Role of Dectin-1 in immune response of macrophages induced by Fonsecaea monophora wild strain and melanin-deficient mutant strain.

Chromoblastomycosis is a chronic granulomatous subcutaneous fungal disease caused mainly by Fonsecaea monophora in southern China. Melanin is an important virulence factor in wild strain (Mel+), and the strains lack of the polyketide synthase gene is a melanin-deficient mutant strain (Mel-). We investigated the effect of melanin in F. monophora on Dectin-1 receptor-mediated immune responses in macrophages. Conidia and tiny hyphae of Mel+ and Mel- were co-cultured with THP-1 macrophages expressing normal or low levels of Dectin-1. Compare the killing rate, phagocytosis rate, and expression levels of the inflammatory cytokines tumour necrosis factor-α, interleukin-1ß, interleukin-6, and nitric oxide in each group. The results showed that the killing rate, phagocytosis rate, and pro-inflammatory factor levels of Mel+ infected macrophages with normal expression of Dectin-1 were lower than those of Mel-. And the knockdown of Dectin-1 inhibited the phagocytic rate, killing rate, and proinflammatory factor expression in macrophages infected with Mel+ and Mel-. And there was no significant difference in the above indexes between Mel+ and Mel- groups in Dectin-1 knockdown macrophages. In summary, the study reveals that melanin of F. monophora inhibits the immune response effect of the host by hindering its binding to Dectin-1 on the surface of macrophage, which may lead to persistent fungal infections.

Evaluating the efficacy of different antibiotics against Neisseria gonorrhoeae: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

BACKGROUND: With the widespread use of antibiotics, antimicrobial resistance in Neisseria gonorrhoeae is worsening. The objective of this study was to evaluate the efficacy changes of seven antibiotics in the treatment of N. gonorrhoeae by using Monte Carlo simulation combined with pharmacokinetics/pharmacodynamics/ (PK/PD). METHODS: The minimum inhibitory concentration (MIC) of antibiotics against clinical isolates from 2013 to 2020 in Nanjing, China, was determined by agar dilution method. The probability of target attainment (PTA) was estimated at each MIC value and the cumulative fraction of response (CFR) was calculated to evaluate the efficacy of these regimens. RESULTS: All dosage regimens of seven antibiotics achieved PTAs ≥ 90% for MIC ≤ 0.06 µg/ml. But when the MIC was increased to 1 µg/ml, PTAs at each MIC value exceeded 90% only for ceftriaxone 1,000 mg and 2,000 mg, zoliflodacin 2,000 mg and 3,000 mg. Among them, the CFR values of each dosing regimen against N. gonorrhoeae only for ceftriaxone, cefixime and zoliflodacin were ≥ 90% in Nanjing from 2013 to 2020. CONCLUSIONS: Cephalosporins are still the first-line drugs in the treatment of gonorrhea. However, the elevated MIC values of cephalosporins can lead to decline in clinical efficacy of the conventional dose regimens, and increasing the dose of ceftriaxone to 1,000 mg-2,000 mg may improve the efficacy. In addition, zoliflodacin is possible to be a potential therapeutic agent in the future.

Effects of diaphragm electrical stimulation in treating respiratory dysfunction on mechanical ventilation after intracerebral hemorrhage: A single-center retrospective study.

Intracerebral hemorrhage (ICH) is a major cause of death and disability worldwide. The benefits of electrical stimulation in the treatment of respiratory dysfunction in patients on mechanical ventilation is unknown. Nevertheless, there is a dearth of evidence-based medical research concerning its clinical efficacy. From January 2019 to January 2023, every enrolled patients experienced respiratory dysfunction after ICH while being supported by mechanical ventilation. A total of 205 eligible patients were enrolled and then allocated into 2 groups: control group and observation group. 133 patients was selected and administered standard treatment as control group. Based on conventional treatment, other 72 patients were administered diaphragm electrical stimulation (DES) treatment. We examined information from current medical records, encompassing all initial data and predictive follow-up data, such as the weaning success rate, occurrence of ventilator-associated pneumonia (VAP), duration of stay in the intensive care unit (ICU) and hospital, expenses related to hospitalization, and mortality within 30 days. The baseline clinical data of the 2 groups did not exhibit any statistically significant disparities (all P > .05). The rate of successful weaning showed a significant increase in the DES group when compared to the control group (P = .025). In patients with respiratory dysfunction due to ICH, treatment with DES resulted in a significant reduction in the duration of invasive ventilation (9.8 ±â€…2.1 vs 11.2 ±â€…2.6, P < .01) and total ventilation time (9.8 ±â€…2.1 vs 11.2 ±â€…2.6, P < .01). It also led to a decrease in the length of stay in the ICU (15.67 ±â€…3.76 vs 17.53 ±â€…4.28, P = .002) and hospitalization cost (11500 vs 13600, P = .001). Additionally, DES treatment resulted in a lower incidence of VAP (73.61% vs 86.46%, P = .022) and improved 30-day mortality (P < .05), without any significant adverse effects. The findings of this research indicate that DESs have a positive impact on enhancing the rate of successful weaning and reducing the incidence of VAP. It decreases the duration of invasive ventilation and total ventilation time while also improving the mortality rate within 30 days. This therapy could offer a fresh alternative for respiratory impairment in patients undergoing mechanical ventilation.

5-aminolevulinic acid-based photodynamic therapy in combination with antifungal agents for adult kerion and facial ulcer caused by Trichophyton rubrum.

Dermatophytosis is the most common fungal infectious disease in the world, which is commonly caused by Trichophyton rubrum in China. The traditional therapies for treating dermatophytosis include topical and oral antifungal agents like terbinafine, griseofulvin, and azole antifungal drugs. However, 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) as a new alternative therapy avoids the side effects and drug resistance of traditional antifungal agents. We report two cases diagnosed as kerion and tinea faciei secondary to ulcers with CARD 9 deficiency, both of whom were infected by T.rubrum. They were both successfully treated by ALA-PDT combined with antifungal drugs, providing a feasible strategy for therapeutic choice for adult kerion and ulcer treatment.

Clinical Characteristics Predict Recurrence in Borderline Ovarian Tumor Patients with Fertility-Preserving Surgery.

PURPOSE: To identify prognostic factors in patients with borderline ovarian tumor (BOT) and establish and validate a nomogram predicting recurrence in BOT patients treated with fertility-preserving surgery. PATIENTS AND METHODS: Patients with BOT who underwent surgery at two institutions between January 2000 and June 2017 were included and categorized into training and validation cohorts. Univariate log rank test and Cox regression analysis were performed in the training cohort to identify prognostic factors, and a nomogram was developed to predict the recurrence rate. The model was validated by calculating the C-index and drawing the calibration curve and receiver operating curve (ROC). CONCLUSION: In the multivariate Cox regression analysis, practice period, past history of benign ovarian disease, past history of benign breast disease, elevated CA125 levels, elevated CA199 levels, surgical methods, greater omentum resection, FIGO stage, postoperative pregnancy, and re-operation were independently associated with recurrence-free survival (p<0.05). The aforementioned prognostic factors were used to develop a nomogram. The nomogram demonstrated a good ability to predict the risk of recurrence (training cohort C-index: 0.866, validation cohort C-index: 0.920). The calibration curve suggested that the predicted recurrence-free survival was closely related to the actual recurrence. ROC analysis showed that the nomogram had a good discriminatory power with the area under curve between 0.776 and 0.956. The nomogram can predict the 1-, 3-, and 5-year recurrence-free survival of BOT patients undergoing fertility-preserving surgery. The predictive model can help guide surgical plans, postoperative monitoring, and prognostic evaluation of BOT patients.

Development and validation of a nomogram risk prediction model for malignancy in dermatomyositis patients: a retrospective study.

BACKGROUND: Dermatomyositis accompanied with malignancy is a common poor prognostic factor of dermatomyositis. Thus, the early prediction of the risk of malignancy in patients with dermatomyositis can significantly improve the prognosis of patients. However, the identification of antibodies related to malignancy in dermatomyositis patients has not been widely implemented in clinical practice. Herein, we established a predictive nomogram model for the diagnosis of dermatomyositis associated with malignancy. METHODS: We retrospectively analyzed 240 cases of dermatomyositis patients admitted to Sun Yat-sen Memorial Hospital, Sun Yat-sen University from January 2002 to December 2019. According to the year of admission, the first 70% of the patients were used to establish a training cohort, and the remaining 30% were assigned to the validation cohort. Univariate analysis was performed on all variables, and statistically relevant variables were further included in a multivariate logistic regression analysis to screen for independent predictors. Finally, a nomogram was constructed based on these independent predictors. Bootstrap repeated sampling calculation C-index was used to evaluate the model's calibration, and area under the curve (AUC) was used to evaluate the model discrimination ability. RESULTS: Multivariate logistic analysis showed that patients older than 50-year-old, dysphagia, refractory itching, and elevated creatine kinase were independent risk factors for dermatomyositis associated with malignancy, while interstitial lung disease was a protective factor. Based on this, we constructed a nomogram using the above-mentioned five factors. The C-index was 0.780 (95% CI [0.690-0.870]) in the training cohort and 0.756 (95% CI [0.618-0.893]) in the validation cohort, while the AUC value was 0.756 (95% CI [0.600-0.833]). Taken together, our nomogram showed good calibration and was effective in predicting which dermatomyositis patients were at a higher risk of developing malignant tumors.

Identification of significant genes signatures and prognostic biomarkers in cervical squamous carcinoma via bioinformatic data.

BACKGROUND: Cervical squamous cancer (CESC) is an intractable gynecological malignancy because of its high mortality rate and difficulty in early diagnosis. Several biomarkers have been found to predict the prognose of CESC using bioinformatics methods, but they still lack clinical effectiveness. Most of the existing bioinformatic studies only focus on the changes of oncogenes but neglect the differences on the protein level and molecular biology validation are rarely conducted. METHODS: Gene set data from the NCBI-GEO database were used in this study to compare the differences of gene and protein levels between normal and cancer tissues through significant pathway selection and core gene signature analysis to screen potential clinical biomarkers of CESC. Subsequently, the molecular and protein levels of clinical samples were verified by quantitative transcription PCR, western blot and immunohistochemistry. RESULTS: Three differentially expressed genes (RFC4, MCM2, TOP2A) were found to have a significant survival (P < 0.05) and highly expressed in CESC tissues. Molecular biological verification using quantitative reverse transcribed PCR, western blotting and immunohistochemistry assays exhibited significant differences in the expression of RFC4 between CESC and para-cancerous tissues (P < 0.05). CONCLUSION: This study identified three potential biomarkers (RFC4, MCM2, TOP2A) of CESC which may be useful to clarify the underlying mechanisms of CESC and predict the prognosis of CESC patients.

[Responses of potential suitable area of Paris verticillata to climate change and its dominant climate factors]. / åŒ—é‡æ¥¼æ½œåœ¨é€‚ç”ŸåŒºå¯¹æ°”å€™å˜åŒ–çš„å“åº”åŠå ¶ä¸»å¯¼æ°”å€™å› å­.

Prediction of the potential distribution of species based on the data of its current distribution in combination with climatic variables is important for understanding species evolution and reasonable conservation. Based on 220 distribution sites in China and 12 low-correlation climatic variables, we analyzed the potential distribution of Paris verticillata at present and future (2050s and 2070s) using the MaxEnt model and ArcGIS program. Further, we analyzed the dominant driving factors for its geographic distribution. The results showed that the area under the curve indices (AUC) was 0.940, with high prediction accuracy. The potential suitable regions of P. verticillata were mainly distributed in the Greater Xing'an Mountains, the Xiao Xing'an Mountains, the Changbai Mountains, the Qinling-Daba Mountains, Hebei, Shanxi and north Shandong under current climate scenario. Those regions accounted for 18.1% of the total suitable area in the country, of which the highly suitable areas accounted for 7.0% and the lowly suitable area 11.1%. The total suitable areas of P. verticillata in the 2050s and 2070s would decline under the climate change scenarios of RCP 2.6, RCP 4.5, RCP 6.0 and RCP 8.5. The highly suitable area would decline, but the lowly suitable area would increase. With the global climate change, both the range and the geometric center of its distribution would gradually spread to higher altitude in the northeast. The cumulative contributions of four dominant factors reached as high as 89.2%, namely, precipitation of wettest month, mean annual temperature, isothermality, and precipitation of January. Their appropriate ranges were 100-275 mm, -0.1-16 ℃, 21-35 and 3-14 mm, respectively.

Four Surgical Strategies for the Treatment of Cesarean Scar Defect: A Systematic Review and Network Meta-analysis.

OBJECTIVE: This network meta-analysis compared treatment via laparoscopy, hysteroscopy (HP), combined laparoscopy with HP (LH), and vaginal repair (VR) for reducing intermittent abnormal uterine bleeding and cesarean scar defect (CSD) diverticulum depth in patients with CSD. DATA SOURCES: Electronic databases (PubMed, EMBASE, The Cochrane Central Register of Controlled Trials, MEDLINE, ClinicalTrials.gov, Chinese Biomedical Literature Database, and China National Knowledge Integrated) were searched for articles published through June 13, 2018. METHODS OF STUDY SELECTION: The search included randomized controlled trials (RCTs) and observational studies of surgical treatment for CSD. Standardized mean difference (SMD) and 95% confidence intervals (CIs) were reported. RCTs were evaluated by the Cochrane risk-of-bias tool, observational studies by Risk of Bias in Nonrandomized Studies of Intervention, and overall evidence quality by grade. Data were analyzed by STATA (version 15.0; StataCorp, College Station, TX) and R software for windows (version 3.5.0; R Core Team, 2018). TABULATION, INTEGRATION, AND RESULTS: Ten studies (n = 858; 4 RCTs and 6 observational studies) were included. Patients who underwent uterine diverticulum resection by LH had a shorter duration of abnormal uterine bleeding than those by HP (SMD = 1.36, 95% CI, 0.37-2.36; p = .007) and VR (SMD = 1.58, 95% CI, 0.97-2.19; p <.0001). LH reduced the CSD diverticulum depth more than VR (SMD = 1.57, 95% CI, 0.54-2.61; p = .003). There was no significant difference in efficacy among the surgical procedures. CONCLUSION: LH reduced intermittent abnormal uterine bleeding and scar depth more than the other surgical interventions. Larger clinical trials are warranted to verify this analysis.

Botulinum Toxin A Injection for Treatment of Chronic Skin Ulcer: A Case Series and Literature Review.

Chronic skin ulcer (CSU) often combines with a variety of refractory factors that respond poorly to routine treatments. Botulinum toxin A (BTX-A) can be injected subcutaneously to improve the local blood supply, to reduce pain, and to promote wound healing. At present, few reports have mentioned BTX-A injection for chronic skin ulcer treatment. We observed the effect of four cases that used BTX-A to treat CSU and provided a brief review of the literature. Four cases of CSUs with 4 different causes were treated with BTX-A injection (4 U/cm2). The specific operation is as follows: local, multipoint, cyclic, equidistant, and subcutaneous injections with a depth of 6 to 8 mm. The ulcer area was significantly reduced. Subsequently, the ulcer healed within 20 to 48 days. Botulinum toxin A is recommended as an important treatment for chronic skin ulcer that can improve healing of skin ulcers with various etiologies.