ObjectiveTo explore the clinical characteristics and risk factors for 30-day mortality in hospitalized patients with bloodstream infections (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). MethodsData were obtained retrospectively from the electronic medical records of inpatients at a tertiary A-grade hospital in Shanghai from January 2016 to December 2023. The collected variables included age, gender, department, surgical treatment, empirical antibiotic therapy, Pitt Bacteremia score (PBS), Charlson comorbidity index (CCI), INCREMENT-CPE score (ICS), length of hospital stay, the time from CRKP-BSI to discharge and, etc. The follow-up period ended upon discharge, with the follow-up outcomes defined as in-hospital mortality or discharge. The endpoint was defined as death within 30 days (including day 30) caused by CRKP-BSI or infection-related complications. Patients who survived within 30 days after CRKP-BSI were classified into the survival group, while those who died within 30 days were classified into the death group. Independent risk factors for 30-day mortality in patients with CRKP-BSI were analyzed using univariate and multivariate Cox regression analysis. ResultsA total of 71 hospitalized patients with CRKP-BSI, comprising 51 males and 20 females, with an average age of (65.12±18.25) years, were included during the study period. The M (P₂₅, P₇₅) of hospital stay were 37.00 (24.00, 56.00) days, and M (P₂₅, P₇₅) of the duration from CRKP-BSI to discharge or death were 18.00 (7.00, 35.00) days. There were 20 deaths (28.17%) in the death group and 51 survivors (71.83%) in the survival group. The results of multivariate Cox regression analysis showed that the ICS as an independent risk factor for 30-day mortality in CRKP-BSI patients (HR=1.379, 95%CI: 1.137‒1.671, P=0.001). Each 1-point increase in the ICS was associated with a 37.9% increase in the risk of mortality. ConclusionThe ICS is found to be a risk factor for 30-day mortality in patients with CRKP-BSI, which may facilitate the prediction for the risk of 30-day mortality and thereby support clinical decision-making for patients with CRKP-BSI.

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Human epidermal growth factor receptor 2 (HER2) is a key therapeutic target for breast cancer. With the wide application of anti-HER2 and HER2 antibody-drug conjugates such as trastuzumab, pertuzumab, trastuzumab emtansine, and trastuzumab deruxtecan, the survival of patients with advanced HER2-positive breast cancers have been significantly improved. However, the subsequent drug-induced interstitial lung disease (DILD) has gradually become an important complication affecting the therapeutic effect and safety. However, the clinical understanding of interstitial lung disease (ILD) caused by this type of drugs is still insufficient, the management lacks unified standards, and the molecular mechanism has not been fully clarified. This study, through two clinical cases of severe DILD, explores the pathogenesis, treatment strategies, risk factors and follow-up monitoring requirements of ILD caused by HER2-targeted drugs, providing a scientific basis for optimizing the clinical diagnosis and treatment plan.

BackgroundPatients demonstrating depressive disorder with psychotic symptoms often have increased risk of death and poor prognosis. A large amount of research has explored the factors influencing psychotic symptoms in adult patients with depressive disorder， but few has focused on adolescent patients. ObjectiveTo explore the influencing factors of psychotic symptoms in adolescent patients with depressive disorder， so as to provide references for early screening and intervention in clinic. MethodsA total of 96 adolescent patients who met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） for depressive disorder and were seen in the psychiatry departments of Chaohu Hospital of Anhui Medical University and The Fourth People's Hospital of Hefei from September 2022 to January 2023 were included. Another 56 healthy individuals from the health examination center of Chaohu Hospital of Anhui Medical University were concurrently recruited as control group. Patients were assigned into psychotic group （n=32） and non-psychotic group （n=64） according to the presence or absence of psychotic symptoms. Hamilton Depression Scale-24 item （HAMD-24）， Positive and Negative Syndrome Scale （PANSS）， Positive and Negative Suicide Ideation （PANSI） and Childhood Trauma Questionnaire-Short Form （CTQ-SF） were used for evaluation. Plasma brain-derived neurotrophic factor （BDNF） concentration was obtained using Meso Scale Discovery electrochemiluminescence assay. Pearson and Spearman correlation analysis were adopted to determine the correlation of PANSS positive symptom subscale score with plasma BDNF concentration and clinical characteristics of adolescent depression patients with psychotic symptoms. Binary Logistic regression analysis was used to identify the factors influencing the presence of psychotic symptoms in adolescent patients with depressive disorder， and multiple linear regression analysis was utilized to screen the factors affecting the severity of psychotic symptoms. ResultsThe plasma BDNF concentration of adolescent patients with depressive disorder was lower than that of control group （t=-3.080， P<0.01）.The plasma BDNF concentration of psychotic group was lower than that of non-psychotic group （t=2.418， P<0.05）， while the body mass index （BMI） PANSI scores， CTQ-SF scores and HAMD-24 total scores were all higher than those of non-psychotic group （t=-2.024， -2.530， -2.187， -4.977， P<0.05 or 0.01）. Correlation analysis showed that PANSS positive symptom subscale scores were negatively correlated with anxiety/somatization factor score and weight factor score in HAMD-24 of psychotic group （r=-0.438， -0.498， P<0.05 or 0.01）. Binary Logistic regression showed that BMI， plasma BDNF concentration， HAMD-24 total scores and cognitive dysfunction factor score were the influencing factors of psychotic symptoms in adolescent patients with depressive disorder. Multiple linear regression analysis demonstrated that weight factor scores （β=-0.349， P<0.05） and anxiety/somatization factor score （β=-0.433， P<0.05） in HAMD-24 were the factors influencing the severity of psychotic symptoms. ConclusionHigh BMI， low plasma BDNF concentration， severe depressive symptoms and cognitive dysfunction may be the risk factors of psychotic symptoms in adolescent patients with depressive disorder， furthermore， BMI and anxiety symptoms are found to be associated with the severity of psychotic symptoms. ［Funded by Scientific Research Fund Project of Anhui Institute of Translational Medicine （number， 2022zhyx-B01）； Central Finance Supported Provincial Key Clinical Specialty Construction Project of Anhui Province in 2019］

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Objective:To investigate the value of multi-parametric analysis based on dual-layer detector spectral CT (DLCT) in predicting the initial recurrence risk for papillary thyroid carcinoma (PTC).Methods:From November 2021 to October 2022, 102 PTC patients confirmed by pathology were retrospectively collected at the First Affiliated Hospital of Nanjing Medical University in this cross-sectional study. There were 25 males and 77 females, with an age of (42±13) years old. The initial recurrence risk assessment for PTC patients was categorized into a low-risk group (75 cases) and an intermediate-high-risk group (27 cases). Clinical data, including age, gender, body mass index, history of nodular goiter, history of Hashimoto thyroiditis, and preoperative thyroid function, were collected. Tumor morphological features, including size, location, shape, aspect ratio, the degree of thyroid capsule contact, calcification, and cystic change, were evaluated. Quantitative DLCT parameters, including iodine concentration (IC), standardized iodine concentration (NIC), effective atomic number (Z eff), standardized effective atomic number (NZ eff), electronic density (ED), CT values under different energy levels (40-200 keV, 30 keV intervals) and slope of energy spectrum curve (λ HU) both in the arterial and venous phase were measured. The differences in clinical, morphological features, and spectral CT quantitative parameters between the two groups were compared using independent sample ttest, Mann-Whitney U test, or χ2 test. Multivariate logistic regression analyses were used to construct three models based on clinical and morphological features, quantitative DLCT parameters and their combination, respectively. The receiver operating characteristic curve was used to evaluate the predictive performance of these models for the initial recurrence risk of PTC patients, and the area under the curve (AUC) was compared using the DeLong test. Results:Significant differences were found in gender, lesion long diameter, lesion short diameter and calcification between the low-risk group and intermediate-high-risk groups ( P<0.05). The arterial phase IC, arterial phase Z eff, arterial phase λ HU, arterial phase CT 40 keV, venous phase NIC and venous phase NZ eff in intermediate-high-risk group were significantly lower than those in the low-risk group ( P<0.05). The logistic regression analysis revealed that the clinical model included gender ( OR=2.895, 95% CI 1.047-8.002, P=0.040) and lesion long diameter ( OR=1.142, 95% CI 1.042-1.251, P=0.004), with an AUC of 0.720, sensitivity of 63.0%, and specificity of 78.7% in predicting the initial recurrence risk of PTC patients. The DLCT quantitative parameter model included arterial phase IC ( OR=0.580, 95% CI 0.370-0.908, P=0.017), venous phase NIC ( OR=0.077, 95% CI 0.011-0.536, P=0.010), and venous phase NZ eff ( OR=0.002, 95% CI 0.001-0.103, P=0.009), with an AUC of 0.774, sensitivity of 71.9%, and specificity of 70.0%. The AUC of the combined model was 0.857, with a sensitivity of 74.1%, and specificity of 88.0%, outperforming the clinical model ( Z=2.92, P=0.004) and the DLCT quantitative parameter model ( Z=2.07, P=0.046). Conclusion:Multi-parametric analysis based on DLCT can help predict the initial recurrence risk for PTC, and combining it with clinical and morphological features, the predictive accuracy can be improved.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Female ; Humans ; Adenocarcinoma in Situ ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections ; Cervix Uteri/pathology* ; Adenocarcinoma/pathology* ; Papillomaviridae ; DNA, Viral

Objective:To evaluate the role of volume management guided by extravascular lung water index(EVLWI) in improving the clinical outcomes and cardiac function for patients with cardiogenic shock.Methods:This study was a single-center, prospective cohort study. Patients with cardiogenic shock admitted to the Department of Cardiovascular Medicine, Shanghai East Hospital from July 2022 to December 2023 were enrolled. Patients were matched 1∶1 by propensity score and divided into EVLWI group and control group. In the control group, the volume management strategy was determined by the attending physician based mainly on conventional factors, including clinical features, biochemical assessments, and certain blood pressure measurements. In EVLWI group, the volume management plan was formulated by integrating conventional factors with EVLWI derived from pulse index continuous cardiac output (PiCCO) monitoring. Baseline clinical data, in-hospital treatment, and hemodynamic data were collected. Major adverse cardiovascular events and cardiac function related parameters were compared at 30 d after treatment between the two groups. Baseline EVLWI levels were compared between the non-survivors and the survivors in the EVLWI group. The receiver operating characteristic curve was plotted to assess the accuracy of baseline EVLWI and central venous pressure in predicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock, and subgroup analysis was performed according to ischemic/non-ischemic etiology and with/without use of inotropic drugs. Kaplan-Meier curve was used for survival analysis, with log-rank tests comparing all-cause mortality, cardiac death, and readmission rate for heart failure at 30 d after treatment.Results:A total of 200 patients with cardiogenic shock were enrolled, aged (71.35±12.82) years, 144(72%) males, EVLWI group and control group 100 patients each. Compared with the control group, EVLWI group had lower all-cause mortality (16%(16/100) vs. 42%(42/100), log-rank P<0.01), cardiac death (14%(14/100) vs. 34%(34/100), log-rank P<0.01), and readmission rate for heart failure (4%(4/100) vs. 12%(12/100), log-rank P=0.03) at 30 d after treatment. Subgroup analysis showed that EVLWI-guided volume management was associated with lower all-cause mortality at 30 d after treatment in patients with cardiogenic shock of ischemic or non-ischemic etiology and with or without inotropic drugs (all P<0.05). In EVLWI group, baseline EVLWI levels were higher in non-survivors than those in survivors [(15.99±6.47) ml/kg vs.(9.75±2.55) ml/kg, P<0.01]. The baseline EVLWI could predicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock, with an area under the receiver operating characteristic curve of 0.84 (95% CI: 0.75-0.94, P<0.01), while the baseline central venous pressure had no predicting value ( AUC=0.54, 95% CI: 0.40-0.69, P=0.60). The optimal cutoff value of EVLWI in pridicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock was >10.3 ml/kg. With the optimization of hemodynamic parameters, left ventricular ejection fraction was improved in EVLWI group, and serum levels of N-terminal pro-brain natriuretic peptide, creatinine, alanine aminotransferase and lactic acid were decreased (all P<0.05). Conclusion:EVLWI-guided volume management exerts a beneficial effect on therapeutic decision-making and improves clinical outcomes and cardiac function in patients with cardiogenic shock.

Objective To explore the potential categories of self-efficacy in patients with rheumatoid arthritis(RA),analyze their influencing factors,and provide references for the development of personalized care measures.Methods Patients with RA who visited the rheumatology and immunology outpatient department of a tertiary hospital in Changzhou from March 2022 to March 2023 were selected.A general information questionnaire,the Chinese version of the Rheumatoid Arthritis Self-Efficacy Scale(C-RASE),and Compliance Questionnaire Rheumatology(CQR)were used to investigate RA patients.Latent class analysis was used to classify self-efficacy,and logistic regression analysis was conducted to explore the influencing factors of self-efficacy.Results A total of 219 subjects were included in the survey.The score of C-RASE was(100.68±12.64).The self-efficacy of RA patients was divided into a high efficacy-low support group(105.18±10.18),a moderate efficacy-diverse needs group(93.21±4.16),and a low efficacy-high fatigue group(84.07±13.96).Logistic regression analysis showed that disease duration(OR=1.062,P=0.024),education(OR=5.405,P=0.036;OR=12.347,P=0.021),and erythrocyte sedimentation rate(OR=1.019,P=0.020;OR=1.019,P=0.027)were factors affecting patients'self-efficacy.The treatment compliance scores of the 3 latent class categories(F=10.902,P＜0.001)and the rate of good treatment compliance(x2=16.053,P＜0.001)were statistically significant.Conclusion RA patients exhibit significant heterogeneity in their self-efficacy levels,and there are variations in treatment adherence among patients in different self-efficacy categories.Nurses should prioritize the attention towards the population groups with moderate efficacy-diverse needs,as well as the groups with low efficacy-high fatigue,implementing cognitive behavioral interventions to assist them in setting clear goals and providing specific plans and guidance to improve their health outcomes.