Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.

ObjectiveTo review the drug information and research progress on oral Chinese patent medicines in the treatment of cardiac arrhythmia to identify existing problems and provide references for follow-up research. MethodChinese patent medicines against cardiac arrhythmia were retrieved from the three major drug catalogues，Yaozh.com，and relevant guidelines with arrhythmia as the retrieval term. The instructions for included Chinese patent medicines were retrieved through Yaozh.com and specific information was extracted. The research articles on Chinese patent medicines included were retrieved from the five databases，and the information meeting the inclusion and exclusion criteria was extracted and displayed in the form of text description and graphs after statistical analysis. ResultSixty-five oral Chinese patent medicines were included in this study，with the main functions of activating the blood and resolving stasis. The average daily cost of medicines was 8.17 yuan，and there were 42 medicines with an average daily cost of less than 10 yuan，showing a moderate medicine cost. A total of 351 research articles on Chinese patent medicines were screened out，including 259 randomized controlled trials （RCTs），16 non-RCTs，eight non-controlled trials，62 systematic reviews，two guidelines，and two expert consensuses. Eighteen types of Chinese patent medicines were involved，whose clinical trials had been conducted in 28 provinces，cities，autonomous regions，and municipalities in China. Wenxin granules and Shensong Yangxin capsules were the top medicines under investigation，accounting for 75.21% of all research articles. Among the included studies，the most common comparison design was Chinese patent medicine combined with western medicine vs western medicine （64.25%）. The outcome evaluation was mainly based on clinical efficacy，symptom efficacy，arrhythmia efficacy，adverse reactions，and heart rate changes. ConclusionThe number of clinical studies of oral Chinese patent medicines against cardiac arrhythmia varies greatly，but traditional Chinese medicine （TCM） syndrome differentiation thinking is less considered in practical application. Due to unstandardized clinical research and low-quality literature，further advancement is required in the future.

ObjectiveTo analyze the microbial diversity in the rhizosphere soil of Gastrodia elata with different yields and explore the influence of soil microorganisms on the yield of G. elata. MethodThe experiment adopted the 16S DNA and ITS high-throughput sequencing technologies to study the diversity of the bacterial and fungal community in the rhizosphere soil of G. elata with high yield （GC） and low yield （DC）. ResultProteobacteria， Firmicutes， and other unidentified Bacteria were dominant in the rhizosphere soil of G. elata. The dominant rhizosphere fungi were Ascomycota， Basidiomycota， and Mortierellomycota. There was no significant difference in microbial community abundance in the high-yield and low-yield rhizosphere soil of G. elata， but there was a significant difference in species composition. Thirty-eight microbes such as Bradyrhizobium， Schleiferilactobacillus， and Archaeorhizomyces were gathered in large numbers in the high-yield rhizosphere soil， and thirty microbes such as Fusarium， Coprinellus， and Nitrosotalea were gathered in large numbers in the low-yield rhizosphere soil. At the level of genus and species， there were six different species in the high-yield and low-yield rhizosphere soil of G. elata， among which Russula mariae， Archeaeorhizomyces， and Ilyonectria were gathered in the high-yield rhizosphere soil of G. elata， while Nitrosotalea， Coprinellus disserminatus， and Fusarium were gathered in the low-yield rhizosphere soil of G. elata. ConclusionThere are different microorganisms in the rhizosphere soil of G. elata with different yields， and it is speculated that these microorganisms are related to the yields of G. elata. The research results are expected to provide a vital theoretical basis for the follow-up study of the high yield of G. elata.

Objective: Depression was common during coronavirus disease-2019 (COVID-19) pandemic, while the association of perceived stress with depression among vaccinated healthcare workers has not been investigated. This study aimed to address this issue. Methods: We included a total of 898 fully vaccinated healthcare workers during the outbreak of severe acute respiratory syndrome coronavirus 2 Delta variant in Nanjing, 2021. Depression was ascertained by Patient Health Questionnaire-9, with a cut-off score of ≥5 indicative of mild-to-severe depression. Perceived stress, resilience, and compassion fatigue were assessed by Perceived Stress Scale-10, Resilience Scale-25, and Professional Quality of Life Scale version-5, respectively. Logistic regression analyses were used to estimate the odds ratio (OR) and 95% confidence interval (CI), along with subgroup and mediation analyses. Results: The prevalence of mild-to-severe depression was 41.1% in vaccinated healthcare workers. The odd of mild-to-severe depression was increased with higher perceived stress. Compared with vaccinated healthcare workers with the lowest tertile of perceived stress, those with the highest tertile had increased odds of mild-to-severe depression by 120% (OR 2.20, 95% CI 1.46 to 3.31) after multivariable-adjustment. However, perceived stress was not associated with mild-to-severe depression in vaccinated healthcare workers with strong resilience, but was in those with weak resilience (pinteraction=0.004). Further analysis showed that compassion fatigue mediated the relationship between perceived stress and mild-to-severe depression, with a mediating effect of 49.7%. Conclusion Perceived stress was related to an increased odd of mild-to-severe depression in vaccinated healthcare workers during COVID-19 pandemic, and this relationship might be explained by compassion fatigue.

Objective:To investigate the distribution and antimicrobial resistance patterns of common pathogens in children with urinary tract infections in a single center in Shanghai, and to provide basis for the selection of empirical antibiotics in the clinical practice.Methods:The clinical data, urine culture and drug sensitivity tests results of children with urinary tract infections between 0 to 14 years admitted to the Children′s Hospital of Fudan University from January 2016 to December 2019 were retrospectively analyzed. According to the time of onset and the complicated factors, the patients were divided into different groups. The distributions and antimicrobial resistance patterns of common pathogens were compared among the groups. The chi-square test was used for statistical analysis.Results:Among the 1 832 children, 1 042 cases had positive urine culture, with the culture positive rate of 56.9%. The top five pathogens detected were Escherichia coli (375 strains, 36.0%), Enterococcus faecium (164 strains, 15.7%), Klebsiella pneumoniae (133 strains, 12.8%), Enterococcus faecalis (95 strains, 9.1%) and Pseudomonas aeruginosa (44 strains, 4.2%). The annual detection rates of gram-negative bacteria (65.3% to 72.9%) were always higher than those of gram-positive bacteria (22.6% to 30.1%). The distributions of pathogens among the years were not significantly different ( χ2 =27.79, P=0.146). In patients with complicated urinary tract infections, the detection rates of Pseudomonas aeruginosa (5.8%(40/688) vs 1.1%(4/354)) and fungi (6.5%(45/688) vs 1.7%(6/354)) were significantly higher than those in patients with simple urinary tract infections ( χ2=12.68 and 11.79, respectively, both P<0.050). Both of Escherichia coli and Klebsiella pneumoniae had the highest resistance rates to ampicillin, which were 87.2%(301/345) and 87.1%(115/132), respectively. The resistance rates of Escherichia coli to amikacin, nitrofurantoin, fosfomycin, cefmetazole, piperacillin/tazobactam, ertapenem, imipenem and meropenem were 1.4%(5/345), 6.1%(21/345), 6.1%(21/345), 8.3%(11/132), 11.6%(40/345), 6.4%(22/345), 4.6%(16/345) and 4.6%(16/345), respectively. The resistance rates of Klebsiella pneumoniae to these drugs were 6.1%(8/132), 37.9%(50/132), 15.2%(20/132), 23.2%(13/56), 26.5%(35/132), 23.5%(31/132), 17.4%(23/132) and 16.7%(22/132), respectively, which were all higher than those of Escherichia coli, and the differences were all statistically significant ( χ2=6.02, 76.17, 9.99, 7.94, 16.04, 28.29, 20.79 and 18.84, respectively, all P<0.050). The resistance rates of Pseudomonas aeruginosa to cefoperazone/sulbactam, piperacillin/tazobactam and ceftazidime were 6.8%(3/44), 4.5%(2/44) and 2.3%(1/44), respectively, while those to carbapenems, amikacin and ciprofloxacin were all 0(0/44). The resistance rate of Enterococcus faecium to ampicillin was 96.8%(153/158), while that of Enterococcus faecalis was 9.1%(8/88). There was no Enterococcus strain resistant to vancomycin, teicoplanin or linezolid. When dynamically comparing the trends of the antimicrobial resistance from 2016 to 2019, the resistance rates of Escherichia coli and Klebsiella pneumoniae to β-lactams (including carbapenems) antimicrobial agents had shown a downward trend. Conclusions:Gram-negative bacteria are still the main pathogens of urinary tract infections in children, with a downward trend of drug resistance rates to β-lactams (including carbapenems) antimicrobial agents.

To determine the physicians′compliance of hour-1 bundle for sepsis. A management system of hour-1 bundle for sepsis was established. The clinical data of 286 sepsis patients were collected, who were classified into 3 months before the bundle (control group), 9 months during process (observation group) and 3 months after bundle (study group). The compliance of hour-1 bundle implementation was compared in three groups. The results showed that with the application and implementation of the management system, the compliance of hour-1 bundle for sepsis in the control group, observation group and study group was 58.3%(28/48), 69.1%(105/152) and 88.4%(76/86) respectively (χ 2=7.053, P=0.029). The 28 day mortality in sepsis patients was 41.7%(20/48), 34.9%(53/152) and 23.3%(20/86) respectively (χ 2=5.576, P=0.062).The management system of hour-1 bundle for sepsis can effectively improve the physicians′ compliance.

Objective:To develop an area under curve (AUC)-based nomogram to predict vancomycin-associated nephrotoxicity in critically ill patients.Methods:This retrospective cohort study included adult patients treated with vancomycin in the intensive care unit at a tertiary teaching hospital from January 2015 to December 2017. Baseline clinical characteristics before vancomycin treatment and pharmacokinetic parameters were collected to establish a prediction model of nephrotoxicity. Univariate analysis was used to screen variables, and multivariate logistic regression analysis was used to establish the prediction model and nomogram.Results:A total of 159 patients met the inclusion criteria, sixty-four were included in the final analysis. Sixteen patients (25%, 16/64) developed vancomycin-associated nephrotoxicity. The following variables were incorporated into the prediction model: vancomycin AUC, estimated glomerular filtration rate (GFR), and combined nephrotoxic drugs. The following equation was established to calculate the probability of nephrotoxicity: logit (P)=-4.83+0.009×AUC-2.87×1 (if GFR>60 ml/min)+2.53×1 (if number of combined nephrotoxic drugs≥2). A nomogram was generated based on the equation. The receiver-operating characteristic curve demonstrated that the AUC of the prediction model was 0.927 (95% CI 0.851-1.000). The cut-off value of the probability of nephrotoxicity was 26.48%. The sensitivity and specificity were 87.5% and 87.5% respectively. Conclusion:The incidence of vancomycin-associated nephrotoxicity is high. The AUC-based nomogram can effectively predict vancomycin-associated nephrotoxicity in critically ill patients.

BACKGROUND: Pulmonary microvascular endothelial cells (PMVECs) were not complex, and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Previous studies have demonstrated that hepatocyte growth factor (HGF), which was secreted by bone marrow mesenchymal stem cells, could decrease endothelial apoptosis. We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide (LPS)-induced endothelial barrier dysfunction and ALI mice. METHODS: In our current study, we introduced LPS-induced PMEVCs with HGF treatment. To investigate the effects of mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in endothelial oxidative stress and mitochondria-dependent apoptosis, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were, respectively, used to inhibit mTOR/STAT3 signaling. Moreover, lentivirus vector-mediated mTORC1 (Raptor) and mTORC2 (Rictor) gene knockdown modifications were introduced to evaluate mTORC1 and mTORC1 pathways. Calcium measurement, reactive oxygen species (ROS) production, mitochondrial membrane potential and protein, cell proliferation, apoptosis, and endothelial junction protein were detected to evaluate HGF effects. Moreover, we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscope in vivo. RESULTS: Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake, which lead to increased mitochondrial membrane potential (JC-1 and mitochondria tracker green detection) and specific proteins (complex I), raised anti-apoptosis Messenger Ribonucleic Acid level (B-cell lymphoma 2 and Bcl-xL), and increased endothelial junction proteins (VE-cadherin and occludin). Reversely, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells. Similarly, mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis. In in vivo experiments of ALI mouse, HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway. CONCLUSION In all, these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level, mitochondria-dependent apoptosis, and endothelial junction protein in ARDS, contributing to the pulmonary endothelial survival and barrier integrity.
Animals ; Apoptosis ; Calcium/metabolism* ; Endothelial Cells/metabolism* ; Endothelium/metabolism* ; Hepatocyte Growth Factor/metabolism* ; Lipopolysaccharides/pharmacology* ; Mammals/metabolism* ; Mechanistic Target of Rapamycin Complex 1/metabolism* ; Mechanistic Target of Rapamycin Complex 2/metabolism* ; Mice ; Mitochondria/metabolism* ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; Respiratory Distress Syndrome ; Sirolimus/pharmacology* ; TOR Serine-Threonine Kinases/metabolism*

Acute respiratory distress syndrome (ARDS) is a common clinical critical condition of the respiratory system, with a high fatality rate and lack of effective drug treatment, hence it is a global medical problem to be solved urgently. Recently, with the in-depth research on extracellular vesicles (EVs) at home and abroad, more and more evidences suggest that EVs play a critical role in the initiation, development and progression of ARDS and have potential clinical application value. The role of different cells derived EVs in ARDS will be reviewed in this paper.

Objective:To analyze the changes in biological characteristics including infectivity, growth and pathogenicity of Chlamydia muridarum ( Cm) after serial passage in vitro in special conditions in order to provide reference for screening attenuated live vaccines and virulence-related genes. Methods:Wild-type Cm strain (G0) was cultured for several passages using conventional cell culture method under alternate unassisted and assisted culture conditions. Then, the 28th generation (G28) of Cm was selected and compared with the parental G0 strain in terms of centrifugation dependence, attaching ability, intracellular growth curve, plaque size and fallopian tube lesions after genital tract infection in a mouse model. Results:Compared with the parental G0 strain, the G28 strain showed significantly decreased dependence on centrifugation during cell infection ( P<0.05) and increased attachment capacity to cells ( P<0.05). No significant differences were observed in the growth curves 32 h after cell infection or in the plaque sizes between the parental G0 and G28 strains. In the in vivo virulence test, fallopian tube lesions were observed in 87.5% of G0-infected mice and 37.5% of G28-infected mice ( P<0.05). Conclusions:Compared with the parental G0 strain, the G28 strain showed significantly enhanced in vitro infection ability, but decreased in vivo pathogenicity, which brought hope for further identification of virulence genes, isolation of attenuated strains with single genotype and development of live attenuated Chlamydia vaccines.