groups, H.influenzae was the most common in children under 7 years of age (40.3%, 509/1 263), S.pyogenes (41.9%, 356/849) was predominantly in children aged 7 to 10 years, and E.coli was predominant in children aged 10 to 18 years (26.3%, 46/175). Susceptibility results showed that S.pyogenes was susceptible to penicillin G (610/610, 100.0%), ceftriaxone (525/525, 100.0%), and vancomycin (610/610, 100.0%); the resistance rates to erythromycin and clindamycin were 91.9% (501/545)and 90.7% (495/546), respectively. For H.influenzae, 32.5% (161/496) produced β-elactamase, and all strains were sensitive to meropenem (489/489, 100.0%) and levofloxacin (388/388, 100.0%), while 40.5% (202/499) were resistant to ampicillin. Among E.coli, all strains were sensitive to imipenem(100%, 175/175). The resistance rates of E.coli to levofloxacin and ceftriaxone were 29.1% (43/148) and 35.1% (59/168), respectively. A total of 48 strains of methicillin-resistant Staphylococcus aureus (MRSA) were isolated with a proportion of 28.3% (45/159) in 3 268 patients. The results of drug susceptibility test showed that all MRSA strains were sensitive to linezolid 100.0% (40/40), vancomycin (45/45, 100.0%), and tigecycline (36/36, 100.0%); the resistance rates of MRSA to penicillin G, erythromycin and clindamycin were 100% (45/45), 95.6% (43/45) and 88.9% (40/45), respectively. All methicillin-sensitive Staphylococcus aureus (MSSA) strains were sensitive to oxacillin (114/114, 100.0%), linezolid (94/94, 100.0%), vancomycin (114/114, 100.0%), and tigecycline (84/84, 100.0%); it's resistance rates to penicillin G, erythromycin and clindamycin were 78.1% (89/114), 59.7% (68/114) and 46.5% (53/114), respectively. The drug resistance rate of MSSA to penicillin G, erythromycin and clindamycin were lower than those of MRSA (χ²=11.71,19.74,23.95, respectively, all P<0.001). Conclusions: The age of consultation for pediatric infectious vulvovaginitis is mainly around 6 years. The most common pathogens are S.pyogenes, H.influenzae and Escherichia coli. Third generation cephalosporins can be used as the first choice of empirical anti-infection drugs. However, the results of drug susceptibility should be considered for targeted treatment.
Female ; Adolescent ; Child ; Humans ; Anti-Bacterial Agents/therapeutic use* ; Vancomycin/therapeutic use* ; Methicillin-Resistant Staphylococcus aureus ; Clindamycin/therapeutic use* ; Ceftriaxone/therapeutic use* ; Tigecycline/therapeutic use* ; Linezolid/therapeutic use* ; Levofloxacin/therapeutic use* ; Retrospective Studies ; Microbial Sensitivity Tests ; Staphylococcus aureus ; Staphylococcal Infections/drug therapy* ; Erythromycin/therapeutic use* ; Methicillin ; Penicillin G/therapeutic use* ; Escherichia coli ; Drug Resistance, Bacterial

Antitubercular Agents/therapeutic use* ; China/epidemiology* ; Drug Resistance, Multiple, Bacterial ; Extensively Drug-Resistant Tuberculosis ; Humans ; Kanamycin Resistance ; Microbial Sensitivity Tests ; Mycobacterium tuberculosis ; Ofloxacin/pharmacology* ; Tuberculosis, Multidrug-Resistant/epidemiology*