Objective:To investigate the clinical characteristics of omphalocele, and to assess the risk factors associated with adverse outcomes.Methods:A retrospective cohort study was conducted. Clinical data of 224 patients diagnosed with omphalocele, who were hospitalized at Children′s Hospital, Zhejiang University School of Medicine from January 2013 to December 2022, were collected. Based on their discharge outcomes, the patients were classified into 2 groups: favorable outcomes and unfavorable outcomes. Chi-square test or continuity correction χ2 test or Fisher exact probability method, and Mann-Whitney U test were used for intergroup comparisons. Logistic regression analysis was performed to identify risk factors associated with adverse outcomes in omphalocele. Results:Among the 224 patients with omphalocele, 126 were male. A total of 208 patients (92.9%) had favorable outcomes, while 16 patients (7.1%) had unfavorable outcomes. In the unfavorable outcomes group, 14 patients had giant omphaloceles, while 100 patients had giant omphaloceles in the favorable outcomes group. The rates of herniation of more than two intra-abdominal organs in the hernial sac, congenital heart defects, patent ductus arteriosus, pulmonary hypertension, sepsis and infection of the hernial sac, were all higher in the unfavorable outcomes group compared to the favorable outcomes group (all P<0.05). Patients with unfavorable outcomes had longer mechanical ventilation time, duration of oxygen use, duration of parenteral nutrition, hospital stays, and higher rates of parenteral nutrition-associated cholestasis compared to those with favorable outcomes (all P<0.01). Multivariate Logistic regression analysis indicated that pulmonary hypertension ( OR=9.39, 95% CI 1.20-73.32), sepsis ( OR=8.59, 95% CI 1.32-55.86), and congenital heart defects ( OR=6.55, 95% CI 1.11-38.73) were all independent risk factors for adverse outcomes in omphalocele (all P<0.05). Conclusions:Infants with omphalocele are prone to complications such as cardiovascular malformations, infections, and pulmonary hypertension. Adverse outcomes in omphalocele are associated with pulmonary hypertension, sepsis, and congenital heart defects.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

OBJECTIVE: To evaluate the short-term clinical efficacy of external fixation and internal fixation with steel plate in the treatment of unstable distal radius fractures (AO-23C type), based on the principles of Chinese osteosynthesis (CO). METHODS: Forty-eight patients with unstable distal radius fractures between January 2022 and February 2023 were retrospectively analyzed and divided into the CO external fixation group and internal fixation group. CO external fixation group consisted of 25 patients, including 7 males and 18 females, aged from 37 to 56 years old with an average of ( 52.6±11.3) years old. Among them, there were 7 patients of traffic accidents and 18 patients of falls, resulting in a total of 25 patients of closed fractures and no open fractures, the treatment was conducted using closed reduction and CO external fixation. The internal fixation group consisted of 23 patients, comprising 8 males and 15 females, age ranged from 41 to 59 years old, with an average age of(53.3±13.7) years old. Among them, 8 patients resulted from car accidents while the remaining 15 patients were caused by falls. All 23 patients were closed fractures without any open fractures observed. The technique of open reduction and internal fixation with steel plate was employed. The perioperative data, including injury-operation time, operation duration, blood loss, and length of hospital stay, were assessed in both groups. Additionally, the QuickDASH score and visual analogue scale (VAS) were evaluated. Range of motion and grip strength assessment, imaging findings such as palmar inclination angle, ulnar declination angle, radius length, articular surface step, intra-articular space measurements were also examined along with any complications. RESULTS: The follow-up duration ranged from 0 to 24 months, with an average duration of (16.0±3.8) months. The CO external fixation exhibited significantly shorter time from injury to operation (2.4±3.3) d vs (7.4±3.7) d, shorter operation duration (56.27±15.23) min vs (74.10±5.26) min, lower blood loss (14.52±6.54) ml vs (32.32±10.03) ml, and reduced hospitalization days (14.04±3.24 )d vs (16.45±3.05) d compared to the internal fixation group (P<0.05). The QuickDASH score at 12 months post-operation was (8.21±1.64) in the CO external fixation group, while no significant difference was observed in the internal fixation group (7.04±3.64), P>0.05. There were no statistically significant differences in VAS between two groups at 6 weeks, as well as 1 and 3 months post-surgery (P>0.05). Additionally, there were no significant disparities observed in terms of range of motion and grip strength between two groups at the 2-year follow-up after the operation (P>0.05). After 12 months of surgery, the CO external fixation group exhibited a significantly smaller palmar inclination angle (17.90±2.18) ° vs (19.87±3.21) °, reduced articular surface step (0.11±0.03) mm vs (0.17±0.02) mm, and shorter radius length (8.16±1.11) mm compared to the internal fixation group (9.59±1.02) mm, P<0.05. The ulnar deviation angle and intra-articular space did not show any significant difference between two groups (P>0.05). The reduced fell within the allowable range between the CO external fixation group (23 out of 25 cases) and the internal fixation group (21 out of 23 cases) was not statistically significant (P=0.29). There was no significant difference in complications between the two groups(P>0.05). CONCLUSION Both the CO external fixation and open reduction with plate internal fixation demonstrate clinical efficacy in managing unstable distal radius fractures. The CO external fixation offers advantages in shorter injury-to-operation times, reduced intraoperative blood loss, and decreased surgical durations, while radial shortening is more effectively controlled by internal fixation.
Humans ; Male ; Female ; Middle Aged ; Radius Fractures/physiopathology* ; Adult ; Bone Plates ; Fracture Fixation, Internal/methods* ; External Fixators ; Retrospective Studies ; Fracture Fixation/methods* ; Wrist Fractures

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Abstract Alzheimer′s disease(AD) is a common neurodegenerative disease. It has been found that AD is related to various pathogenic factors such as genetics, cardiovascular and cerebrovascular disease, and excessive phosphorylation of tau protein. However, no definitive conclusions on its pathogenesis have been reached. In this paper, the research progress on the pathogenesis of AD inC.elegansmodel and the therapeutic effects of traditional Chinese medicine extracts on AD are reviewed, providing a basis for further research on the alleviating effects of Chinese medicine extracts on AD.

OBJECTIVE To explore the mechanism of Compound lizard powder reducing cisplatin resistance in gastric cancer by regulating glycolytic activity based on phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt） signaling pathway. METHODS Human gastric cancer MKN45 and MKN45/DDP （cisplatin-resistant） cells were cultured in vitro and intervened with different mass concentrations of cisplatin （0.1， 0.2， 0.4， 0.8， 1.6， 3.2 μg/mL） to detect the survival rate， half inhibitory concentration （IC50） and drug resistance index. MKN45/DDP cells were inoculated subcutaneously in the right anterior axilla of nude mice to prepare a transplanted tumor model of gastric cancer. After successful modeling， they were randomly divided into model group， cisplatin group （0.002 g/kg）， Compound lizard powder group （2.8 g/kg） and combination group （the same dose as each single drug group）， with 8 nude mice in each group. Each administration group was given relevant solution， twice a week （cisplatin， i.p.） or twice a day （Compound lizard powder， i. g.）， for 4 consecutive weeks. During the experiment， the body weight of nude mice was monitored， and tumor volume and inhibitory rate of tumor were calculated. The levels of inflammatory factors （tumor necrosis factor- α， interleukin-6） in tumor tissue， the mRNA and protein expressions of multidrug resistance-associated protein 1 （MRP1）， P-glycoprotein （P-gp）， glucose transporter-1 （GLUT1） and lactate dehydrogenase A （LDHA）， as well as the protein expressions of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， hexokinase-2 （HK2） and pyruvate kinase M2 （PKM2） were all detected. RESULTS With the intervention of different concentrations of cisplatin， the survival rate of MKN45/DDP-resistant cells was significantly higher than that of MKN45 parent cells （P＜0.05）. IC50 value of MKN45/DDP and MKN45 cells were（1.052 0±0.221 9） and （0.372 1±0.238 0）μg/mL， and the drug resistant index was 2.827. Compared with the model group， cisplatin group， Compound lizard powder group and combination group all had certain inhibitory effects on the tumor growth in nude mice； the inhibitory rates of tumor increased significantly （P＜0.05）； the levels of inflammatory factors， the mRNA and protein expressions of MRP1， P-gp， GLUT1 and LDHA （except for cisplatin group）， the phosphorylation levels of PI3K and Akt protein （except for cisplatin group） as well as the protein expressions of HK2 and PKM2 were decreased significantly， while the combination group was significantly better than the cisplatin group （P＜0.05）. CONCLUSIONS Compound lizard powder may inhibit tumor growth in transplanted tumor model nude mice with gastric cancer-resistant cells by reducing the secretion of tumor-related inflammatory factors， inhibiting the expression of glycolysis， drug resistance-related proteins and genes， inhibiting the activation of the PI3K/Akt signaling pathway， thus having a certain effect of enhancing cisplatin efficacy and reversing drug resistance.

Background The effects of meteorological factors and air pollutants on ischemic heart disease (IHD) hospitalizations in Urumqi have not been fully understood. Objective To investigate the effects of meteorological conditions (temperature, relative humidity) and common air pollutants [fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), ozone (O₃), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and carbon monoxide (CO)] on the daily hospitalization volume of IHD, and to provide a scientific basis for the development of targeted prevention and management strategies. Methods Basic information of 90622 IHD hospitalized patients in Urumqi City was collected from January 1, 2014 to December 31, 2022, and daily air pollutant concentration data and meteorological data were collected during the same period. The meteorological data included daily mean temperature, daily maximum temperature, daily minimum temperature, and daily mean relative humidity, and the common air pollutants included PM_2.5, PM₁₀, daily maximum 8-h average concentration of O₃ (O₃_8 h), SO₂, NO₂, and CO. Descriptive statistical analyses (mean, standard deviation, and quartiles) were performed on the collected data. A distribution lag nonlinear model (DLNM) based on time-stratified case-crossover design was established to estimate the lagged effects (RR) as well as the cumulative lagged effects (RR_cum) of daily mean temperature, relative humidity, and different air pollutants on the number of IHD admissions, stratified by gender and age (<60 and ≥60 years). Subsequently, a generalized additive model (GAM) was used to explore the effects of cold waves (≤ P₅ of the daily minimum temperature and lasting ≥3 d) versus heat waves (≥ P₉₅ of the daily maximum temperature and lasting ≥3 d) on IHD hospitalizations and the potential interactions between temperature and the more influential air pollutants [particulate matter (PM) and O₃_8 h] on IHD hospitalizations. Results The maximum number of IHD hospitalizations in a single day in Urumqi from January 1, 2014 to December 31, 2022 was 100, and the average daily number of hospitalized IHD patients was 27. Daily mean temperature, relative humidity, and air pollutants had different nonlinear relationships and hysteresis with IHD hospitalizations. Extremely low temperatures (<P₁: −18 °C) showed the greatest risk to admission for the total IHD population at a cumulative lag of 31 d (lag0-31) (RR_cum=2.092, 95%CI: 1.261,3.471). Female [lag0-31, RR_cum and 95%CI: 3.416 (2.296,5.082)] and people ≥60 years old [lag0-31, RR_cum and 95%CI: 2.356 (1.681,3.303)] were more sensitive to extremely low temperatures. The risk of IHD hospitalization was greatest on lag20 for cold waves (RR=1.242, 95%CI: 1.053, 1.465), and no lagged effect of heat waves on the number of IHD hospitalizations was found. There was a positive interaction (SI >1, P<0.001) between temperature, PM, and O₃_8 h on the risk of IHD hospitalization, especially for low temperature-high PM and O₃_8 h. Conclusion Both low temperature and high pollutant concentrations associate with an increase in IHD hospitalizations with lagged effects in Urumqi from 2014 to 2022, while cold waves associate with a higher risk of IHD admissions. Females and people aged 60 years and older are at high risk.

Tight-junction (TJ) is a complex supramolecular entity composed of complete membrane proteins, membranes and soluble cytoplasmic proteins, which is distributed in almost all barrier structures in the body. It can maintain the polarity of epithelial cells, close the intercellular space and prevent the overflow of materials in the epithelial space, and is a highly dynamic signaling entity. Occludin is one of the most representative members of TJ proteins, mainly responsible for sealing intercellular connections, maintaining intercellular permeability, and participating in maintaining the integrity of vascular endothelium. The integrity of occludin is related to the integrity of TJ, and the function of occludin is often associated with the barrier properties of various tissues, and the abnormal expression of occludin is related to the occurrence and development of various diseases. Occludin contains abundant Ser and Thr residues and has multiple phosphorylation sites. Phosphorylation is necessary for the combination of occludin and TJ, which can regulate the location of occludin, regulate the expression of occludin, and enhance the permeability and barrier function of TJ. Therefore, phosphorylation regulation is a mechanism that cannot be ignored in the regulation of occludin function. Occludin also interacts with many other proteins, such as co-forming the cytoskeleton with ZO-1, and is regulated by a variety of transcription factors. Studies have confirmed that in pathological conditions, a variety of signaling pathways can disrupt the integrity of cell barrier by regulating the expression and distribution of occludin. Myosin light chain kinase (MLCK) signal transduction pathway is one of the important ways to regulate the structure and function of TJ. It influences the expression of occludin by altering the cytoskeleton. MLCK mainly uses the phosphorylation of myosin light chain (MLC) as a medium to promote actin contraction, secondary decomposition of tightly binding proteins, resulting in increased or changed cellular barrier permeability, and increased MLC phosphorylation is also a biochemical marker of actomyosin contraction. Activation of MLCK causes Thr18 and Ser19 phosphorylation of MLC, which promotes the assembly of myosin II into myosin fibers and activates the hydrolysis of ATP, which relaxes the intercellular connections and reduces the ability of upper cortex to resist external invaders. Protein kinase C (PKC) plays an important role in the regulation of tightly connected signaling molecules, affecting the dynamic changes of paracellular permeability. PKC pathway is a key link in many cell signal transduction pathways, which influences all aspects of cell activities by catalyzing Ser/Thr residues phosphorylation of membrane proteins and many enzyme proteins. After PKC activation, it can regulate cellular barrier function by phosphorylating occludin and inducing its redistribution, and directly affect TJ action. Specific PKC subunits such as PKCα, PKCδ and PKCγ are activated and act on occludin molecules to promote their phosphorylation and cause the increase of TEER. The increase of TEER helps to regulate intercellular TJ and enhance the tightness of intercellular connections. Mitogen-activated protein kinases (MAPK) are usually activated by inflammatory factors, during which different signal transduction pathway subfamilies are formed to regulate occludin expression and affect tight junction and mucosal barrier functional integrity. Meanwhile, occludin is easily affected by various factors (such as cytokines and flora toxins), and abnormal expression of occludin will lead to structural damage of TJ and further damage of the intercellular barrier. Therefore, this paper summarizes the molecular structure and physiological function of occludin, and further summarizes its related signal regulation pathways and influencing factors, in order to provide theoretical support for maintaining the integrity of barrier function of occludin.

OBJECTIVE To establish the HPLC fingerprint and content determination of five components in Ranunculus sceleratus L.. METHODS The separation was developed on an Agilent ZORBAX SB C18 chromatographic (4.6 mm×250 mm, 5 μm)column by gradient elution with methanol(A)-0.1 % phosphoric acid aqueous solution(B) as mobile phase to establish HPLC fingerprint of Ranunculus sceleratus L.. Combined with similarity evaluation, cluster analysis, principal component analysis, and orthogonal partial least squares-discriminant analysis, the quality of 13 batches of Ranunculus sceleratus L. was evaluated. RESULTS Thirteen batches of Ranunculus sceleratus L. samples were calibrated with 20 common peaks, of which 5 common peaks were identified, and the similarity ranged from 0.874 to 0.984. The results of cluster analysis and principal component analysis were basically the same, indicating that there might be differences in the content of chemical components of Ranunculus sceleratus L. in different regions. Protocatechuic aldehyde, caffeic acid, ferulic acid, hyperoside and isoquercitrin were determined in thirteen batches of Ranunculus sceleratus L., and their contents were 0.016−0.035, 0.010−0.070, 0.010−0.029, 0.016−0.051, 0.028−0.086 mg·g–1, respectively. CONCLUSION The established HPLC fingerprint and content determination method is simple, stable, and reliable, which can be used for qualitative analysis and provide reference to quality evaluation and resource utilization of Ranunculus sceleratus L..