OBJECTIVE: To investigate the effect of human adipose-derived mesenchymal stem cells (hASCs) exosomes on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) extracted from osteoporotic mice, and to evaluate the effect of hASCs exosomes on preventing bone loss induced by estrogen deficiency. METHODS: hASCs exosomes were extracted by ultracentrifugation. The osteoporotic mice were established by bilateral ovariectomy (OVX). BMSCs were isolated from osteo-porotic mice and cultured for further analysis. In the experimental group, these BMSCs were exposed to an osteogenic induction medium supplemented with hASCs exosomes to evaluate their potential effects on osteogenesis. In contrast, the control group was treated with the same osteogenic induction medium, but without the addition of hASCs exosomes, to serve as a baseline comparison for the study. To comprehensively assess the osteogenic differentiation of BMSCs influenced by hASCs exosomes, alkaline phosphatase (ALP) staining, ALP activity quantitative analysis and quantitative reverse transcription polymerase chain reaction (qPCR) were performed. These evaluations provided critical insights into the role of hASCs exosomes in promoting osteoblast differentiation and bone formation in osteoporotic conditions. The fluorescence labeled hASCs exosomes were injected via the tail vein to observe the biodistribution of exosomes. Two weeks after OVX, the mice were divided into three groups: The experimental group consisted of estrogen-deficient mice receiving hASCs exosome injections; the negative control group consisted of estrogen-deficient mice receiving phosphate-buffered saline (PBS) injections; and the positive control group consisted of mice that underwent Sham surgery and received PBS injections.The injections were administered once every 3 days, for a total of 8 injections. Afterward, the femurs were collected from the mice, and micro-computed tomography (micro-CT) was performed to measure bone mineral density and conduct bone morphometric analysis. RESULTS: hASCs exosomes were successfully extracted using ultracentrifugation. After the induction by hASCs exosomes, ALP staining and ALP activity in the BMSCs extracted from osteoporotic mice were significantly enhanced, the expression of osteogenesis related genes in BMSCs were significantly up-regulated. More trabecular bone and higher bone mineral density were observed in estrogen-deficient mice injected with hASCs exosomes compared with estrogen-deficient mice injected with PBS, and there was no significant decrease in bone mineral density compared with the Sham operation group. CONCLUSION hASCs exosomes promoted the osteogenic differentiation of BMSCs extracted from osteoporotic mice. hASCs exosomes prevented bone loss induced by estrogen deficiency.
Animals ; Mesenchymal Stem Cells/cytology* ; Exosomes ; Estrogens/deficiency* ; Humans ; Osteogenesis ; Cell Differentiation ; Female ; Mice ; Osteoporosis/prevention & control* ; Ovariectomy ; Adipose Tissue/cytology* ; Cells, Cultured

The shaoyang meridian is an important pivot between the internal organs and meridians system， with the functions of regulating qi and blood， balancing yin and yang， and coordinating the ascending and descending movement of qi. Dysfunction of the shaoyang pivot can lead to spleen and kidney deficiency， impaired liver and gallbladder qi regulation， and stagnation of qi and blood. It is believed that the onset and progression of Crohn's disease are closely related to shaoyang pivot dysfunction， with the core pathogenesis characterized by shaoyang disharmony， spleen deficiency， dampness retention， and blood stasis. Based on this understanding， the treatment principle centers on harmonizing the shaoyang pivot， supplemented by methods such as warming and nourishing the spleen and stomach， tonifying shaoyang， and soothing the liver and benefiting the gallbladder. Acupuncture is employed to target key acupoints along the shaoyang meridian to restore its regulatory functions， improve spleen and stomach transformation and transportation， facilitate liver and gallbladder qi flow， and promote the circulation of qi and blood. This provides a practical therapeutic approach for acupuncture-based treatment of Crohn's disease.

Objective:To explore the effect of preoperative gamma-glutamyl transferase to albumin ratio (GAR) on prognosis of patients with Barcelona clinic liver cancer (BCLC)stage 0-A hepatocellular carcinoma (HCC) after microwave ablation (MWA).Methods:The clinical data of 201 patients with BCLC stage 0 to A who underwent MWA at two centers of Jiaxing Second Hospital and Shengjing Hospital of China Medical University from January 2011 to December 2018 were retrospectively analyzed, including 152 males and 49 females, aged (57.5±9.6) years. X-tile software was used to divide patients into a low GAR group ( n=84, GAR<0.9) and a high GAR group ( n=117, GAR≥0.9). Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival comparison. Univariate and multivariate Cox regression analysis was used to evaluate the relationship between GAR and prognosis. Results:The cumulative survival rates at 1, 3 and 5 years postoperatively were 98.7%, 93.8%, 78.5% for the low GAR group, which were superior to that 97.2%, 87.1%, 70.2% for the high GAR group, and the difference was statistically significant ( χ2=11.89, P=0.001). The recurrence-free survival rates at 1, 3 and 5 years after surgery between the two groups was no significant difference ( χ2=1.70, P=0.192). Multivariate analysis revealed that high GAR ( HR=2.723, 95% CI: 1.508-4.914, P=0.001) was independent risk factors for overall survival after MWA in patients with BCLC stages 0 to A HCC. Male gender ( HR=1.959, 95% CI: 1.127-3.305, P=0.017) and tumor diameter ≥2 cm ( HR=1.547, 95% CI: 1.008-2.373, P=0.046) were independent risk factors for recurrence after MWA in patients with BCLC stages 0 to A HCC. Univariate analysis, GAR≥0.9 was not associated with postoperative recurrence ( HR=1.315, 95% CI: 0.869-1.989, P=0.195). Conclusion:Preoperative GAR (≥0.9) is an independent risk factor affecting overall survival in patients with BCLC stages 0 to A HCC after MWA.

With the increasing global recognition of Traditional Chinese Medicine (TCM), acupuncture, as a non-pharmacological treatment, has demonstrated promising potential in alleviating symptoms, improving quality of life, and modulating immune and neurological system functions in patients with Crohn's disease (CD). This review summarizes the theoretical foundations and recent research progress on acupuncture for CD, and introduces a personalized "Three Discriminations" diagnostic and therapeutic strategy based on syndrome differentiation, meridian differentiation, and acupoint selection. It also identifies the target patient populations and clinical application value of acupuncture in CD treatment. Despite preliminary progress, acupuncture treatment for CD still faces multiple challenges, including limited high-quality clinical research evidence, uneven resource distribution, non-standardized efficacy evaluation systems, insufficiently standardized treatment strategies, and an incomplete understanding of its underlying mechanisms. Future efforts should focus on establishing high-quality evidence systems, optimizing integrative treatment strategies combining acupuncture with conventional medicine, and conducting deep exploration of multi-dimensional mechanisms, with the goal of promoting the standardized integration of acupuncture into the management of CD and providing patients with safer, more precise, and sustainable therapeutic options.

Objective:To investigate the therapeutic value of visual endoscopic retrograde appendicitis therapy (vERAT) in pediatric patients with acute suppurative appendicitis (ASA).Methods:This was a retrospective cohort study. A total of 55 ASA patients who underwent vERAT at the Pediatric Department of the Tangdu Hospital of Air Force Medical University between November 2023 and January 2025 were selected and divided into groups based on the presence or absence of fecaliths: fecalith group and non-fecalith group. The baseline characteristics, initial treatment success rates, treatment costs, hospital stay duration, procedure time, and recurrence rates between two groups were compared. Mann-Whitney U test and χ2 test were used to evaluate group differences. Results:A total of 55 ASA patients were enrolled, including 38 males and 17 females, with the age of 11.2 (9.2, 13.1) years. Based on the presence of fecaliths, patients were divided into two groups: fecalith group (32 cases) and non-fecalith group (23 cases). No statistically significant differences were observed between the two groups in terms of age, gender, duration of abdominal pain, white blood cell count, neutrophil percentage, diameter of appendix, thickness of appendix clinical symptoms or signs (all P>0.05). The initial treatment success rates were 91% (29/32) in fecalith group and 96% (22/23) in non-fecalith group, with no statistically significant difference ( P=0.632). However, significant differences were noted in stent placement ( χ2=5.85, P=0.026) and procedure time ( Z=4.75, P<0.001). The follow-up duration time was 6.0 (2.0, 12.0) and 7.0 (2.0, 8.5) months for the fecalith and non-fecalith groups, respectively, with no significant difference ( Z=0.05, P=0.962). The recurrence rates were 14% (4/29) in fecalith group and 5% (1/22) in non-fecalith group, with no statistically significant difference ( P=0.375). Conclusions:vERAT can safely and effectively treat pediatric ASA, regardless of the presence or absence of fecaliths. It can provide a new treatment option for ASA.

Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.

A 71-year-old man with undifferentiated sarcoma was treated with palliative first-line regimen(epirubicin,anlotinib and penpulimab)for 6 cycles and maintained with anlotinib and penpulimab for 30 cycles.He was admitted to the hospital due to chest pain 25 months after the first treatment.The laboratory examination showed cardiac troponin T 1.26 ng·mL-1,N terminal pro B type natriuretic peptide 8,545 pg·mL-1,coronary computed tomography angiography(CTA)showed non-calcified plaque in the left proximal anterior descending branch,severe lumen stenosis,nearly complete occlusion.Emergency CTA was performed on the same day,showing 50％stenosis of the distal left main coronary artery(LMCA);95％stenosis of the left anterior descending(LAD)branch ostium,the LAD branch was medium-sized and showed no stenosis;50％stenosis of the left circumflex branch(LCx),and a cardiac stent was implanted into the LAD branch.The patient has recovered after coronary artery stent implantation.Naranjo's Assessment Scale was used to evaluate the association of suspected drugs,the acute myocardial infarction of this patient was likely associated with the combination of penpulimab and anlotinib.Myocardial infarction is a rare but severe adverse drug reaction of anti-tumor treatment.This article summarizes the related risks and treatment measures to provide a reference for clinical medication safety.

Objective To evaluate the effectiveness and safety of Su Fei He Ji combined with anlotinib hydrochloride in the treatment of refractory advanced non-small cell lung cancer(NSCLC)patients presenting with phlegm stasis obstructing lung type.Methods Thirty-nine patients with advanced NSCLC were randomly assigned to either a control group(19 patients)or an experimental group(20 patients).The control group received treatment with anlotinib alone,while the experimental group received an additional oral administration of Su Fei He Ji.A comparative analysis was conducted between the two groups based on various parameters including short-term objective therapeutic efficacy,progression-free survival,TCM syndrome scores,KPS scores,weight changes,related tumor markers,incidence of adverse reactions,and variations in plasma concentrations of anlotinib.Results Following treatment,the objective response rate was 5%and the disease control rate was 85%in the experimental group,while the control group showed an objective response rate of 0%and a disease control rate of 78.95%.No statistically significant difference was observed in short-term objective efficacy between the two groups(P>0.05).Notably,the experimental group exhibited a significant improvement compared to the control group in various aspects,including TCM syndrome scores and KPS scores(P<0.05).Conversely,no significant differences were observed in weight changes or the reduction levels of other tumor markers(CEA,SCC,CA125,CA199,CYFRA21-1)(P>0.05).Moreover,the incidence of fatigue was notably lower in the experimental group(P<0.05),while no statistical difference was evident in the occurrence of other adverse reactions,such as hypertension,rash,and bleeding,between the two groups(P>0.05).It is important to highlight that there was no statistically significant variance in plasma concentrations between the groups(P>0.05),and no significant correlation was identified between plasma concentrations and the incidence of adverse reactions(P>0.05).Conclusion The combination of Su Fei He Ji and anlotinib hydrochloride effectively improves clinical symptoms and quality of life,and reduces adverse reactions in advanced NSCLC patients.This is achieved without affecting the plasma concentrations of anlotinib.

Objective To develop a method for rapidly identifying Clostridioides difficile(C.difficile)and de-termining high-producing toxin strains,conduct clinical evaluation.Methods The loop-mediated isothermal amplifi-cation(LAMP)method was used to identify C.difficile based on the tcdC,tcdA,and tcdB genes.The sensitivi-ty,specificity,and overall consistency of the detection method were evaluated.Results Feces specimens from 499 hospitalized patients suspected of C.difficile-associated diarrhea were detected,with C.difficile detection rate of 12.8％(64/499),out of which the detection rate of toxin-producing C.difficile was 10.8％(54/499).The sensi-tivity,specificity,positive predictive value,and negative predictive value of the detection method for tcdA were 87.2％,98.9％,89.1％,and 98.6％,respectively,and 88.2％,99.6％,90.0％,and 98.73％for tcdB,respec-tively.The total toxin levels of different strains were different,but the average toxin production level of A+B+strains(1.79 μg/mL)was higher than those of A-B+strains(0.72 μg/mL)and A-B-strains(＜0.10 μg/mL).Conclusion The portable high-throughput LAMP detection method can rapidly and efficiently identify C.difficile and determine high-producing toxin strains.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.