ObjectiveTo investigate the value of Fried Frailty Phenotype （FFP）， liver frailty index （LFI）， and Short Physical Performance Battery （SPPB） in predicting 2-year all-cause mortality and decompensation events in patients with liver cirrhosis. MethodsA total of 277 patients with liver cirrhosis who were hospitalized in Beijing Friendship Hospital， Capital Medical University， from December 2020 to December 2021 were enrolled， and FFP， LFI， and SPPB were used to assess the state of frailty. Based on the scores of each tool， these patients were divided into frail and non-frail groups. These three tools were compared in terms of consistency and independent predictive performance. The primary endpoints were 2-year all-cause mortality rate and composite endpoints （death+decompensation events）， and the Cox regression analysis， the receiver operating characteristic （ROC） curve， net reclassification index （NRI）， and integrated discrimination improvement （IDI） index were used to analyze the predictive value of the three tools. Normally distributed continuous data were compared between two groups using the independent samples t-test， while non-normally distributed continuous data were compared using the Mann-Whitney U test. Categorical data were compared between groups using the chi-square test or Fisher’s exact test. The agreement among different frailty tools was evaluated using Cohen’s Kappa statistic. The Kaplan-Meier survival curve was plotted， and a survival analysis was performed using the log-rank test. ResultsThe prevalence rate of frailty assessed by FFP， LFI， and SPPB was 37.2%， 22.4%， and 20.2%， respectively， with a moderate consistency between FFP and LFI/SPPB （κ=0.57， 95% confidence interval ［CI］： 0.47 — 0.67； κ=0.51， 95%CI： 0.41 — 0.62） and a relatively high consistency between LFI and SPPB （κ=0.87， 95%CI： 0.80 — 0.94）. Compared with the non-frailty group， the frailty group had significantly higher all-cause mortality rate and incidence rate of composite endpoints （P0.001）. After multivariate adjustment， FFP， LFI， and SPPB had a hazard ratio of 2.42（95%CI： 1.51 — 5.11）， 2.21（95%CI： 1.11 — 4.42）， and 2.21（95%CI： 1.14 — 4.30）， respectively， in predicting all-cause mortality， as well as a hazard ratio of 2.51（95%CI： 1.61 — 3.91）， 2.40（95%CI： 1.51 — 3.80）， and 2.20（95%CI： 1.39 — 3.47）， respectively， in predicting composite endpoints. Compared with Child-Pugh score， FFP had a significantly greater area under the ROC curve （AUC） in predicting all-cause mortality （0.79 vs 0.69， P=0.032） and composite endpoints （0.75 vs 0.68， P=0.044）. Frailty assessment tools combined with Child-Pugh score significantly improved the performance in predicting all-cause mortality and composite endpoints， with an AUC of 0.81 — 0.82 and 0.77 — 0.78， respectively （P0.05）. NRI and IDI analyses further confirmed the improvement of the combined model in classification （all P0.001）. ConclusionFFP， LFI， and SPPB can independently predict adverse outcomes in patients with liver cirrhosis， among which FFP has the best predictive performance， and the combination of frailty assessment tools with Child-Pugh score can significantly enhance the accuracy of prognostic evaluation.

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral malignancies, with more than 370 000 new cases and approximately 188 000 deaths annually worldwide. In China, there are roughly 65 000 new cases and 35 000 deaths each year, showing a significant upward trend compared with 2015 statistics. Despite continuous advancements in treatment modalities, the 5-year survival rate remains stagnant at 50%-60%, where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology. To address these critical challenges, this study established a standardized bioban-king protocol for OSCC patient-derived organoids (PDOs) (Patent: Method for constructing an oral squamous cell carcinoma organoid bank, ZL202311378598.3). Through groundbreaking optimization of culture media, enzymatic digestion kinetics, and stepwise cryopreservation, we achieved a biobanking success rate exceeding 95% and pioneered synchronous cultivation of matched primary tumors, lymph node metastases, and adjacent normal mucosa from individual patients, preserving spatial heterogeneity and stromal interactions. Leveraging this platform, we developed high-throughput drug screening: Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate (ATP)-based viability assays; We discovered resistance mechanisms: Identified sialylated cancer IgG (SIA-cIgG)-mediated cis-platin resistance (primary/secondary) through PTPN13 suppression, with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy. Besides, we elucidated metastatic drivers: CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming, activating epithelial-mesenchymal plasticity (EMP) and inducing partial epithelial-mesenchymal transition (pEMT). This "holographic patient-mirroring" platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Technical Guidelines (Technical guideline for establishing patient-derived oral squamous cell carcinoma organoid banks, CHSA 2024-08). Future integration of immune-competent organoids, 3D-bioprinted vasculature, and multi-omics-AI systems will accelerate personalized oncology. These innovations will accelerate clinical translation of personalized therapeutic regimens, ultimately bridging the gap between bench research and bedside application.
Humans ; Organoids/pathology* ; Mouth Neoplasms/genetics* ; Carcinoma, Squamous Cell/pathology* ; Tissue Banks ; Biological Specimen Banks

BACKGROUND: Medical informatics accumulated vast amounts of data for clinical diagnosis and treatment. However, limited access to follow-up data and the difficulty in integrating data across diverse platforms continue to pose significant barriers to clinical research progress. In response, our research team has embarked on the development of a specialized clinical research database for cardiology, thereby establishing a comprehensive digital platform that facilitates both clinical decision-making and research endeavors. METHODS: The database incorporated actual clinical data from patients who received treatment at the Cardiovascular Medicine Department of Chinese PLA General Hospital from 2012 to 2021. It included comprehensive data on patients' basic information, medical history, non-invasive imaging studies, laboratory test results, as well as peri-procedural information related to interventional surgeries, extracted from the Hospital Information System. Additionally, an innovative artificial intelligence (AI)-powered interactive follow-up system had been developed, ensuring that nearly all myocardial infarction patients received at least one post-discharge follow-up, thereby achieving comprehensive data management throughout the entire care continuum for high-risk patients. RESULTS: This database integrates extensive cross-sectional and longitudinal patient data, with a focus on higher-risk acute coronary syndrome patients. It achieves the integration of structured and unstructured clinical data, while innovatively incorporating AI and automatic speech recognition technologies to enhance data integration and workflow efficiency. It creates a comprehensive patient view, thereby improving diagnostic and follow-up quality, and provides high-quality data to support clinical research. Despite limitations in unstructured data standardization and biological sample integrity, the database's development is accompanied by ongoing optimization efforts. CONCLUSION The cardiovascular specialty clinical database is a comprehensive digital archive integrating clinical treatment and research, which facilitates the digital and intelligent transformation of clinical diagnosis and treatment processes. It supports clinical decision-making and offers data support and potential research directions for the specialized management of cardiovascular diseases.

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

Objective: To observed the effect of a curcumin-based vaginal gel combined with electroporation for the treatment of vulvovaginal candidiasis (VVC) caused by Candida albicans. Methods: Temperature-sensitive in situ gels (ISG) were prepared using poloxamers 407 and 188 as matrices. The mass ratio of poloxamer 407 and poloxamer 188 was 7:1 with a gelation temperature of approximately 29°C and gelation time of 2.5 min. Results: Electroporation increased the transmucosal permeability of the model drug, doxorubicin and improved the antifungal effects of curcumin. In vitro antifungal experiments showed that the number of fungal colonies in curcumin ISG combined with electroporation was lower than that in pure curcumin ISG. In vivo pharmacodynamic experiments showed that, compared to the model group, curcumin ISG with electroporation inhibited the growth of C. albicans, alleviated vaginal mucosal edema, and reduced the inflammatory response. Conclusion Curcumin ISG combined with electroporation has substantial potential for the efficient clinical treatment of VVC.

Objective:The pregnancy outcome,related influencing factors and genetic results of pregnant women with intracranial cysts were comparatively analyzed to provide evidence for prenatal consultation and clini-cal treatment of the fetus with intracranial cyst.Methods:A total of 92 pregnant women with fetal intracranial cysts were selected.The data of pregnancy and delivery were collected by electronic medical record system.The prog-nosis of newborn was recorded by telephone follow-up.According to the pregnancy outcome,they were divided into continued pregnancy group(80/92,87%)and induced labor group(12/92,13%).Analyze the factors that might influence the pregnancy outcome of intracranial cysts,as well as genetic outcomes.Results:Compared with the continued pregnancy group and the induced labor group,there were statistical differences between the gesta-tion age at diagnosis≤28 weeks and the presence of other abnormalities(P＜0.05),but there were no statistical differences in the age of pregnant women and the number of intracranial cysts(P＞0.05).The results of genetic examination were compared between normal and abnormal groups of 25 cases,and there were no statistical differences in the age of pregnant women,the gestation age at diagnosis,whether there was adverse pregnancy history,whether there was single cyst,and the presence of other abnormalities(P＞0.05).Conclusions:Diagno-sis of fetal intracranial cyst at≤28 weeks gestation and other systemic abnormalities are risk factors affecting pregnancy outcome.

Objective:The pregnancy outcome,related influencing factors and genetic results of pregnant women with intracranial cysts were comparatively analyzed to provide evidence for prenatal consultation and clini-cal treatment of the fetus with intracranial cyst.Methods:A total of 92 pregnant women with fetal intracranial cysts were selected.The data of pregnancy and delivery were collected by electronic medical record system.The prog-nosis of newborn was recorded by telephone follow-up.According to the pregnancy outcome,they were divided into continued pregnancy group(80/92,87%)and induced labor group(12/92,13%).Analyze the factors that might influence the pregnancy outcome of intracranial cysts,as well as genetic outcomes.Results:Compared with the continued pregnancy group and the induced labor group,there were statistical differences between the gesta-tion age at diagnosis≤28 weeks and the presence of other abnormalities(P＜0.05),but there were no statistical differences in the age of pregnant women and the number of intracranial cysts(P＞0.05).The results of genetic examination were compared between normal and abnormal groups of 25 cases,and there were no statistical differences in the age of pregnant women,the gestation age at diagnosis,whether there was adverse pregnancy history,whether there was single cyst,and the presence of other abnormalities(P＞0.05).Conclusions:Diagno-sis of fetal intracranial cyst at≤28 weeks gestation and other systemic abnormalities are risk factors affecting pregnancy outcome.