ObjectiveTo understand the infection characteristics and drug resistance of carbapenem-resistant Serratia marcescens (CRSM) in a general hospital in Shanghai, and to provide a theoretical basis for clinical anti-infective treatment and prevention of drug-resistant bacteria. MethodsClinical data on cases with CRSM infections detected in clinical specimens at a gradeⅢ level A general hospital in Shanghai from June 2022 to June 2024 were retrospectively collected, and their clinical distributions, factors of hospital-acquired infections, prognosis, and drug-resistant situation were analyzed simultaneously. ResultsA total of 38 cases with CRSM were detected from June 2022 to June 2024, and the number of CRSM strains accounted for 25.00% (38/152) of the number of SM strains. The 38 CRSM infection samples were all derived from sputum. CRSM were distributed in 9 clinical departments, and the top 3 departments having the highest percentages of CRSM among SM strains, were intensive care unit (ICU) (78.79%, 26/33), gastrointestinal surgery department (57.14%, 4/7), and thyroid hernia surgery department (50.00%, 1/2). Among the 38 patients with CRSM infections, 8 cases were identified as hospital-acquired infection, resulting in a hospital-acquired infection rate of 21.05. The mortality rate of the 38 cases of CRSM infected patients within 30 days after detection of CRSM was 23.68% (9/38). The results of multivariate logistic regression analysis showed that sequential organ failure assessment (SOFA) score ≥6.5 points (OR=15.33, P<0.001), septic shock (OR=4.85, P=0.032), and suffering from neoplastic diseases (OR=0.12, P=0.018) were the related factors for death within 30 days after the detection of CRSM in patients with CRSM infection. The results of drug sensitivity test showed that the 38 cases of CRSM exhibited 100.00% (38/38) sensitivity to trimethoprim/sulfamethoxazole, tigecycline, or ceftazidime/avibactam; demonstrated high resistance toβ-lactams except for ceftazidime (18.42%, 7/38), the latter of which was one of the third-generation of cephalosporins; showed elevated resistance to fluoroquinolones [levofloxacin (89.47%, 35/38), ciprofloxacin (94.74%, 36/38)]; maintained good tetracycline sensitivity [doxycycline (97.37%, 37/38), minocycline (76.32%, 29/38)]; and displayed high susceptibility to the aminoglycoside gentamicin (94.74%, 36/38) and elevated resistance to tobramycin (86.84%, 34/38). The detection rate of serine carbapenemase in the 38 strains of CRSM was 100.00%, while all strains tested negative for metallo-β-lactamases. ConclusionFrom June 2022 to June 2024, the detection rate of CRSM in a gradeⅢ level A general hospital in Shanghai was relatively high, especially in the ICU. CRSM has a high resistance rate to commonly used antibacterial drugs such as the first and second-generation cephalosporins, quinolones, and polypeptide antibacterial drugs. Therefore the dynamics of drug-resistant bacteria should be tracked in a timely manner to guide the rational clinical application of antibacterial drugs.

OBJECTIVE: To determine risk factors for cutout failure in geriatric intertrochanteric fracture patients after cephalomedullary nail fixation. METHODS: A retrospective review of 518 elderly patients who underwent cephalomedullary nail fixation for intertrochanteric fractures between January 2008 and August 2018 was conducted, including 167 males and 351 females, age from 65 to 97 years old. All patients were followed up for at least one year after surgery and divided into a healed group and a cutout group based on whether the hip screw cutout occurred. Among all patients, 10 cases experienced hip screw cutout. The general information, surgical data, and radiological data of the two groups were compared, and risk factors influencing hip screw cutout were analyzed. Propensity score matching was then performed on the cutout group based on gender, age, body mass index(BMI), and American Society of Anesthesiologists(ASA), and 40 patients from the healed group were matched at a ratio of 1∶4. Key risk factors affecting hip screw cutout were further analyzed. Multivariable logistic regression analysis was conducted to evaluate associations between variables and cutout failure. RESULTS: There were no statistically significant differences between the healed group and the cutout group in terms of age, gender, BMI, ASA, and AO classification. However, statistically significant differences were observed between the two groups in terms of reduction quality(P=0.003) and tip-apex distance(TAD), P<0.001. Multivariate analysis identified poor reduction quality OR=23.138, 95%CI(2.163, 247.551), P=0.009 and TAD≥25 mm OR=30.538, 95%CI(2.935, 317.770), P=0.004 as independent risk factors for cutout failure. CONCLUSION The present study identified poor reduction quality and TAD≥25 mm as factors for cutout failure in geriatric intertrochanteric fractures treated with cephalomedullary nails. Further studies are needed to calculate the optimal TAD for cephalomedullary nails.
Humans ; Male ; Female ; Hip Fractures/surgery* ; Aged, 80 and over ; Aged ; Risk Factors ; Retrospective Studies ; Fracture Fixation, Intramedullary/adverse effects* ; Bone Nails ; Bone Screws

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the aggregation of α-synuclein (α-syn) and dysregulated synaptic vesicle (SV) recycling. Emerging evidence suggests that ferroptosis is the target of PD therapy. However, the identification of effective anti-ferroptosis treatments remains elusive. This study explores the therapeutic potential of low-intensity ultrasound (US) in modulating SV recycling and anti-ferroptosis in cellular and animal models of PD. We demonstrate that optimized US stimulation (610 kHz, 0.2 W/cm²) activates Piezo1 channel-mediated fast endophilin-mediated endocytosis, which promotes SV recycling and synaptic function, presenting with increased frequency and amplitude of both spontaneous excitatory synaptic currents and miniature excitatory postsynaptic currents. Repaired SV recycling in turn reduces the accumulation of α-syn expression and ferroptotic cell death. These findings support the potential of noninvasive ultrasonic neuromodulation as a therapeutic strategy for PD and lead to meaningful health outcomes for the aging population.
Animals ; Ferroptosis/physiology* ; Synaptic Vesicles/metabolism* ; Dopaminergic Neurons/metabolism* ; Ion Channels/metabolism* ; Mice ; Ultrasonic Waves ; Humans ; Male ; Mice, Inbred C57BL ; Endocytosis/physiology* ; alpha-Synuclein/metabolism*

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Aim To predict and validate the mechanism of wenshen xuanbi tang(WSXBT) in treatment of osteoporosis (OP) based on network pharmacology, molecular docking techniques and in vivo experimental techniques. Methods Network pharmacology was used to screen the key ingredients and core targets of WSXBT for the treatment of osteoporosis. Metascape database was used for gene ontology (GO) biological process enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis of core targets. AutoDockTools 1. 5. 7 software was applied in molecular docking to simulate the binding activity of key active ingredients to core targets. To study the efficacy of WSXBT on rats with osteoporosis and to verify the related targets and pathways, rat models of osteoporosis were established by excising the bilateral ovaries of rats. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum OPG, PINP and RANKL content. Biomechanical tester was applied to test the biomechanics of rat femurs. Micro-CT was applied to detect the femoral bone density. Then, Western blot was employed to measure the protein expression levels of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt). Results A total of 156 active ingredients of WSXBT were screened, involving 229 potential targets, 23 core targets and 145 signaling pathways. The molecular docking results showed that five key ingredients, including quercetin, kaempferol, naringenin, isobavachin and licochalcone a, possessed good binding ability to the core targets of PIK3R1 and AKT1. The results of in vivo experiments showed that WSXBT could significantly increase bone density, improve bone tissue microstructure, enhance femur biomechanics and increase PINP expression and OPG/RANKL ratio in rats with osteoporosis. Results of WB showed that WSXBT significantly increased p-PI3K/PI3K and p-Akt/Akt ratios. Conclusions WSXBT could improve bone mineral density in postmenopausal osteoporotic rats through PI3K/ Akt signaling pathway and increasing OPG/RANKL ratio.

Fluorescence microscopy is a vital tool in life science research, but the diffraction nature of light limits further observation of cells. Super-resolution imaging techniques provide deeper insights into cellular structures, including stimulated emission depletion microscopy (STED), structured illumination microscopy (SIM), and single-molecule localization microscopy (SMLM). Each of these methods offers unique advantages and principles that push the boundaries of spatial resolution beyond conventional diffraction limits. Among these techniques, SMLM stands out for its exceptional resolution, offering nanometer resolution and becoming a powerful tool for obtaining high-resolution images. SMLM is particularly valuable for studying the spatial distribution and interactions of organelles and macromolecular complexes. Following the award of the Nobel Prize in Chemistry in 2014, super-duper resolution imaging techniques were listed as one of Nature’s seven technologies to watch in 2024. The development of these techniques remains an important area of research. We introduce the development of multi-color SMLM, three-dimensional (3D) SMLM, and nanoscale resolution microscopes. We describe several methods to achieve multi-color SMLM. Sequential imaging and Exchange-PAINT require image targets in sequence, excitation or emission spectral demixing can obtain multi-color images simultaneously based on spectral difference between fluorescent dyes, dual-channel spectroscopic SMLM to achieve simultaneous imaging and spectral analysis of each molecule, and techniques based on binding kinetics of PAINT achieve multi-color by designing the blinking behavior of targets with engineered binding frequency and duration in DNA-PAINT. We then discuss various approaches for 3D imaging. Point spread function (PSF) engineering techniques manipulate the shape and properties of the PSF to improve 3D localization accuracy. Multi-plane imaging methods capture images from different focal planes and reconstruct them to obtain 3D information. Interferometry methods use single molecule interference to achieve high precision in axial localization, providing another way for high resolution 3D nanoscopy. Finally, we highlight advances in new nanoscale resolution microscopes based on modulated illumination patterns, including minimal photon fluxes (MINFLUX), repetitive optical selective exposure (ROSE), ROSE-Z, SIMFLUX, SIMPLE, and ModLoc. MINFLUX is known for its ability to achieve ultra-high resolution by detecting minimal photon fluxes from single molecules using a doughnut-shaped excitation spot to spatially modulate excitation intensities. Typically, we focus on ROSE and ROSE-Z, which outperform other techniques, using a resonant mirror to eliminate localization errors caused by fluorescence blinking. Recently, resolution enhancement by sequential imaging (RESI) and one nanometre expansion (ONE) was introduced to achieve resolution down to the Ångström scale. Nanoscopy serves as a new role between super resolution microscopy and structural biology and will lead to more discoveries in complex biological systems. Overall, this article provides a comprehensive overview of current advances in super-resolution imaging techniques, highlighting their contributions to overcoming the diffraction limit and enabling detailed observation of nanoscale biological structures, and provides an outlook on promising new techniques and applications. Through detailed descriptions of the principles, benefits, and applications of multi-color and 3D techniques, the article highlights new nanoscale imaging techniques that are expanding our ability to visualize and understand the intricate details of molecular and cellular processes. We hope that this article can be a primer resource for both newcomers and seasoned practitioners of SMLM.

Objective:To analyze the difference and reliability of blood 17-hydroxyprogesterone (17-OHP), an indirect screening index for congenital adrenal hyperplasia (CAH), between preterm and full-term infants.Methods:In this retrospective cross-sectional study, a total of 210 285 newborns who underwent CAH screening at the Neonatal Screening Center of Shanghai Children′s Hospital from January 2019 to December 2022 were collected, including 14 312 premature infants and 195 973 full-term infants.The concentration of 17-OHP in dried blood spots on filter paper was determined by an automatic fluorescence analyzer.The distribution of 17-OHP levels in preterm and full-term infants and its statistical index were analyzed.The Kolmogorov-Smirnov test was used for normal distribution.The skewed distribution data was converted into approximately normal distribution using Box-Cox.Outliers were eliminated by the interquartile range method.The cumulative frequency distribution map was drawn by R language programming.The 99.5 th percentile value was used as the screening threshold and compared with the reference value given by the manufacturer or laboratory and with the reference change value (RCV). Results:According to the threshold provided by the laboratory, 26.76‰ of premature infants were tested positive in preliminary screening, and 4 were confirmed with an incidence of 1∶3 578, while 0.79‰ of full-term infants were tested positive in preliminary screening, and 11 were confirmed with an incidence of 1∶17 816.The thresholds for CAH screening established indirectly were 20.35 nmol/L in preterm infants and 10.78 nmol/L in full-term infants.The relative deviations between the indirect CAH screening thresholds and the manufacturer′s or laboratory′s CAH screening thresholds were higher than the RCV, respectively.According to the indirect CAH screening thresholds, the negative and positive coincidence rates of 65 samples in 13 batches from the Centers for Disease Control and Prevention interlaboratory quality assessment program in the United States reached 100%.A retrospective analysis of 210 285 neonates showed that 17-OHP concentration was higher than the screening threshold in all CAH-positive neonates.The application of this screening threshold reduced the false positive rate of preterm infants by 59.79%.Conclusions:It is feasible to establish the CAH screening thresholds for premature and full-term infants by an indirect method, which can improve the efficiency of screening and provide better diagnostic basis for clinical practice.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To investigate the prevalence of cataracts, the surgical coverage, and postoperative visual acuity of adults in Ningxia.Methods:A cross-sectional study using multistage cluster random sampling was conducted.Ten survey sites in Ningxia were selected and the population aged 18 years and over was surveyed with questionnaire, height and weight measurements, visual acuity, intraocular pressure, fundus photography and slit-lamp examinations.Cataract prevalence and its influencing factors were analyzed.Cataract prevalence, surgical coverage and presenting visual acuity (PVA) and best corrected visual acuity (BCVA) after surgery were investigated in different age groups of the examined population.The study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the People's Hospital of Ningxia Hui Autonomous Region (No.[2023]-LL-010).Participants signed informed consent prior to the examination.Results:A total of 6 145 people should be examined, and 5 721 people were actually examined, with an examination rate of 93.10%.The study population consisted of 2 558 males, accounting for 44.71%, and 3 163 females, accounting for 55.28%, with ages ranging from 18 to 93 years old and an average age of (64.27±13.48) years.Among them, 1 180 patients diagnosed with cataract, with a cataract prevalence of 20.62%.The prevalence of cataract increased with age and decreased with education level, showing statistically significant differences ( χ2=1 091.32, 581.92; both at P<0.01).The prevalence of cataract was significantly higher among people with hypertension, diabetes mellitus, hyperlipidemia, and coronary heart disease than those without these diseases ( χ2=274.65, 118.15, 78.05, 182.71; all at P<0.01).Cataract surgery was performed in 245 cases in the cataract patient population, with a surgical coverage rate of 20.76%.Of the 245 cases, 229 cases were implanted with IOLs, with an implantation rate of 93.40%.The social burden rate of cataract blindness was 2.29%, and increased with age.Of the 339 eyes that underwent cataract surgery, 241 had a PVA≥0.3, accounting for 71.09%, and 272 had a BCVA≥0.3, accounting for 80.24%. Conclusions:In Ningxia, cataracts are still the main cause of vision impairment and blindness in the elderly, and the social burden rate of cataract blindness is high.Moreover, the coverage rate of cataract surgery is low, so both the coverage and quality of surgery need improvement.